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Sample records for hla-matched allogeneic peripheral

  1. Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

    Science.gov (United States)

    Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

    2017-03-01

    Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Analysis of the results of allogeneic hematopoietic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair

    Directory of Open Access Journals (Sweden)

    Ye. V. Kuzmich

    2015-01-01

    Full Text Available HLA matching of the donor / recipient pair is a major factor associated with the outcome of allogeneic stem cell transplantation. In the presentstudy we analyzed the risk of severe acute graft-versus-host disease, graft failure, 2.year overall survival of the patients after allogeneic stem cell transplantation depending on HLA matching of the unrelated donor / recipient pair.

  3. The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

    DEFF Research Database (Denmark)

    Michallet, M; Sobh, M; Milligan, D

    2010-01-01

    We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high...... worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings...... support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease....

  4. Influence of HLA Matching on the Efficacy of Allogeneic Mesenchymal Stromal Cell Therapies for Osteoarthritis and Degenerative Disc Disease

    Directory of Open Access Journals (Sweden)

    Javier García-Sancho, MD, PhD

    2017-09-01

    Conclusions. This lack of reactivity is presumably due to the cooperation of 2 factors, (1 downregulation of the host immune responses by the transplanted MSCs and (2 effective insulation of these cells inside the articular cavity or the intervertebral disc, respectively. Interestingly, better HLA matching did not enhance efficacy. These observations have medical relevance as they support the clinical use of allogeneic cells, at least as a single-dose administration. Multiple-dose applications will require further research to exclude possible sensitization.

  5. The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry.

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    Michallet, M; Sobh, M; Milligan, D; Morisset, S; Niederwieser, D; Koza, V; Ruutu, T; Russell, N H; Verdonck, L; Dhedin, N; Vitek, A; Boogaerts, M; Vindelov, L; Finke, J; Dubois, V; van Biezen, A; Brand, R; de Witte, T; Dreger, P

    2010-10-01

    We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high resolution ('well matched' unrelated donor, WMUD), and 139 were mismatched (MM), including 30 matched in low resolution; 266 patients (72%) received reduced-intensity conditioning and 102 (28%) received standard. According to the EBMT risk score, 11% were in scores 1-3, 23% in score 4, 40% in score 5, 22% in score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings support the use of WMUD as equivalent alternative to HLA-matched sibling donors for allogeneic HSCT in CLL, and justify the application of EBMT risk score in this disease.

  6. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype.

    Science.gov (United States)

    Hsieh, Matthew M; Fitzhugh, Courtney D; Weitzel, R Patrick; Link, Mary E; Coles, Wynona A; Zhao, Xiongce; Rodgers, Griffin P; Powell, Jonathan D; Tisdale, John F

    2014-07-02

    Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant. To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. From July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5-31.7 × 10(6) cells/kg) from human leukocyte antigen-matched siblings. The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell-thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing. Twenty-nine patients survived a median 3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and

  7. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia.

    NARCIS (Netherlands)

    Schrezenmeier, H.; Passweg, J.R.; Marsh, J.C.; Bacigalupo, A.; Bredeson, C.N.; Bullorsky, E.; Camitta, B.M.; Champlin, R.E.; Gale, R.P.; Fuhrer, M.; Klein, J.P.; Locasciulli, A.; Oneto, R.; Schattenberg, A.V.M.B.; Socie, G.; Eapen, M.

    2007-01-01

    We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic

  8. The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry.

    NARCIS (Netherlands)

    Michallet, M.; Sobh, M.; Milligan, D.; Morisset, S.; Niederwieser, D.; Koza, V.; Ruutu, T.; Russell, N.H.; Verdonck, L.; Dhedin, N.; Vitek, A.; Boogaerts, M.; Vindelov, L.; Finke, J.; Dubois, V.; Biezen, A. van; Brand, R.; Witte, T.J.M. de; Dreger, P.

    2010-01-01

    We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high

  9. The impact of HLA matching on long-term transplant outcome after allogeneic hematopoietic stem cell transplantation for CLL: a retrospective study from the EBMT registry

    DEFF Research Database (Denmark)

    Michallet, M; Sobh, M; Milligan, D

    2010-01-01

    We analyzed 368 chronic lymphocytic leukemia patients who underwent allogeneic hematopoietic stem cell transplantation reported to the EBMT registry between 1995 and 2007. There were 198 human leukocyte antigen (HLA)-identical siblings; among unrelated transplants, 31 were well matched in high re...

  10. A Comparative Reference Study for the Validation of HLA-Matching Algorithms in the Search for Allogeneic Hematopoietic Stem Cell Donors and Cord Blood Units

    Science.gov (United States)

    2016-08-15

    donors and cord blood units W. Bochtler1, L. Gragert2, Z. I. Patel3, J. Robinson3,4, D. Steiner5, J. A. Hofmann6, J. Pingel6, A. Baouz7, A. Melis8, J...cord blood units for individual patients is of primary importance. This challenging search process is routinely performed in a donor registry or cord...term ‘ donor ’ to refer to donors of HSCs from bone marrow or peripheral blood and cord blood units and the term ‘ donor registry’ shall include cord blood

  11. Allogeneic Peripheral Blood Stem Cell Harvest

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

  12. Preimplantation genetic diagnosis with HLA matching.

    Science.gov (United States)

    Rechitsky, Svetlana; Kuliev, Anver; Tur-Kaspa, Illan; Morris, Randy; Verlinsky, Yury

    2004-08-01

    Preimplantation genetic diagnosis (PGD) has recently been offered in combination with HLA typing, which allowed a successful haematopoietic reconstitution in affected siblings with Fanconi anaemia by transplantation of stem cells obtained from the HLA-matched offspring resulting from PGD. This study presents the results of the first PGD practical experience performed in a group of couples at risk for producing children with genetic disorders. These parents also requested preimplantation HLA typing for treating the affected children in the family, who required HLA-matched stem cell transplantation. Using a standard IVF procedure, oocytes or embryos were tested for causative gene mutations simultaneously with HLA alleles, selecting and transferring only those unaffected embryos, which were HLA matched to the affected siblings. The procedure was performed for patients with children affected by Fanconi anaemia (FANC) A and C, different thalassaemia mutations, Wiscott-Aldrich syndrome, X-linked adrenoleukodystrophy, X-linked hyperimmunoglobulin M syndrome and X-linked hypohidrotic ectodermal displasia with immune deficiency. Overall, 46 PGD cycles were performed for 26 couples, resulting in selection and transfer of 50 unaffected HLA-matched embryos in 33 cycles, yielding six HLA-matched clinical pregnancies and the birth of five unaffected HLA-matched children. Despite the controversy of PGD use for HLA typing, the data demonstrate the usefulness of this approach for at-risk couples, not only to avoid the birth of affected children with an inherited disease, but also for having unaffected children who may also be potential HLA-matched donors of stem cells for treatment of affected siblings.

  13. GVHD after HLA-matched sibling BMT or PBSCT: Comparison of North American Caucasian and Japanese Populations

    Science.gov (United States)

    Kanda, Junya; Brazauskas, Ruta; Hu, Zhen-Huan; Kuwatsuka, Yachiyo; Nagafuji, Koji; Kanamori, Heiwa; Kanda, Yoshinobu; Miyamura, Koichi; Murata, Makoto; Fukuda, Takahiro; Sakamaki, Hisashi; Kimura, Fumihiko; Seo, Sachiko; Aljurf, Mahmoud; Yoshimi, Ayami; Milone, Giuseppe; Wood, William A; Ustun, Celalettin; Hashimi, Shahrukh; Pasquini, Marcelo; Bonfim, Carmem; Dalal, Jignesh; Hahn, Theresa; Atsuta, Yoshiko; Saber, Wael

    2016-01-01

    The risk of acute graft-versus-host disease (GVHD) after HLA-matched sibling bone marrow (BM) transplantation is lower in Japanese than in Caucasian patients. However, race may have differential effect on GVHD dependent on the graft source. North American Caucasian and Japanese patients receiving their first allogeneic BM or peripheral blood stem cell (PBSC) transplantations from an HLA-matched sibling for leukemia were eligible. BM was used in 13% and 53% of Caucasian and Japanese patients, respectively. In multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that graft source does not affect the impact of race on outcomes. The risk of grades III–IV acute GVHD was significantly lower in Japanese than in Caucasian patients (hazard ratio (HR) 0.74, 95% confidence interval (CI) 0.57–0.96), which resulted in lower risk of non-relapse mortality in Japanese patients (HR 0.69, 95% CI 0.54–0.89). The risk of relapse was also lower in this group. Lower risk of non-relapse mortality and relapse resulted in lower overall mortality rates among Japanese patients. In conclusion, irrespective of graft source, the risk of severe acute GVHD is lower in Japanese patients, which results in lower risk of non-relapse mortality. PMID:26762681

  14. HLA matching in unrelated donor bone marrow transplantation.

    Science.gov (United States)

    Charron, D J

    1996-11-01

    The availability of an HLA-matched sibling donor in only 30% to 35% of patients requiring allogeneic bone marrow transplantation (BMT) has led to the proposal of unrelated donors as an alternative source of bone marrow. The greater HLA incompatibility, which, although present, was undetected until recently in many unrelated donor BMT cases, has resulted in a higher rate of posttransplant complications and impaired acturial survival when compared with HLA-matched sibling BMT. Molecular HLA typing enables us to evaluate the impact of incompatibility at each locus in the outcome of unrelated donor BMT. The overall retrospective data would recommend that HLA-A, -B and -C allelic molecular matching should be implemented in addition to HLA-DR allelic matching. Further retrospective analysis is needed in order to assess which incompatibility or combinations are better tolerated than others. Only the definitive knowledge at the sequence level of the donor and the recipient HLA allelic diversity involved in controlling the allogeneic immune response will allow us to understand the precise biologic rationale of the graft-versus-host disease. Knowledge and control of the HLA incompatibilities should allow us to offset the detrimental effects of histoincompatibility while developing strategies to take advantage of the beneficial graft-versus-leukemia effect. Also the role of minor histocompatibility antigens remains largely unknown and will require careful evaluation before minor antigens can be used as a selection criterion in BMT. Carefully designed prospective studies will enable us to test the impact of each HLA locus. HLA typing and BMT represent a successful example of productive cooperation between basic and clinical sciences that should be pursued for the improvement of the clinical outcome of unrelated donor BMT.

  15. Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

    Science.gov (United States)

    2017-10-25

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Lymphoblastic Lymphoma; Myelodysplastic Syndrome With Excess Blasts; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome With Excess Blasts-2; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Refractory Acute Lymphoblastic Leukemia; Refractory Acute Myeloid Leukemia

  16. HLA-Matched Sibling versus Unrelated versus Haploidentical Related Donor Allogeneic Hematopoietic Stem Cell Transplantation for Patients Aged Over 60 Years with Acute Myeloid Leukemia: A Single-Center Donor Comparison.

    Science.gov (United States)

    Devillier, Raynier; Legrand, Faezeh; Rey, Jérôme; Castagna, Luca; Fürst, Sabine; Granata, Angela; Charbonnier, Aude; Harbi, Samia; d'Incan, Evelyne; Pagliardini, Thomas; Faucher, Catherine; Lemarie, Claude; Saillard, Colombe; Calmels, Boris; Mohty, Bilal; Maisano, Valerio; Weiller, Pierre-Jean; Chabannon, Christian; Vey, Norbert; Blaise, Didier

    2018-02-12

    Haploidentical related donor (HRD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) was developed as a valid option for the treatment of acute myeloid leukemia (AML) in the absence of a matched donor. However, many investigators are reluctant to consider the use of this alternative in elderly patients, anticipating high morbidity. Here, we report a single-center comparison of HRD versus matched sibling donor (MSD) and unrelated donor (UD) allo-HSCT for patients with AML aged ≥60 years. Ninety-four patients (MSD: n = 31; UD: n = 30; HRD: n = 33) were analyzed. The median age was 65 (range, 60 to 73) years. We observed a higher cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) after UD allo-HSCT (MSD versus UD versus HRD: 3% versus 33% versus 6%, respectively; P = .006). Two-year cumulative incidence of moderate or severe chronic GVHD was 17%, 27%, and 16% in the MSD, UD, and HRD groups, respectively (P = .487). No difference was observed in the 2-year cumulative incidence of relapse or nonrelapse mortality (NRM) (relapse: MSD versus UD versus HRD: 32% versus 25% versus 25%, respectively; P = .411; NRM: MSD versus UD versus HRD: 19% versus 27% versus 24%, respectively; P = .709). At 2 years, progression-free survival, overall survival, and GVHD- and relapse-free survival were 48%, 50%, and 39%, respectively, in the MSD group; 48%, 51%, and 23%, respectively, in the UD group; and 50%, 52%, and 32%, respectively, in the HRD group, without statistically significant differences between the groups. We conclude that HRD allo-HSCT is highly feasible and no less efficient than MSD or UD allo-HSCT in patients with AML aged ≥60 years. Thus, the absence of a HLA-identical donor should not limit the consideration of allo-HSCT for the treatment of AML. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide.

    Science.gov (United States)

    Kanakry, Christopher G; Bolaños-Meade, Javier; Kasamon, Yvette L; Zahurak, Marianna; Durakovic, Nadira; Furlong, Terry; Mielcarek, Marco; Medeot, Marta; Gojo, Ivana; Smith, B Douglas; Kanakry, Jennifer A; Borrello, Ivan M; Brodsky, Robert A; Gladstone, Douglas E; Huff, Carol Ann; Matsui, William H; Swinnen, Lode J; Cooke, Kenneth R; Ambinder, Richard F; Fuchs, Ephraim J; de Lima, Marcos J; Andersson, Borje S; Varadhan, Ravi; O'Donnell, Paul V; Jones, Richard J; Luznik, Leo

    2017-03-09

    The intensive and prolonged immunosuppressive therapy required to prevent or treat graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT) puts patients at substantial risk for life-threatening infections, organ toxicity, and disease relapse. Posttransplantation cyclophosphamide (PTCy) can function as single-agent GVHD prophylaxis after myeloablative, HLA-matched related (MRD), or HLA-matched unrelated (MUD) donor T-cell-replete bone marrow allografting, obviating the need for additional prophylactic immunosuppression. However, patients who develop GVHD require supplemental treatment. We assessed the longitudinal requirement for immunosuppressive therapy in 339 patients treated with this transplantation platform: 247 receiving busulfan/cyclophosphamide (BuCy) conditioning (data collected retrospectively) and 92 receiving busulfan/fludarabine (BuFlu) conditioning (data collected prospectively). Approximately 50% of MRD patients and 30% of MUD patients never required immunosuppression beyond PTCy. In patients requiring further immunosuppression, typically only 1 to 2 agents were required, and the median durations of systemic pharmacologic immunosuppression for the BuCy MRD, BuFlu MRD, BuCy MUD, and BuFlu MUD groups all were 4.5 to 5 months. For these 4 groups, 1-year probabilities of being alive and off all systemic immunosuppression were 61%, 53%, 53%, and 51% and 3-year probabilities were 53%, 48%, 49%, and 56%, respectively. These data suggest that PTCy minimizes the global immunosuppressive burden experienced by patients undergoing HLA-matched alloBMT.

  18. PBSCT is associated with poorer survival and increased chronic GvHD than BMT in Japanese paediatric patients with acute leukaemia and an HLA-matched sibling donor.

    Science.gov (United States)

    Shinzato, Aki; Tabuchi, Ken; Atsuta, Yoshiko; Inoue, Masami; Inagaki, Jiro; Yabe, Hiromasa; Koh, Katsuyoshi; Kato, Koji; Ohta, Hideaki; Kigasawa, Hisato; Kitoh, Toshiyuki; Ogawa, Atsushi; Takahashi, Yoshiyuki; Sasahara, Yoji; Kato, Shun-Ichi; Adachi, Souichi

    2013-09-01

    Peripheral blood stem cells (PBSC) may be used as an alternative to bone marrow (BM) for allogeneic transplantation. Since peripheral blood stem cell bank from unrelated volunteer donor has been started in Japan, use of PBSC allografts may be increased. Therefore we surveyed the outcomes of Japanese leukemia children after PBSC and BM transplantation. This retrospective study compared the outcomes of 661 children (0-18 years) with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) who received their first allogeneic peripheral blood stem cell transplantation (PBSCT; n = 90) or bone marrow transplantation (BMT; n = 571) from HLA-matched siblings between January 1996 and December 2007. Neutrophil recovery was faster after PBSCT than after BMT (ALL: P vs. 9.9%, P = 0.0066; AML: 41.6% vs. 11.1%, P vs. 57.1%, P = 0.0257). The 5-year overall survival (OS) was lower after PBSCT than after BMT for ALL (42.4% vs. 63.7%, P = 0.0032) and AML (49.8% vs. 71.8%, P = 0.0163). Multivariate analysis revealed the use of PBSC was a significant risk factor for DFS and OS. PBSCT and BMT did not differ in relapse rate, acute GvHD for ALL and AML, or in DFS for AML. PBSC allografts in Japanese children engraft faster but are associated with poorer survival and increased chronic GvHD. Copyright © 2013 Wiley Periodicals, Inc.

  19. Comparative analysis of unrelated cord blood transplantation and HLA-matched sibling hematopoietic stem cell transplantation in children with high-risk or advanced acute leukemia.

    Science.gov (United States)

    Zheng, Changcheng; Zhu, Xiaoyu; Tang, Baolin; Yao, Wen; Song, Kaidi; Tong, Juan; Geng, Liangquan; Liu, Huilan; Sun, Zimin

    2015-03-01

    The aim of this report was to present a clinical comparison of unrelated cord blood transplantation (CBT) and human leukocyte antigen (HLA)-matched sibling allogeneic peripheral blood stem cell or bone marrow transplantation (allo-PBSCT/BMT) in children with high-risk or advanced acute leukemia. A total of 115 consecutive pediatric patients received unrelated CBT (n = 90) or sibling allo-PBSCT/BMT (n = 25) between 2000 and 2012. Neutrophil and platelet recovery were significantly delayed after CBT compared to allo-PBSCT/BMT. There was no difference in the incidence of acute graft-versus-host disease (GVHD) or chronic GVHD between the two groups. The cumulative incidence of transplant-related mortality (TRM) was higher in the CBT group than in the allo-PBSCT/BMT group (32.5 vs 12.8 %) (p = 0.03). The cumulative incidence of relapse was 13.1 % after CBT, which was significantly lower than that of after allo-PBSCT/BMT (45.3 %) (p = 0.015). The overall survival (OS) and leukemia-free survival (LFS) in the CBT group were similar to those of the allo-PBSCT/BMT group; however, for acute myeloid leukemia (AML) patients, the 5-year LFS in the CBT group was slightly better than the allo-PBSCT/BMT group (55.7 % for CBT and 32.7 % for allo-PBSCT/BMT) (p = 0.08). Our comparisons suggest that for high-risk or advanced childhood acute leukemia, unrelated CBT has a higher TRM and similar long-term survival, but better antileukemia effect than HLA-matched sibling PBSCT/BMT. New strategies and better supportive care are required to decrease the TRM of CBT.

  20. Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

    International Nuclear Information System (INIS)

    Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

    2010-01-01

    A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

  1. Lichen Striatus Occurring after Allogenic Peripheral Blood Stem Cell Transplantation in an Adult with Aplastic Anemia

    OpenAIRE

    Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2012-01-01

    Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which w...

  2. Allogeneic human dermal fibroblasts are viable in peripheral blood mononuclear co-culture

    Directory of Open Access Journals (Sweden)

    Restu Syamsul Hadi

    2014-08-01

    Full Text Available Background Transplanted allogeneic dermal fibroblasts retain stem cell subpopulations, and are easily isolated, expanded and stored using standard techniques. Their potential for regenerative therapy of chronic wounds should be evaluated. The aim of this study was to determine allogeneic fibroblast viability in the presence of peripheral blood mononuclear cells (PBMC. Methods In this experimental study, fibroblasts were isolated from foreskin explants, expanded in the presence of serum, and stored using slow-freezing. We used one intervention group of allogeneic fibroblasts co-cultured with PBMC and 2 control groups of separate fibroblast and PBMC cultures.Fibroblasts were characterized by their collagen secretion and octamer-binding transcription factor 4 (OCT4 expression. Viability was evaluated using water soluble tetrazolium-1 (WST-1 proliferation assay. Absorbances were measured at 450 nm. Data analysis was performed by student’s paired t-test. Results Dermal fibroblasts were shown to secrete collagen, express OCT4, be recoverable after cryopreservation, and become attached to the culture dish in a co-culture with PBMC. Co-cultured and control fibroblasts had no significantly different cell viabilities (p>0.05. Calculated viable cell numbers increased 1.8 and 5.1-fold, respectively, at days 2 and 4 in vitro. Both groups showed comparable doubling times at days 2 and 4 in vitro. PBMC did not interfere with allogeneic fibroblast viability and proliferative capacity Conclusions Allogeneic fibroblasts remain viable and proliferate in the presence of host PBMC. Future research should evaluate allogeneic human dermal fibroblast competency in clinical settings. Dermal fibroblasts are a potential source for cell therapy in chronic wound management.

  3. Lichen striatus occurring after allogenic peripheral blood stem cell transplantation in an adult with aplastic anemia.

    Science.gov (United States)

    Mun, Je-Ho; Park, Hyun-Je; Kim, Hoon-Soo; Kim, Su-Han; Ko, Hyun-Chang; Kim, Byung-Soo; Kim, Moon-Bum

    2012-02-01

    Lichens striatus (LS) is an acquired, self-limiting inflammatory dermatosis that follows the lines of Blaschko. The etiology of the eruption is unknown, but several theories have been proposed with focus on environmental factors, viral infection, cutaneous injury, hypersensitivity, and genetic predisposition. We describe a 19-year-old woman who developed a unilateral linear eruption 17 months after allogenic peripheral blood stem cell transplantation. Histopathology revealed features, which were consistent with LS. To the best of our knowledge, our patient is the first case describing the appearance of LS occurring after allogenic stem cell transplantation. We speculate that this condition represents an unusual form of localized, chronic graft-versus-host disease.

  4. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

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    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

  5. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

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    Rehan Mujeeb Faridi

    Full Text Available Allogeneic hematopoietic cell transplantation (HCT can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT.The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs and 'validation' (146 pairs cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD, chronic GVHD needing systemic therapy (cGVHD and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS, cGVHD & relapse free survival (cGRFS and overall survival (OS] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17 and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11. High incidence of cGVHD associated with KIR genotype mismatching was

  6. Donor-Recipient Matching for KIR Genotypes Reduces Chronic GVHD and Missing Inhibitory KIR Ligands Protect against Relapse after Myeloablative, HLA Matched Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Faridi, Rehan Mujeeb; Kemp, Taylor J; Dharmani-Khan, Poonam; Lewis, Victor; Tripathi, Gaurav; Rajalingam, Raja; Daly, Andrew; Berka, Noureddine; Storek, Jan; Masood Khan, Faisal

    2016-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for many hematologic diseases. However, complications such as graft-versus-host disease (GVHD) and relapse of primary malignancy remain significant and are the leading causes of morbidity and mortality. Effects of killer Ig-like receptors (KIR)-influenced NK cells on HCT outcomes have been extensively pursued over the last decade. However, the relevance of the reported algorithms on HLA matched myeloablative HCT with rabbit antithymocyte globulin (ATG) is used for GVHD prophylaxis remains elusive. Here we examined the role of KIR and KIR-ligands of donor-recipient pairs in modifying the outcomes of ATG conditioned HLA matched sibling and unrelated donor HCT. The study cohort consisted of 281 HLA matched sibling and unrelated donor-recipient pairs of first allogeneic marrow or blood stem cell transplantation allocated into 'discovery' (135 pairs) and 'validation' (146 pairs) cohorts. High resolution HLA typing was obtained from the medical charts and KIR gene repertoires were obtained by a Luminex® based SSO method. All surviving patients were followed-up for a minimum of two years. KIR and HLA class I distributions of HCT pairs were stratified as per applicable definitions and were tested for their association with cause specific outcomes [acute GVHD grade II-IV (aGVHD), chronic GVHD needing systemic therapy (cGVHD) and relapse] using a multivariate competing risks regression model as well as with survival outcomes [relapse-free survival (RFS), cGVHD & relapse free survival (cGRFS) and overall survival (OS)] by multivariate Cox proportional hazards regression model. A significant association between KIR genotype mismatching (KIR-B/x donor into KIR-AA recipient or vice versa) and cGVHD was found in both discovery (p = 0.001; SHR = 2.78; 95%CI: 1.50-5.17) and validation cohorts (p = 0.005; SHR = 2.61; 95%CI: 1.33-5.11). High incidence of cGVHD associated with KIR genotype mismatching was applicable

  7. Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies

    International Nuclear Information System (INIS)

    Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Farzana, T.; Kahlid, M.Z.; Panwani, V.K.; Baig, M.I.; Shakoor, N.

    2004-01-01

    Objective: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematogical malignancies in Pakistan. Patients and Methods: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. Results: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10/sup 9/I was 10 days (range 8 -12 days) and platelet count of > 20 x 10/sup 9/1 was 14 days (12-17 days). Acute graft versus host disease (aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. Conclusion: Haematopoietic stem cell transplant

  8. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study.

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    Güngör, Tayfun; Teira, Pierre; Slatter, Mary; Stussi, Georg; Stepensky, Polina; Moshous, Despina; Vermont, Clementien; Ahmad, Imran; Shaw, Peter J; Telles da Cunha, José Marcos; Schlegel, Paul G; Hough, Rachel; Fasth, Anders; Kentouche, Karim; Gruhn, Bernd; Fernandes, Juliana F; Lachance, Silvy; Bredius, Robbert; Resnick, Igor B; Belohradsky, Bernd H; Gennery, Andrew; Fischer, Alain; Gaspar, H Bobby; Schanz, Urs; Seger, Reinhard; Rentsch, Katharina; Veys, Paul; Haddad, Elie; Albert, Michael H; Hassan, Moustapha

    2014-02-01

    In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m(2) [infants HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. 56 patients (median age 12·7 years; IQR 6·8-17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14-39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16-22) for neutrophils and 21 days (IQR 16-25) for platelets. At median follow-up of 21 months (IQR 13-35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86·46-99·09) and of EFS was 91% (79·78-96·17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III-IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (≥90%) myeloid

  9. Comparison of Amicus and COBE Spectra for allogenic peripheral blood stem cell harvest: Study from tertiary care centre in India.

    Science.gov (United States)

    Setia, Rasika Dhawan; Arora, Satyam; Handoo, Anil; Dadu, Tina; Choudhary, Dharma; Sharma, Sajeev Kumar; Kharya, Gaurav; Khandelwal, Vipin; Sachdeva, Prerna; Doval, Divya; Bakliwal, Anamika; Kapoor, Meenu; Bajaj, Shalu; Bachchas, Virendra; Singh, Praveen

    2017-06-01

    Most common source of stem cell graft for both autologous and allogenic haematopoietic transplants are peripheral blood haematopoietic progenitor stem cells. Adequate collection of the CD34+ cells and safety of the allogenic donor during the leukapheresis are of prime importance to an apheresis physician. Our retrospective analysis is a comparison between of two platforms namely, COBE Spectra and Amicus, for CD34+ mononuclear cell collection. The study included the data of GSCF (Granulocyte-Colony-Stimulating Factor) mobilized allogenic PBSC collections at our centre from January 2015 to June 2016. The apheresis platforms used were COBE Spectra and Amicus. Blood cell counts were done using LH750 Beckman Coulter (Florida, Miami, USA). CD45+ & CD34+ cell counts were done using BD FACS Canto-II Flow-Cytometer by ISHAGE guidelines. A total of 170 PBSC (100 COBE Spectra & 70 Amicus) harvests were done on 143 donors, of which 116 completed the collection in a single session and 27 required a second session. Demographic details and pre harvest peripheral blood counts for both the groups did not show any statistical differences. Amicus processed higher blood volume with higher ACD exposure and procedure time compared to COBE Spectra. Higher platelets loss was with COBE Spectra harvests with higher product volumes collection. Collection efficiency (CE2), collection ratio, CD34+ cells dose was similar on both the platforms. RBC contamination, absolute lymphocyte and monocytes counts were significantly higher with Amicus harvest product compared with COBE Spectra. A total of 14 (8.2%; citrate toxicity) adverse reactions were reported out of 170 allogenic PBSC collections. Our study suggests that both Amicus and COBE Spectra platforms offer comparable results for allogenic PBSC collections. Amicus offers a concentrated PBSC product with lesser volume and platelets loss but higher RBC contamination. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Impact of Autologous and Allogeneic Stem Cell Transplantation in Peripheral T-Cell Lymphomas

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    Peter Reimer

    2010-01-01

    Full Text Available Peripheral T/NK-cell lymphomas (PTCLs are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year.

  11. Impact of a Low CD34+ Cell Dose on Allogeneic Peripheral Blood Stem Cell Transplantation.

    Science.gov (United States)

    Yamamoto, Chihiro; Ogawa, Hiroyasu; Fukuda, Takahiro; Igarashi, Aiko; Okumura, Hirokazu; Uchida, Naoyuki; Hidaka, Michihiro; Nakamae, Hirohisa; Matsuoka, Ken-Ichi; Eto, Tetsuya; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-01

    Although the CD34 + cell dose in allogeneic peripheral blood stem cell transplantation (PBSCT) is considered to be associated with transplantation outcomes, a lower acceptable threshold has not been defined. We retrospectively analyzed 2919 adult patients with hematologic malignancies who underwent related PBSCT in Japan between 2001 and 2014. According to the number of CD34 + cells in the graft, we categorized 2494 patients in the standard group (2 to 5 × 10 6 cells/kg), 377 patient in the low group (1 to 2 × 10 6 cells/kg), and 48 patients in the very low group (<1 × 10 6 cells/kg). Compared with the standard group, the low and very low groups showed delayed neutrophil recovery (93.8%, 89.5%, and 78.3%, respectively at day +28; P < .001) and platelet recovery (69.3%, 53.0%, and 45.5%, respectively at day +28; P < .001). The 2-year overall survival (OS) in the 3 groups was 45.5%, 45.3%, and 29.8%, respectively, with inferior survival in the very low group. However, a higher percentage of high-risk patients may account for the inferior survival in the very low group, and no significant difference in OS was found in a multivariate analysis. There were no differences in relapse, nonrelapse mortality, or the development of graft-versus-host disease among the 3 groups. In conclusion, allogeneic PBSCT with low CD34 + cell doses of 1 to 2 × 10 6 cells/kg gives acceptable results, whereas further investigations are needed to evaluate the effects of lower doses of <1 × 10 6 cells/kg owing to the smaller number and the higher percentage of patients with adverse prognostic factors in this cohort. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Does a kidney-sharing alliance have to sacrifice cold ischemic time for better HLA matching?

    Science.gov (United States)

    Oniscu, Gabriel C; Plant, William; Pocock, Phil; Forsythe, John L R

    2002-05-27

    The Scotland-Northern Ireland Kidney Allocation Alliance was created in August 1998. The purpose was to optimize the transplant service through increased regional exchange, higher quality matched kidneys, and better organ distribution. An analysis was performed on prospectively collected data regarding retrieval and transplant activity. The degree of HLA matching, the cold ischemic time (CIT), the balance of exchange, and graft survival were analyzed for a 2-year period after the introduction of the new alliance and compared with the last year before alliance. There was a 17.7% increase in the number of transplants performed. In the 2-year period, 78% of kidneys were exported from the retrieving center compared with 55% in the prealliance year, (Pexchanged within the Alliance (P>0.05, Student's t test). The largest center was a net importer of kidneys, whereas small and medium-sized centers balanced their exchange within the 2-year period. The 1-year transplant survival rate improved from 81.5% in the prealliance year to 88.4% at the end of the second year. The introduction of a regional kidney allocation alliance has improved the degree of HLA matching and increased the exchange of organs, without a significant increase in the CIT and any detrimental effect on graft survival.

  13. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras

  14. Comparisons Between Allogeneic Peripheral Blood Stem Cell Transplantation and Allogeneic Bone Marrow Transplantation in Adult Hematologic Disease: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Yi-Chang Liu

    2003-11-01

    Full Text Available This retrospective study compared the outcomes in 32 adult patients with hematologic diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome, severe aplastic anemia who received allogeneic bone marrow transplantation (BMT, n = 14; median age, 28 years or allogeneic peripheral blood stem cell transplantation (PBSCT, n = 18; median age, 29 years from human leukocyte antigen-identical sibling donors. Median follow-up was 58 months in BMT recipients and 18 months in PBSCT recipients. Neutrophil (median, Day 8 vs Day 13, p < 0.001 and platelet engraftment (median, Day 9 vs Day 17, p < 0.001 was faster in the PBSCT group than in the BMT group. Patients receiving PBSCT required less platelet transfusion than those receiving BMT (median, 54 units vs 144 units, p < 0.001, but there was no significant difference in red cell transfusion. At 100 days, there was no difference in the incidence of acute graft-versus-host disease (GVHD (42.9% vs 33.3%, p = 0.72 or grade II-IV acute GVHD (14.3% vs 5.6%, p = 0.57, and there was no difference in the cumulative incidence of chronic GVHD (20% vs 33.3%, p = 0.67. No chronic GVHD was noted in any relapsed patients (BMT, 5; PBSCT, 3, and no patients with chronic GVHD during follow-up had a relapse. Relapse was the most frequent cause of death in both groups (BMT, 5/9, 55.6%; PBSCT, 3/4, 75%; p = 0.25; all relapses occurred within 1 year after transplantation. Overall survival was significantly better in the PBSCT group (35.7% vs 77.8%, p = 0.029, but this difference was lost if only hematologic malignancies were analyzed (30.8% vs 63.6%, p = 0.20. Our results are similar to those reported previously, with faster neutrophil and platelet engraftment and less severe acute GVHD and extensive chronic GVHD with PBSCT. Allogeneic PBSCT is a feasible and beneficial alternative to allogeneic BMT in adult hematologic disease.

  15. Experimental study on therapy of acute radiation sickness with transplantation of allogeneic peripheral blood hemopoietic stem cells

    International Nuclear Information System (INIS)

    Ma Enpu; Bi Jianjin; Zhan Aiqin

    1995-01-01

    In the study, 10 beagles were used. All the dogs were irradiated with 6.5 Gy of γ-rays from a 60 Co source (dose rate, 95.6-107.9 R/min) and divided into three groups. All the three dogs in the control group died, having survived 7.5 days on the average after irradiation. In the second group, four dogs were transplanted with allogeneic peripheral blood hemopoietic stem cells (PBHSC) without removing T lymphocytes. The results of sex chromosome tests after irradiation and transplantation showed that the cells were of donor type. All the four dogs died of severe graft versus-host disease (GVHD) and survived 41.6 days on the average after irradiation. In the third group, three dogs received transplantation of allogeneic PBHSC without T lymphocytes. Two of them died, and the third developed mild GVHD and survived over 4 years

  16. HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry

    Science.gov (United States)

    Gragert, Loren; Eapen, Mary; Williams, Eric; Freeman, John; Spellman, Stephen; Baitty, Robert; Hartzman, Robert; Rizzo, J. Douglas; Horowitz, Mary; Confer, Dennis; Maiers, Martin

    2018-01-01

    Background Hematopoietic stem-cell transplantation (HSCT) is a potentially lifesaving therapy for several blood cancers and other diseases. For patients without a suitable related HLA-matched donor, unrelated-donor registries of adult volunteers and banked umbilical cord–blood units, such as the Be the Match Registry operated by the National Marrow Donor Program (NMDP), provide potential sources of donors. Our goal in the present study was to measure the likelihood of finding a suitable donor in the U.S. registry. Methods Using human HLA data from the NMDP donor and cord-blood-unit registry, we built population-based genetic models for 21 U.S. racial and ethnic groups to predict the likelihood of identifying a suitable donor (either an adult donor or a cord-blood unit) for patients in each group. The models incorporated the degree of HLA matching, adult-donor availability (i.e., ability to donate), and cord-blood-unit cell dose. Results Our models indicated that most candidates for HSCT will have a suitable (HLA-matched or minimally mismatched) adult donor. However, many patients will not have an optimal adult donor — that is, a donor who is matched at high resolution at HLA-A, HLA-B, HLA-C, and HLA-DRB1. The likelihood of finding an optimal donor varies among racial and ethnic groups, with the highest probability among whites of European descent, at 75%, and the lowest probability among blacks of South or Central American descent, at 16%. Likelihoods for other groups are intermediate. Few patients will have an optimal cord-blood unit — that is, one matched at the antigen level at HLA-A and HLA-B and matched at high resolution at HLA-DRB1. However, cord-blood units mismatched at one or two HLA loci are available for almost all patients younger than 20 years of age and for more than 80% of patients 20 years of age or older, regardless of racial and ethnic background. Conclusions Most patients likely to benefit from HSCT will have a donor. Public investment in

  17. Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia.

    Science.gov (United States)

    Ebens, Christen L; DeFor, Todd E; Tryon, Rebecca; Wagner, John E; MacMillan, Margaret L

    2018-04-01

    Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic hematopoietic cell transplantation (HCT) for cure. With the evolution of conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD-HCT; n = 17) and AD-HCT (n = 57) performed for FA-associated SAA at a single institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD-HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD) was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was 0 versus 7%, with no statistically significant differences by type of transplant. The use of UCB was associated with decreased rates of neutrophil recovery in AD-HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher serious infection density before day +100 post-HCT was observed in AD-HCT compared with MSD-HCT (P = .02). These data demonstrate that AD-HCT should be considered at the same time as MSD-HCT for patients with FA-associated SAA. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction.

    Science.gov (United States)

    Walton, D C; Hiho, S J; Cantwell, L S; Diviney, M B; Wright, S T; Snell, G I; Paraskeva, M A; Westall, G P

    2016-09-01

    Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Alternative allogeneic donor sources for transplantation for childhood diseases: unrelated cord blood and haploidentical family donors.

    Science.gov (United States)

    Cairo, Mitchell S; Rocha, Vanderson; Gluckman, Eliane; Hale, Gregory; Wagner, John

    2008-01-01

    Allogeneic stem cell transplantation has been demonstrated to be curative in a wide variety of pediatric malignant and nonmalignant diseases, and can be traced back over 50 years ago to the original report of Thomas et al. HLA matched sibling donors have been the gold standard for pediatric recipients requiring allogeneic donors for both nonmalignant and malignant conditions. However, only 25% of potential pediatric recipients possesses an HLA-matched sibling donor, and the frequency is even less in those with genetic nonmalignant conditions because of genetically affected other siblings within the family. Therefore, 75% to 90% of potential pediatric recipients require alternative allogeneic donor cells for treatment of their underlying conditions. Potential alternative allogeneic donor sources include unrelated cord blood donors, unrelated adult donors, and haploidentical family donors. In this article we review the experience of both unrelated cord blood donor and haploidentical family donor transplants in selected pediatric malignant and nonmalignant conditions.

  20. Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation

    International Nuclear Information System (INIS)

    Wang, Ya-Fei; Li, Qian; Xu, Wen-Gui; Xiao, Jian-Yu; Pang, Qing-Song; Yang, Qing; Zhang, Yi-Zuo

    2013-01-01

    Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia

  1. Romidepsin Used as Monotherapy in Sequence with Allogeneic Stem Cell Transplant in a Patient with Peripheral T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Nicholas Finn

    2014-01-01

    Full Text Available Despite advances in the field, a clear treatment algorithm for most peripheral T-cell lymphoma (PTCL subtypes remains to be defined. Generating reliable randomized data for this type of pathology remains a challenge because of the relative rarity of the disease and the heterogeneity of subtypes. Newer agents, such as the class-I selective histone deacetylase inhibitor romidepsin, have demonstrated efficacy and manageable toxicity in the relapsed and refractory setting. Whether novel agents should be used in conjunction with more conventional cytotoxic therapies or in sequence with a transplant strategy is unknown at this time. Here we report the successful use of romidepsin monotherapy as a bridge to allogeneic stem cell transplantation in a patient who had previously relapsed after several lines of conventional cytotoxic therapy for PTCL. Romidepsin provided the patient with sufficient disease control to proceed to transplantation while remaining in complete remission.

  2. Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants.

    Science.gov (United States)

    Goren Sahin, Deniz; Arat, Mutlu

    2017-12-01

    Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years' experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center. Two hundred and seven consecutive patients who underwent allogeneic peripheral blood stem cell transplantation were included in this study. Age, sex, weight, complete blood counts, CD34 + cell counts, total collected amount of CD34 + cells, CD34 + cells per 10l processed, mobilization failure and adverse events were reviewed. Median age was 40.2±12.9 (21-68) years and 46.4±13.4 (17-67) years for donors and patients, respectively. The number of donors who had undergone adequate CD34 + cell harvesting and completed the procedure on the fourth day was 67 (32.8% of all patients). Only 12 patients required cell apheresis both on day 5 and 6. Apheresis was completed on day 4 and/or day 5 in 94.2% of all our donors. There was no significant association between CD34 + stem cell volume and age, gender and weight values of donors. Mobilization failure was not seen in our series. G-CSF is highly effective in 1/3 of the donors on the 4th day in order to collect enough number of stem cells. We propose that peripheral stem cell collection might start on day 4th of G-CSF treatment for avoiding G-CSF related side effects and complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  4. Degree of Predicted Minor Histocompatibility Antigen Mismatch Correlates with Poorer Clinical Outcomes of Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation

    DEFF Research Database (Denmark)

    Larsen, Malene Erup; Kornblit, B; Larsen, Mette Voldby

    2010-01-01

    In fully HLA-matched allogeneic hematopoietic cell transplantations (HCT), the main mechanism of the beneficial graft-versus-tumor (GVT) effect and of the detrimental graft-versus-host disease (GVHD) is believed to be caused by donor cytotoxic T cells directed against disparate recipient minor hi...

  5. Biosimilar G-CSF based mobilization of peripheral blood hematopoietic stem cells for autologous and allogeneic stem cell transplantation.

    Science.gov (United States)

    Schmitt, Michael; Publicover, Amy; Orchard, Kim H; Görlach, Matthias; Wang, Lei; Schmitt, Anita; Mani, Jiju; Tsirigotis, Panagiotis; Kuriakose, Reeba; Nagler, Arnon

    2014-01-01

    The use of granulocyte colony stimulating factor (G-CSF) biosimilars for peripheral blood hematopoietic stem cell (PBSC) mobilization has stimulated an ongoing debate regarding their efficacy and safety. However, the use of biosimilar G-CSF was approved by the European Medicines Agency (EMA) for all the registered indications of the originator G-CSF (Neupogen (®) ) including mobilization of stem cells. Here, we performed a comprehensive review of published reports on the use of biosimilar G-CSF covering patients with hematological malignancies as well as healthy donors that underwent stem cell mobilization at multiple centers using site-specific non-randomized regimens with a biosimilar G-CSF in the autologous and allogeneic setting. A total of 904 patients mostly with hematological malignancies as well as healthy donors underwent successful autologous or allogeneic stem cell mobilization, respectively, using a biosimilar G-CSF (520 with Ratiograstim®/Tevagrastim, 384 with Zarzio®). The indication for stem cell mobilization in hematology patients included 326 patients with multiple myeloma, 273 with Non-Hodgkin's lymphoma (NHL), 79 with Hodgkin's lymphoma (HL), and other disease. 156 sibling or volunteer unrelated donors were mobilized using biosimilar G-CSF. Mobilization resulted in good mobilization of CD34+ stem cells with side effects similar to originator G-CSF. Post transplantation engraftment did not significantly differ from results previously documented with the originator G-CSF. The side effects experienced by the patients or donors mobilized by biosimilar G-CSF were minimal and were comparable to those of originator G-CSF. In summary, the efficacy of biosimilar G-CSFs in terms of PBSC yield as well as their toxicity profile are equivalent to historical data with the reference G-CSF.

  6. Dynamical System Modeling to Simulate Donor T Cell Response to Whole Exome Sequencing-Derived Recipient Peptides Demonstrates Different Alloreactivity Potential in HLA-Matched and -Mismatched Donor-Recipient Pairs.

    Science.gov (United States)

    Abdul Razzaq, Badar; Scalora, Allison; Koparde, Vishal N; Meier, Jeremy; Mahmood, Musa; Salman, Salman; Jameson-Lee, Max; Serrano, Myrna G; Sheth, Nihar; Voelkner, Mark; Kobulnicky, David J; Roberts, Catherine H; Ferreira-Gonzalez, Andrea; Manjili, Masoud H; Buck, Gregory A; Neale, Michael C; Toor, Amir A

    2016-05-01

    Immune reconstitution kinetics and subsequent clinical outcomes in HLA-matched recipients of allogeneic stem cell transplantation (SCT) are variable and difficult to predict. Considering SCT as a dynamical system may allow sequence differences across the exomes of the transplant donors and recipients to be used to simulate an alloreactive T cell response, which may allow better clinical outcome prediction. To accomplish this, whole exome sequencing was performed on 34 HLA-matched SCT donor-recipient pairs (DRPs) and the nucleotide sequence differences translated to peptides. The binding affinity of the peptides to the relevant HLA in each DRP was determined. The resulting array of peptide-HLA binding affinity values in each patient was considered as an operator modifying a hypothetical T cell repertoire vector, in which each T cell clone proliferates in accordance with the logistic equation of growth. Using an iterating system of matrices, each simulated T cell clone's growth was calculated with the steady-state population being proportional to the magnitude of the binding affinity of the driving HLA-peptide complex. Incorporating competition between T cell clones responding to different HLA-peptide complexes reproduces a number of features of clinically observed T cell clonal repertoire in the simulated repertoire, including sigmoidal growth kinetics of individual T cell clones and overall repertoire, Power Law clonal frequency distribution, increase in repertoire complexity over time with increasing clonal diversity, and alteration of clonal dominance when a different antigen array is encountered, such as in SCT. The simulated, alloreactive T cell repertoire was markedly different in HLA-matched DRPs. The patterns were differentiated by rate of growth and steady-state magnitude of the simulated T cell repertoire and demonstrate a possible correlation with survival. In conclusion, exome wide sequence differences in DRPs may allow simulation of donor alloreactive T

  7. Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations.

    Science.gov (United States)

    Matinlauri, Irma H; Kyllönen, Lauri E J; Salmela, Kaija T; Helin, Heikki; Pelzl, Steffen; Süsal, Caner

    2005-12-27

    In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (PsCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

  8. The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation.

    Science.gov (United States)

    Brifkani, Zaid; Brennan, Daniel C; Lentine, Krista L; Horwedel, Timothy A; Malone, Andrew F; Delos Santos, Rowena; Maw, Thin Thin; Alhamad, Tarek

    2017-03-01

    White recipients of 2-haplotype HLA-matched living kidney transplants are perceived to be of low immunologic risk. Little is known about the safety of induction avoidance and calcineurin inhibitor withdrawal in these patients. We reviewed our experience at a single center and compared it to Organ Procurement and Transplantation Network (OPTN) registry data and only included 2-haplotype HLA-matched white living kidney transplants recipients between 2000 and 2013. There were 56 recipients in a single center (where no induction was given) and 2976 recipients in the OPTN. Among the OPTN recipients, 1285 received no induction, 903 basiliximab, 608 thymoglobulin, and 180 alemtuzumab. First-year acute rejection rates were similar after induction-free transplantation among the center and induced groups nationally. Compared with induction-free transplantation in the national data, there was no decrease in graft failure risk over 13 years with use of basiliximab (adjusted hazard ratio [aHR], 0.86; confidence interval [CI], 0.68-1.08), Thymoglobulin (aHR, 0.92; CI, 0.7-1.21) or alemtuzumab (aHR, 1.18; CI, 0.72-1.93). Among induction-free recipients at the center, calcineurin inhibitor withdrawal at 1 year (n = 27) did not significantly impact graft failure risk (HR,1.62; CI, 0.38-6.89). This study may serve as a foundation for further studies to provide personalized, tailored, immunosuppression for this very low-risk population of kidney transplant patients.

  9. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    International Nuclear Information System (INIS)

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-01-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest

  10. The impact of center experience on results of reduced intensity:allogeneic hematopoietic SCT for AML. An analysis from the Acute Leukemia Working Party of the EBMT

    DEFF Research Database (Denmark)

    Giebel, S; Labopin, M; Mohty, M

    2013-01-01

    Allogeneic hematopoietic SCT with reduced-intensity conditioning (RIC-HSCT) is increasingly adopted for the treatment of older adults with AML. Our goal was to verify for the first time, if center experience influences outcome of RIC-HSCT. Results of 1413 transplantations from HLA-matched related...

  11. Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

    Directory of Open Access Journals (Sweden)

    Paolo Capozzi

    2014-09-01

    Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

  12. T Cell-Replete Peripheral Blood Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide Results in Outcomes Similar to Transplantation from Traditionally Matched Donors in Active Disease Acute Myeloid Leukemia.

    Science.gov (United States)

    How, Joan; Slade, Michael; Vu, Khoan; DiPersio, John F; Westervelt, Peter; Uy, Geoffrey L; Abboud, Camille N; Vij, Ravi; Schroeder, Mark A; Fehniger, Todd A; Romee, Rizwan

    2017-04-01

    Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT. We retrospectively analyzed data from 99 AML patients with active disease undergoing allogeneic HCT at a single institution. Forty-three patients received unrelated donor HCT, 32 patients received matched related donor HCT, and 24 patients received peripheral blood haploidentical HCT with post-transplantation cyclophosphamide. We found no significant differences between treatment groups in terms of overall survival (OS), event-free survival, transplantation-related mortality, cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GVHD). We performed univariate regression analysis of variables that modified OS in all patients and found only younger age at transplantation and development of chronic GVHD significantly improved outcome. Although limited by our relatively small sample size, these results indicate that haploidentical HCT in active AML patients have comparable outcomes to HCT with traditionally matched donors. Haploidentical HCT can be considered in this population of high-risk patients when matched donors are unavailable or when wait times for transplantation are unacceptably long. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  13. No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

    OpenAIRE

    Thiel, U.; Wawer, A.; Wolf, P.; Badoglio, M.; Santucci, A.; Klingebiel, T.; Basu, O.; Borkhardt, A.; Laws, H.-J; Kodera, Y.; Yoshimi, A.; Peters, C.; Ladenstein, R.; Pession, A.; Prete, A.

    2017-01-01

    Background: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia ...

  14. Long-term engraftment, graft-vs.-host disease, and immunologic reconstitution after experimental transplantation of allogeneic peripheral blood cells from G-CSF-treated donors.

    Science.gov (United States)

    Pan, L; Bressler, S; Cooke, K R; Krenger, W; Karandikar, M; Ferrara, J L

    1996-10-01

    Peripheral blood cells (PBPC) are an alternative source of bone marrow for allogeneic transplantation. Reports from recent clinical trials granulocyte colony-stimulating factor (G-CSF)-mobilized PBPC for allogeneic transplantation show incidence and severity of graft-vs.-host disease (GVHD) similar to those observed in conventional bone marrow transplantation (BMT), despite the presence of 10- to 20-fold more T cell in the PBPC inoculum. In the present study, we examined the effects of pretreatment of donors with G-CSF on GVHD, long-term engraftment, and lymphocyte reconstitution in a murine parent-->F1 model (B6.Ly-5a-->B6d2F1) using splenocytes as a source of peripheral progenitor cells. Recipients of splenocytes from G-CSF-treated donors experienced less mortality from acute GVHD and showed sustained weight gain by day 100 after transplantation. At that time, there was no histological evidence od GVHD in either liver or gut. Recipients of splenocytes from G-CSF-treated donors showed complete donor engraftment within 1 month, which was sustained until the end of the observation period. In contrast, recipients of T cell-depleted splenocytes showed slower donor engraftment and persistent donor/host chimerism. In addition, lymphocyte phenotype and function in mice receiving splenocytes from G-CSF-treated donors was significantly restored by day 100 after transplantation. Thus, the use of G-CSF-mobilized PBPC may provide significant advantages to conventional BMT by reducing GVHD without impairing long-term engraftment and immunologic reconstruction.

  15. Epstein-Barr virus (EBV) load in cerebrospinal fluid and peripheral blood of patients with EBV-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Liu, Q-F; Ling, Y-W; Fan, Z-P; Jiang, Q-L; Sun, J; Wu, X-L; Zhao, J; Wei, Q; Zhang, Y; Yu, G-P; Wu, M-Q; Feng, R

    2013-08-01

    To evaluate the diagnostic and prognostic utility of monitoring the Epstein-Barr virus (EBV) load in the cerebrospinal fluid (CSF) and peripheral blood for the patients with EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 172 patients undergoing allo-HSCT were enrolled in the study. The EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV-associated CNS diseases before the treatment and at different points following the treatment. Post-transplant EBV-associated diseases developed in 27 patients, including 12 patients with EBV-associated CNS diseases. The 3-year cumulative incidences of EBV-associated diseases and EBV-associated CNS diseases were 19.5 ± 3.5% and 8.6 ± 2.4%, respectively. Patients with EBV-associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA-emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3-14 days before the clinical manifestations of EBV-associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV-associated CNS diseases. In 12 patients with EBV-associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti-thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV-associated diseases and EBV-associated CNS diseases. EBV-associated CNS diseases are not rare after allo-HSCT. The EBV DNA loads of CSF could act as an important

  16. Homozygous HLA-C1 is Associated with Reduced Risk of Relapse after HLA-Matched Transplantation in Patients with Myeloid Leukemia.

    Science.gov (United States)

    Arima, Nobuyoshi; Kanda, Junya; Tanaka, Junji; Yabe, Toshio; Morishima, Yasuo; Kim, Sung-Won; Najima, Yuho; Ozawa, Yukiyasu; Eto, Tetsuya; Kanamori, Heiwa; Mori, Takehiko; Kobayashi, Naoki; Kondo, Tadakazu; Nakamae, Hirohisa; Uchida, Naoyuki; Inoue, Masami; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Kanda, Yoshinobu

    2018-04-01

    Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR], .79; P = .006) and chronic myelogenous leukemia (CML) (HR, .48; P = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR, .79, P = .069; unrelated: HR, .77, P = .022), preparative regimen (myeloablative: HR, .79, P = .014; reduced intensity: HR, .73, P = .084), and occurrence of acute graft-versus-host disease (yes: HR, .70, P = .122; no, HR .71, P = .026) or cytomegalovirus reactivation (reactivated: HR .67,P = .054; nonreactivated: HR .71, P = .033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR, .27; P < .001 and HR, .30; P = .002, respectively) and in children age <15 years (HR, .29; P < .001 and HR .31; P

  17. CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Jolanta B. Perz

    2012-01-01

    Full Text Available Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT largely relies on the graft-versus-leukemia (GVL effect. Uncontrolled graft-versus-host disease (GVHD is a feared complication of HSCT. Regulatory T cells (Treg are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD and chronic GVHD (cGVHD. Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.

  18. Remission induction using alemtuzumab can permit chemotherapy-refractory chronic lymphocytic leukemia (CLL) patients to undergo allogeneic stem cell transplantation.

    Science.gov (United States)

    Knauf, Wolfgang; Rieger, Kathrin; Blau, Wolfgang; Hegenbart, Ute; Von Gruenhagen, Ulrich; Niederwieser, Dietger; Thiel, Eckhard

    2004-12-01

    The outcome of allogeneic stem cell transplantation depends upon the disease status before transplantation. Patients with refractory disease are at high risk for relapse. To improve the curative potential of the transplant procedure, we treated 3 chemotherapy-refractory CLL patients with alemtuzumab before allogeneic stem cell transplantation. Prior to therapy, all patients suffered from B-symptoms, and had massive adenopathy, splenomegaly, thrombocytopenia, and anemia; two patients had hepatomegaly. Alemtuzumab greatly reduced tumor mass in blood and bone marrow, B-symptoms resolved, and organomegaly improved. Two patients became blood product independent. All patients proceeded to transplantation after conditioning with TBI 2 Gy (n=1) or Treosulfan (n=2) in combination with Fludarabine either from an HLA-matched sibling (n=2) or from an HLA-matched unrelated donor (n=1). All patients engrafted, and are alive and well. Two patients reached complete remission (CR); one patient attained stable partial remission (PR). These heavily pre-treated refractory patients gained substantial clinical benefit from alemtuzumab, and received successful allografts.

  19. Modulation of human allogeneic and syngeneic pluripotent stem cells and immunological implications for transplantation.

    Science.gov (United States)

    Sackett, S D; Brown, M E; Tremmel, D M; Ellis, T; Burlingham, W J; Odorico, J S

    2016-04-01

    Tissues derived from induced pluripotent stem cells (iPSCs) are a promising source of cells for building various regenerative medicine therapies; from simply transplanting cells to reseeding decellularized organs to reconstructing multicellular tissues. Although reprogramming strategies for producing iPSCs have improved, the clinical use of iPSCs is limited by the presence of unique human leukocyte antigen (HLA) genes, the main immunologic barrier to transplantation. In order to overcome the immunological hurdles associated with allogeneic tissues and organs, the generation of patient-histocompatible iPSCs (autologous or HLA-matched cells) provides an attractive platform for personalized medicine. However, concerns have been raised as to the fitness, safety and immunogenicity of iPSC derivatives because of variable differentiation potential of different lines and the identification of genetic and epigenetic aberrations that can occur during the reprogramming process. In addition, significant cost and regulatory barriers may deter commercialization of patient specific therapies in the short-term. Nonetheless, recent studies provide some evidence of immunological benefit for using autologous iPSCs. Yet, more studies are needed to evaluate the immunogenicity of various autologous and allogeneic human iPSC-derived cell types as well as test various methods to abrogate rejection. Here, we present perspectives of using allogeneic vs. autologous iPSCs for transplantation therapies and the advantages and disadvantages of each related to differentiation potential, immunogenicity, genetic stability and tumorigenicity. We also review the current literature on the immunogenicity of syngeneic iPSCs and discuss evidence that questions the feasibility of HLA-matched iPSC banks. Finally, we will discuss emerging methods of abrogating or reducing host immune responses to PSC derivatives. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

    1999-02-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  1. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    International Nuclear Information System (INIS)

    Yoshihara, Takao; Fujii, Noriko; Naya, Mayumi

    1999-01-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m 2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  2. Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

    Science.gov (United States)

    Ghosh, Nilanjan; Karmali, Reem; Rocha, Vanderson; Ahn, Kwang Woo; DiGilio, Alyssa; Hari, Parameswaran N.; Bachanova, Veronika; Bacher, Ulrike; Dahi, Parastoo; de Lima, Marcos; D’Souza, Anita; Fenske, Timothy S.; Ganguly, Siddhartha; Kharfan-Dabaja, Mohamed A.; Prestidge, Tim D.; Savani, Bipin N.; Smith, Sonali M.; Sureda, Anna M.; Waller, Edmund K.; Jaglowski, Samantha; Herrera, Alex F.; Armand, Philippe; Salit, Rachel B.; Wagner-Johnston, Nina D.; Fuchs, Ephraim; Bolaños-Meade, Javier

    2016-01-01

    Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD. PMID:27269951

  3. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

    Science.gov (United States)

    Eapen, Mary; Raetz, Elizabeth; Zhang, Mei-Jie; Muehlenbein, Catherine; Devidas, Meenakshi; Abshire, Thomas; Billett, Amy; Homans, Alan; Camitta, Bruce; Carroll, William L; Davies, Stella M

    2006-06-15

    The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.

  4. Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor

    DEFF Research Database (Denmark)

    Shamim, Z; Spellman, S; Haagenson, M

    2013-01-01

    Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes...... significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis...

  5. Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis.

    Science.gov (United States)

    Cutler, C; Giri, S; Jeyapalan, S; Paniagua, D; Viswanathan, A; Antin, J H

    2001-08-15

    Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.

  6. Allogenic lyophilized cartilage grafts for craniomaxillofacial reconstruction

    International Nuclear Information System (INIS)

    Pill Hoon Choung

    1999-01-01

    Allogenic lyophilized cartilages were made in our clinic after Sailer methods and some modification. In our clinic, we have used allogenic cartilage grafts on 102 defects of craniomaxillofacial area; 1) for defects from cyst or ameloblastoma, 2) for lack of continuity of the mandible, 3) for rhinoplasty, 4) for paranasal augmentation, 5) for augmentation genioplasty, 6) for reconstruction of orbital floor, 7) for oroantral fistula, 8) for temporal augmentation, 9) for TMJ surgery 10) for condyle defect as a costochondral graft, 11) for filling of tooth socket and alveolus augmentation,12) for correction or orbital height and 13) for guided bone regeneration in peripheral implant. The types of lyophilized cartilage used were chip, sheet and block types developed by freeze-dried methods. Some grafts showed change of ossification, in which case we could perform implant on it. We have good results on reconstruction of craniomaxillofacial defects. Allogenic cartilage have advantages such as 1) it has no immune reaction clinically, 2) it is more tolerable to infection than that of autogenous cartilage, 3) it has character of less resorption which require no over correction, 4) it is easy to manipulate contouring, and 5) it has possibility of undergoing ossification. Allogenic cartilage has been considered as good substitutes for bone. The author would like to report the results on 102 allogenic cartilage have

  7. Killer immunoglobulin-like receptor (KIR and HLA genotypes affect the outcome of allogeneic kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Izabela Nowak

    Full Text Available BACKGROUND: Recipient NK cells may detect the lack of recipient's (i.e., self HLA antigens on donor renal tissue by means of their killer cell immunoglobulin-like receptors (KIRs. KIR genes are differently distributed in individuals, possibly contributing to differences in response to allogeneic graft. METHODOLOGY/PRINCIPAL FINDINGS: We compared frequencies of 10 KIR genes by PCR-SSP in 93 kidney graft recipients rejecting allogeneic renal transplants with those in 190 recipients accepting grafts and 690 healthy control individuals. HLA matching results were drawn from medical records. We observed associations of both a full-length KIR2DS4 gene and its variant with 22-bp deletion with kidney graft rejection. This effect was modulated by the HLA-B,-DR matching, particularly in recipients who did not have glomerulonephritis but had both forms of KIR2DS4 gene. In contrast, in recipients with glomerulonephritis, HLA compatibility seemed to be much less important for graft rejection than the presence of KIR2DS4 gene. Simultaneous presence of both KIR2DS4 variants strongly increased the probability of rejection. Interestingly, KIR2DS5 seemed to protect the graft in the presence of KIR2DS4fl but in the absence of KIR2DS4del. CONCLUSIONS/SIGNIFICANCE: Our results suggest a protective role of KIR2DS5 in graft rejection and an association of KIR2DS4 with kidney rejection, particularly in recipients with glomerulonephritis.

  8. Allogeneic tumor cell vaccines

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies. PMID:24064957

  9. Kosten van allogene stamceltransplantaties

    NARCIS (Netherlands)

    M. van Agthoven (Michel); M.T. Groot (Martijn); C.A. Uyl-de Groot (Carin)

    2001-01-01

    textabstractAllogene stamceltransplantatie is een topspecialistische procedure die met succes kan worden ingezet in de behandeling van (hematologische) maligniteiten, met name bij leukemie. Van oudsher worden transplantaten van verwante donoren gebruikt, maar met de mogelijkheden om transplantaten

  10. Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans

    NARCIS (Netherlands)

    Choi, S.W.; Gatza, E.; Hou, G.; Sun, Y; Whitfield, J.; Song, Y.; Oravecz-Wilson, K.; Tawara, I.; Dinarello, C.A.; Reddy, P.

    2015-01-01

    We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant. Vorinostat treatment increased histone acetylation in peripheral blood mononuclear cells (PBMCs) from

  11. The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality.

    Science.gov (United States)

    Hill, Joshua A; Mayer, Bryan T; Xie, Hu; Leisenring, Wendy M; Huang, Meei-Li; Stevens-Ayers, Terry; Milano, Filippo; Delaney, Colleen; Sorror, Mohamed L; Sandmaier, Brenda M; Nichols, Garrett; Zerr, Danielle M; Jerome, Keith R; Schiffer, Joshua T; Boeckh, Michael

    2017-04-20

    Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007 to 2014. We used quantitative PCR to test for cytomegalovirus, BK polyomavirus, human herpesvirus 6B, HHV-6A, adenovirus, and Epstein-Barr virus between days 0 and 100 post-HCT. We evaluated risk factors for detection of multiple viruses and association of viruses with mortality through day 365 post-HCT with Cox models. Among 404 allogeneic HCT recipients, including 125 cord blood, 125 HLA-mismatched, and 154 HLA-matched HCTs, detection of multiple viruses was common through day 100: 90% had ≥1, 62% had ≥2, 28% had ≥3, and 5% had 4 or 5 viruses. Risk factors for detection of multiple viruses included cord blood or HLA-mismatched HCT, myeloablative conditioning, and acute graft-versus-host disease ( P values < .01). Absolute lymphocyte count of <200 cells/mm 3 was associated with greater virus exposure on the basis of the maximum cumulative viral load area under the curve (AUC) ( P = .054). The maximum cumulative viral load AUC was the best predictor of early (days 0-100) and late (days 101-365) overall mortality (adjusted hazard ratio [aHR] = 1.36, 95% confidence interval [CI] [1.25, 1.49], and aHR = 1.04, 95% CI [1.0, 1.08], respectively) after accounting for immune reconstitution and graft-versus-host disease. In conclusion, detection of multiple dsDNA viruses was frequent after allogeneic HCT and had a dose-dependent association with increased mortality. These data suggest opportunities to improve outcomes with better antiviral strategies. © 2017 by The American Society of Hematology.

  12. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

    2017-12-20

    Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

  13. Childhood Hematopoietic Cell Transplantation (PDQ®)—Health Professional Version

    Science.gov (United States)

    Hematopoietic cell transplantation involves the infusion of blood stem cells (peripheral/umbilical cord blood, bone marrow) into a patient to reconstitute the blood system. Get detailed information about autologous and allogeneic transplant, including cell selection, HLA matching, and preparative regimens, and the acute complications and late effects of treatment in this summary for clinicians.

  14. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

    Science.gov (United States)

    Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

    2017-11-14

    Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

  15. Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation.

    Science.gov (United States)

    Cantilena, Caroline R; Ito, Sawa; Tian, Xin; Jain, Prachi; Chinian, Fariba; Anandi, Prathima; Keyvanfar, Keyvan; Draper, Debbie; Koklanaris, Eleftheria; Hauffe, Sara; Superata, Jeanine; Stroncek, David; Muranski, Pawel; Barrett, A John; Battiwalla, Minoo

    2018-03-01

    Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios - FoxP3 + Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications. Published by Elsevier Inc.

  16. Peripheral neuropathy

    Science.gov (United States)

    ... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

  17. Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors.

    Science.gov (United States)

    Sivgin, Serdar; Karakus, Esen; Keklik, Muzaffer; Zararsiz, Gokmen; Solmaz, Musa; Kaynar, Leylagul; Eser, Bulent; Cetin, Mustafa; Unal, Ali

    2016-06-01

    In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy.

    Science.gov (United States)

    Messina, Chiara; Zecca, Marco; Fagioli, Franca; Rovelli, Attilio; Giardino, Stefano; Merli, Pietro; Porta, Fulvio; Aricò, Maurizio; Sieni, Elena; Basso, Giuseppe; Ripaldi, Mimmo; Favre, Claudio; Pillon, Marta; Marzollo, Antonio; Rabusin, Marco; Cesaro, Simone; Algeri, Mattia; Caniglia, Maurizio; Di Bartolomeo, Paolo; Ziino, Ottavio; Saglio, Francesco; Prete, Arcangelo; Locatelli, Franco

    2018-06-01

    We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34 + cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Differential diagnosis of skin lesions after allogeneic haematopoietic stem cell transplantation

    NARCIS (Netherlands)

    Canninga-van Dijk, MR; Sanders, CJ; Verdonck, LF; Fijnheer, R; van den Tweel, JG

    Allogeneic haematopoietic stem cell transplantation (i.e. bone marrow or peripheral blood stem cell transplantation) is a common procedure in the treatment of various haematological disorders such as aplastic anaemia, (pre)leukaemias, some malignant lymphomas, multiple myeloma and immunodeficiency

  20. Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT.

    Science.gov (United States)

    van Gelder, Michel; Ziagkos, Dimitris; de Wreede, Liesbeth; van Biezen, Anja; Dreger, Peter; Gramatzki, Martin; Stelljes, Matthias; Andersen, Niels Smedegaard; Schaap, Nicolaas; Vitek, Antonin; Beelen, Dietrich; Lindström, Vesa; Finke, Jürgen; Passweg, Jacob; Eder, Matthias; Machaczka, Maciej; Delgado, Julio; Krüger, William; Raida, Luděk; Socié, Gerard; Jindra, Pavel; Afanasyev, Boris; Wagner, Eva; Chalandon, Yves; Henseler, Anja; Schoenland, Stefan; Kröger, Nicolaus; Schetelig, Johannes

    2017-10-01

    Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted. Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%). Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Delayed allogeneic skin graft rejection in CD26-deficient mice.

    Science.gov (United States)

    Zhao, Xiangli; Zhang, Kai; Daniel, Peter; Wisbrun, Natali; Fuchs, Hendrik; Fan, Hua

    2018-03-23

    Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4 (DPPIV) in allogeneic skin graft rejection by tail-skin transplantation. Compared with wild-type (CD26 +/+ ) counterparts, CD26 -/- mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation. Concentrations of serum IgG, including its subclasses IgG1 and IgG2a, were significantly reduced in CD26 -/- mice during graft rejection. Moreover, after allogeneic skin transplantation, the secretion levels of the cytokines IFN-γ, IL-2, IL-6, IL-4, and IL-13 were significantly reduced, whereas the level of the cytokine IL-10 was increased in the serum of CD26 -/- mice compared with that in the serum of CD26 +/+ mice. Additionally, the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes (MPBLs) were both significantly lower, while the percentage of regulatory T cells (Tregs) was significantly higher in MPBLs of CD26 -/- mice than in those of CD26 +/+ mice. Furthermore, a lower percentage of CD8 + T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26 -/- mice were detected during graft rejection. These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells.

  2. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    International Nuclear Information System (INIS)

    Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

    1997-01-01

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  3. Transplante alogênico de células-tronco hematopoéticas em leucemias agudas: a experiência de dez anos do Hospital das Clínicas da UFMG Allogeneic hematopoietic stem cells transplantation in acute leukemia: ten years of experience in the Hospital das Clínicas - UFMG

    Directory of Open Access Journals (Sweden)

    Rosana M. Lamego

    2010-01-01

    Full Text Available As leucemias agudas são doenças com alta morbimortalidade para as quais o transplante alogênico de medula óssea é uma opção terapêutica eficaz. Neste artigo, relatamos a experiência de um centro brasileiro com pacientes apresentando leucemia aguda que receberam um enxerto de medula óssea ou células-tronco periféricas de um doador familiar HLA idêntico no período de julho de 1995 a dezembro de 2005. Foi realizado um estudo de coorte retrospectivo, analisando dados de 125 pacientes com mediana de idade de 28,7 anos. Oitenta e um pacientes (64,8% apresentavam leucemia mieloide aguda; 38 (30,4%, leucemia linfoide aguda; e seis (4,8%, leucemia bifenotípica. Trinta e dois pacientes encontravam-se em primeira remissão completa, 23 em segunda remissão e 70 com doença avançada (refratários, recidivados ou além da segunda remissão. A sobrevida global estimada em 10 anos foi de 22,9%. Em relação à situação clínica do paciente no momento do transplante, a sobrevida global em dez anos foi de 56,3% para pacientes em primeira remissão, 38% para os pacientes em segunda remissão, e 3,7% para os pacientes com doença avançada. Considerando-se os pacientes transplantados em primeira e segunda remissão, a evolução foi semelhante aos dados disponíveis na literatura. Entretanto, os resultados dos pacientes transplantados em fase avançada foram ruins, devendo-se discutir o papel do transplante para este grupo.Acute leukemias are a group of diseases with high morbimortality. Allogeneic bone marrow transplantation is an efficacious therapeutic option for their treatment. We report the experience of a Brazilian center in respect to acute leukemia patients who received a bone marrow or peripheral blood allograft from a HLA-matched sibling from July 1995 to December 2005. Data were retrospectively collected. The median age of the 125 patients included in the study was 28.7 years. Eighty-one patients presented with acute myeloid leukemia

  4. [Alternatives to allogenous blood transfusion].

    Science.gov (United States)

    Cernea, Daniela; Vlădoianu, Alice; Stoica, Maria; Novac, M; Berteanu, Cristina

    2009-01-01

    Blood transfusion is usually meant to lower morbidity and mortality rates. Allogenous blood transfusion implies certain risks that can be avoided by autologous blood transfusions techniques including: preoperatory autologous blood donation, acute normovolemic hemodilution, intraoperatory and postoperatory blood salvage. Preoperatory blood donation and acute normovolemic hemodilution are used for planned interventions with an estimated blood loss higher than 20% of blood volume. These methods imply Erythropoietin and iron treatment. Intraoperatory and postoperatory blood salvage is performed by personnel trained in blood donation, handling and storage. Autologous blood transfusions are used for certain surgical procedures that commonly require transfusions: orthopedic surgery, radical prostatectomy, cardiovascular surgery, organ transplantation. An alternative to allogenous blood transfusion is the use of artificial oxygen transporters: human or animal hemoglobin solutions or pefluorocarbonate solutions. These solutions do not require cross reactions, do not carry diseases and are generally well tolerated and easily stored in the operating room, ambulance and other transport means. They have however a slight degree of toxicity.

  5. Allogenic bone grafts in post-traumatic juxta-articular defects: Need for allogenic bone banking.

    Science.gov (United States)

    Mishra, Anil Kumar; Vikas, Rohit; Agrawal, H S

    2017-07-01

    Allogenic bone banking provide both structural and granular bone grafts for various orthopaedic, spinal, oncological and dental surgeries. However allogenic bones, presently, are not readily available. This article discusses the clinical applications of the allogenic grafts, the screening criteria and procedure for maintenance of such a bone banking facility. This article demonstrates the effective role of allogenic bone in a case of post-traumatic bone loss situation and discusses the growing need and present situation of bone banking in our country.

  6. Modulation of allogeneic stimulation in man. I. Characterization of an in vitro induced suppressor macrophage population

    International Nuclear Information System (INIS)

    Stux, S.V.; Dubey, D.P.; Yunis, E.J.

    1981-01-01

    Cultured human peripheral blood mononuclear cells suppressed the allogeneic response of fresh autologous lymphocytes. This suppressor activity developed gradually over a period of one week. The cells primarily responsible for this effect were enriched by Ficoll density gradient centrifugation. It was found that the suppressor cell is a large, low density nylon wool adherent, radioresistant, phagocytic, and nonspecific esterase positive mononuclear cell. Moreover, these cells did not form E rosettes and were Fc positive. Electron microscopy confirmed that suppressor cells were macrophage like. Suppressor activity was not due to cytotoxicity, crowding, or steric hinderance by the cultured cells. The suppressor macrophage population did not appear to inhibit the allogeneic response via prostaglandin or arginase release, or interfere with the tritiated thymidine uptake by release of endogenous thymidine. The above system is viewed as an in vitro model of immune regulation by suppressor macrophages, in the context of allogeneic response

  7. Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Hill, Brian T; Ahn, Kwang Woo; Hu, Zhen-Huan; Aljurf, Mahmoud; Beitinjaneh, Amer; Cahn, Jean-Yves; Cerny, Jan; Kharfan-Dabaja, Mohamed A; Ganguly, Siddhartha; Ghosh, Nilanjan; Grunwald, Michael R; Inamoto, Yoshihiro; Kindwall-Keller, Tamila; Nishihori, Taiga; Olsson, Richard F; Saad, Ayman; Seftel, Matthew; Seo, Sachiko; Szer, Jeffrey; Tallman, Martin; Ustun, Celalettin; Wiernik, Peter H; Maziarz, Richard T; Kalaycio, Matt; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Saber, Wael

    2018-03-01

    Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Kidney dysfunction after allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Kersting, S.

    2008-01-01

    Allogeneic stem cell transplantation (SCT) is a widely accepted approach for malignant and nonmalignant hematopoietic diseases. Unfortunately complications can occur because of the treatment, leading to treatment-related mortality. We studied kidney dysfunction after allogeneic SCT in 2 cohorts of

  9. Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor.

    Science.gov (United States)

    Shamim, Z; Spellman, S; Haagenson, M; Wang, T; Lee, S J; Ryder, L P; Müller, K

    2013-08-01

    Interleukin-7 (IL-7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α-chain of the IL-7R is polymorphic with the existence of SNPs that give rise to non-synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment-related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT. © 2013 John Wiley & Sons Ltd.

  10. BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

    Directory of Open Access Journals (Sweden)

    Young Hoon Park

    2016-08-01

    Full Text Available Objective: BK virus-hemorrhagic cystitis (BKV-HC is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT. We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and methods: From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: Hemorrhagic cystitis (HC was observed in 30 patients (43.5%, and among them, 18 patients (26.1% were identified as BKV-HC. The median age of the patients (12 males and 6 females was 45 years (range, 13-63. Patients received Allo-SCT from acute myeloid leukemia (n=11, aplastic anemia (n=4, myelodysplastic syndrome (n=2, and non-Hodgkin lymphoma (n=1.The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97 after transplantation and 22 days (range, 6-107. Eleven patients (62.1% had grade I-II HC and seven patients (38.9% had grade III-IV (high-grade HC. Among the seven patients who had high-grade HC, one had complete response (CR, one partial response (PR, and five no response (NR. Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2 and PR (n=2. The median duration from the start of leflunomide therapy to response was 13 days (range, 8–17 days. All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity. Materials

  11. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia

    Directory of Open Access Journals (Sweden)

    Simona Piemontese

    2017-01-01

    Full Text Available Abstract Background In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo versus matched (MUD 10/10 or mismatched unrelated donor at a single HLA-locus (MMUD 9/10 for patients with acute leukemia in remission. Methods Two hundred sixty-five adult patients with de novo acute leukemia in first or second remission that received a Haplo-SCT between January 2007 and December 2013 were compared with 2490 patients receiving a MUD 10/10 and 813 receiving a MMUD 9/10. Propensity score weighted analysis was conducted in order to control for disease risk imbalances between the groups. Results The weighted 3-year non-relapse mortality and relapse incidence were 29 and 30% for Haplo, 21 and 29% for MUD 10/10, and 29 and 25% for MMUD 9/10, respectively. The weighted 3-year leukemia-free survival (LFS and overall survival (OS were 41 and 46% for Haplo, 50 and 56% for MUD 10/10, and 46 and 48% for MMUD 9/10, respectively. Using weighted Cox model, both LFS and OS were significantly higher in transplants from MUD 10/10 compared from those in Haplo but not different between transplants from MMUD 9/10 and Haplo. The type of donor was not significantly associated with neither acute nor chronic graft-versus-host disease. Conclusions Patients with acute leukemia in remission have better outcomes if transplanted from a MUD 10/10. We did not find any significant difference in outcome between transplants from MMUD 9/10 and Haplo, suggesting that both can be equally used in the absence of a 10/10 MUD. Key point 1 Better outcomes using fully (10/10 matched unrelated donor for allo-SCT in acute leukemia in remission. Key point 2 Similar outcomes after allo

  12. Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

    Full Text Available Successful hematopoietic stem cell transplantation (HSCT, both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL and platelet (>20,000/µL reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT and 40 allogeneic bone marrow transplantation (BMT patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00 and 19.00 (16.00/23.00 and platelet on day 11.00 (10.00/13.00 and 21.00 (18.00/25.00, respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD and aplastic anemia (AA and MM presented the best overall survival (OS in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR, where CBV, melphalan (M-200 and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.

  13. The Role of Allogeneic Transplantation in the Treatment of Multiple Myeloma.

    Science.gov (United States)

    Majolino, I

    1998-01-01

    In multiple myeloma (MM) attempts to improve upon the results of standard melphalanpredisone with other conventional dose drug combinations, have generally been unsuccessful, producing only minor improvements in response rate, with little effect on survival. The only treatment capable of producing a dramatic change in response and life expectancy is high-dose chemo-radiotherapy followed by stem cell transplantation. However, after autologous transplant relapse will almost inevitably occur, and freedom from recurrence curves show no plateau in most studies. Besides the resistance of the disease to chemotherapy, another possible explanation is tumor contamination of the graft. This is one major advantage of allogeneic transplantation over autologous, the other being an immune mediated mechanism of tumor suppression in part related to GVHD. Application of allogeneic transplantation to MM has met a number of obstacles, but is now entering a phase of reappraisal, due in part to a tendency to earlier transplantation, in part to the use of novel technologies such as allogeneic peripheral blood stem cells instead of marrow. The goal should be the reduction of transplant related deaths, to better exploit the higher eradication potential of allogeneic cell therapies. The most intriguing perspectives are those related to immune manipulation of recipient and/or donor.

  14. Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

    Directory of Open Access Journals (Sweden)

    Itır Sirinoglu Demiriz

    2012-01-01

    Full Text Available The introduction of peripheral stem cell (PSC and cord blood (CB as an alternative to bone marrow (BM recently has caused important changes on hematopoietic stem cell transplantation (HSCT practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

  15. Total lymphoid irradiation (TLI) for allogeneic bone marrow transplantation in aplastic anemia

    International Nuclear Information System (INIS)

    Yamanashi, Syunji; Yamashita, Takashi; Mochizuki, Sachio; Hoshi, Masataka

    1985-01-01

    We used TLI as immunosuppression for BMT in a patient with aplastic anemia. He recieved high dose cyclophosphamide and single dose TLI with 750 cGy, 12 cGy/min at his midplane, and bone marrow from HLA-matched twin brother. He is surviving without complications at 15 months. This procedure is well tolerated regimen. (author)

  16. Graft-derived anti-HPA-2b production after allogeneic bone-marrow transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Jacobsen, N; Morling, N

    1994-01-01

    We report on a male who received a bone-marrow allograft from his HLA identical sister for acute myelogenous leukaemia. After transplantation, the patient suffered from refractoriness to the transfusions of HLA-matched platelets and a strong platelet-specific antibody, anti-HPA-2b, of IgG1 subcla...

  17. Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model.

    Science.gov (United States)

    Tsumanuma, Yuka; Iwata, Takanori; Kinoshita, Atsuhiro; Washio, Kaoru; Yoshida, Toshiyuki; Yamada, Azusa; Takagi, Ryo; Yamato, Masayuki; Okano, Teruo; Izumi, Yuichi

    2016-01-01

    Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of β-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest that

  18. Alternatives to allogeneic platelet transfusion.

    Science.gov (United States)

    Desborough, Michael J R; Smethurst, Peter A; Estcourt, Lise J; Stanworth, Simon J

    2016-11-01

    Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all. © 2016 John Wiley & Sons Ltd.

  19. Development of a coordinated allo T cell and auto B cell response against autosomal PTK2B after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Kremer, Anita N; van der Griendt, Judith C; van der Meijden, Edith D; Honders, M Willy; Ayoglu, Burcu; Schwenk, Jochen M; Nilsson, Peter; Falkenburg, J H Frederik; Griffioen, Marieke

    2014-02-01

    It is well known that allo-reactive T cells play a crucial role in graft-versus-leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct cytolysis, but may also stimulate production of IgG antibodies as helper cells. Immune complexes may subsequently be processed and presented by professional antigen presenting cells and stimulate induction of specific CD8(+) T cells. As such, proteins targeted in coordinated T- and B-cell responses may represent a class of immunodominant antigens in clinical responses after alloSCT. We previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid leukemia after HLA-matched alloSCT. Since PTK2B has also been described as antibody target, we here investigated whether a coordinated T- and B-cell response against PTK2B was induced. Patient serum before and after alloSCT and donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed observed development of a humoral immune response against PTK2B. Antibodies against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells, recognized a monomorphic region of the protein. To our knowledge, this is the first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive antibody response against an autosomal antigen.

  20. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

    Science.gov (United States)

    Ljungman, Per; Brand, Ronald; Hoek, Jennifer; de la Camara, Rafael; Cordonnier, Catherine; Einsele, Hermann; Styczynski, Jan; Ward, Katherine N; Cesaro, Simone

    2014-08-15

    The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial. A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database. Cox multivariate models were fitted to estimate the effect of donor CMV serological status on outcome. Seronegative patients receiving seropositive unrelated-donor grafts had decreased overall survival (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; P donors, whereas no difference was seen in patients receiving HLA-matched sibling grafts. Seropositive patients receiving grafts from seropositive unrelated donors had improved overall survival (HR, 0.92; 95% CI, .86-.98; P donors, if they had received myeloablative conditioning. This effect was absent when they received reduced-intensity conditioning. No effect was seen in patients grafted from HLA-identical sibling donors. The same association was found if the study was limited to patients receiving transplants from the year 2000 onward. We confirm the negative impact on overall survival if a CMV-seropositive unrelated donor is selected for a CMV-seronegative patient. For a CMV-seropositive patient, our data support selecting a CMV-seropositive donor if the patient receives a myeloablative conditioning regimen. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Peripheral reactions

    International Nuclear Information System (INIS)

    Greiner, D.

    1978-01-01

    Peripheral collisions, that is, collisions involving a small amount of overlap of nuclear matter, are discussed including inclusive interactions, the magnitude of the peripheral cross section, fragmentation, a compilation of experiments and available data, limiting fragmentation, factorization, some models, fragment momentum distributions, and future research directions

  2. Effect of radiotherapy on lymphocyte cytotoxicity against allogeneic lung cancer cells in patients with bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Toyohira, Ken; Yasumoto, Kosei; Manabe, Hideo; Ohta, Mitsuo; Terashima, Hiromi

    1979-01-01

    Cytotoxicity of peripheral blood lymphocytes against allogeneic target cells of bronchogenic carcinoma was examined by a microcytotoxicity test before, during, and after radiotherapy in primary lung cancer patients. Before the treatment, cytotoxicity was depressed only slightly in patients in stage III and strikingly in those in stage IV, as compared to the values in patients at earlier stages of lung cancer such as stages I and II. Local irradiation scarcely affected cytotoxicity at stages II and III, but augmented remarkably at stage IV. The number of peripheral blood lymphocytes decreased profoundly during and after radiotherapy in all cases of stages II, III, and IV. Although radiotherapy exhibited various effects on the cytotoxic activity of lymphocytes and the number of peripheral blood lymphocytes, only the cytotoxic activity at the end of radiotherapy correlated well with the reduction in tumor size. (author)

  3. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Luca Laurenti

    2010-08-01

    Full Text Available Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment. Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%: A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity. The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients. Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

  4. Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India

    Directory of Open Access Journals (Sweden)

    Rehan Khan

    2015-01-01

    Full Text Available Background & objectives: This study was aimed to report the occurrence of ocular graft versus host disease (oGVHD in allogeneic haematopoietic stem cell transplantation (allo-HSCT patients in a tertiary care hospital setting. Methods: A cross-sectional study of ocular surface of allo-HSCT patients was done. Slit lamp biomicroscopy, symptom score, tear meniscus height, fluorescein tear break-up time, Schirmer′s test I, ocular surface staining, dry eye severity, ocular surface disease index score were done. Indications for allo-HSCT, human leukocyte antigen (HLA matching, GVHD risk factor, systemic manifestation and treatment were also noted. Results: GVHD occurred in 44.4 per cent of 54 allo-HSCT patients (mean age 26.7 ± 12 yr included in the study. GVHD risk factors identified included female gender, relapse, older age of donor, cytomagelo virus (CMV reactivation, and multiparous female donors. oGVHD was noted in 31.5 per cent with mean time to occurrence being 17.8 ± 21.9 months after the allo-HSCT and was observed in 89.5 per cent of chronic GVHD cases. Acute GVHD (oral and dermatological involvement showed a significant association with GVHD in our patients (P< 0.001, 0R 23.0, CI 6.4-82.1. Chronic GVHD was observed to be associated with the occurrence of oGVHD (dry eye (P<0.001, OR = 24.0, CI 0.02 - 0.29. Of the 34 eyes with oGHVD, dry eye of level 3 severity was seen in 16, level 2 in six, level 1 in 12 eyes. Interpretation & conclusions: GVHD occurred in 44.4 per cent of the patients studied in the present study. Acute and chronic GVHD showed a strong association with oGVHD. Dry eye disease due to chronic oGVHD was observed in 17 (31.5% of 54 allo-HSCT patient with chronic oGVHD occurring in 17 (89.4% of chronic GVHD cases in allo-HSCT patients. Our study on oGVHD in post allo-HSCT patients in tertiary care centre points towards the fact that ocular morbidity due to dry eye disease as a result of oGVHD is a cause for concern in these

  5. Allogeneic radiation chimeras induced in SPF mice

    International Nuclear Information System (INIS)

    Sado, Toshihiko; Kamisaku, Hitoko

    1977-01-01

    During the past two decades much has been learned concerning the immunobiology of bone marrow chimeras induced in experimental animals as well as in man. However, from the basic as well as clinical points of view, there still remain many unsolved questions yet to be resolved. In this presentation, we discussed some of our recent results on the immunobiology of radiation chimeras induced in specific-pathogen-free (SPF) mice. These included the following: (a) contribution of graft versus host reaction (GVHR) as well non- GVHR mediated immunologic mechanism(s) to the expression of immunologic dysfunctions observed in allogeneic and certain semiallogeneic chimeras, (b) existence of immunoregulatory mechanism as a basis for the apparent lack of immunologic reactivity (tolerance) to the host- as well as to the donor-type alloantigens in situ in successful allogeneic bone marrow chimeras, and (c) the effect of microflora of the environment on the stability of such immunoregulatory mechanisms and its possible mechanism of action. (auth.)

  6. ALLOGENEIC TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Patrizia Chiusolo

    2010-05-01

    Full Text Available

    Even if Chronic lymphocytic leukemia (CLL often has an indolent behavior with good responsiveness to cytoreductive treatment, about 20% of the patients, so called "poor-risk" patients, show an aggressive course and die within a few years despite early intensive therapies. Criteria for poor-risk disease according to the European Bone Marrow Transplantation (EBMT CLL Transplant Consensus are: purine analogue refractoriness, early relapse after purine analogue combination therapy, CLL with p53 lesion requiring treatment.

    Allogeneic transplant has potential curative role in CLL, however burden with very  high transplant related mortality (TRM rates of 38-50%:

    A major advance in reducing the short-term morbidity and mortality of allogeneic stem cell transplantation (SCT has been the introduction of non-myeloablative or reduced intensity conditioning (RIC regimens to allow engraftment of allogeneic stem cells. There is no doubt that the crucial therapeutic principle of allo-SCT in CLL is graft versus leukemia (GVL activity.

    The major complications of allogeneic SCT in CLL are: chronic graft-versus-host-disease (GVHD affecting quality of life, high graft rejection and infection rates rates correlated with preexisting immunosuppression. Disease relapse remains the major cause of failure after RIC allo-HCT in CLL patients.

    Sensitive minimal residual disease (MRD quantification has strong prognostic impact after transplant.

     

  7. T cell reconstitution in allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Kielsen, K; Jordan, K K; Uhlving, H H

    2015-01-01

    Infections and acute graft-versus-host disease (aGVHD) are major causes of treatment-related mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). Both complications depend on reconstitution of the T-lymphocyte population based on donor T cells. Although...... it is well established that Interleukin-7 (IL-7) is a cytokine essential for de novo T cell development in the thymus and homoeostatic peripheral expansion of T cells, associations between circulating levels of IL-7 and T cell reconstitution following HSCT have not been investigated previously. We...... in patients treated with anti-thymocyte globulin (ATG) compared with those not treated with ATG (P = 0.0079). IL-7 levels at day +7 were negatively associated with T cell counts at day +30 to +60 (at day +60: CD3(+) : β = -10.6 × 10(6) cells/l, P = 0.0030; CD8(+) : β = -8.4 × 10(6) cells/l, P = 0.061; CD4...

  8. Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

    Science.gov (United States)

    Berman, Dora M.; Willman, Melissa A.; Han, Dongmei; Kleiner, Gary; Kenyon, Norman M.; Cabrera, Over; Karl, Julie A.; Wiseman, Roger W.; O'Connor, David H.; Bartholomew, Amelia M.; Kenyon, Norma S.

    2010-01-01

    OBJECTIVE To test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model of islet/bone marrow transplantation. RESEARCH DESIGN AND METHODS Cynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, and karyotype. Allogeneic donor MSCs were cotransplanted intraportally with islets on postoperative day (POD) 0 and intravenously with donor marrow on PODs 5 and 11. Recipients were followed for stabilization of blood glucose levels, reduction of exogenous insulin requirement (EIR), C-peptide levels, changes in peripheral blood T regulatory cells, and chimerism. Destabilization of glycemia and increases in EIR were used as signs of rejection; additional intravenous MSCs were administered to test the effect on reversal of rejection. RESULTS MSC phenotype and a normal karyotype were observed through passage 11. IL-6, IL-10, vascular endothelial growth factor, TGF-β, hepatocyte growth factor, and galectin-1 gene expression levels varied among donors. MSC treatment significantly enhanced islet engraftment and function at 1 month posttransplant (n = 8), as compared with animals that received islets without MSCs (n = 3). Additional infusions of donor or third-party MSCs resulted in reversal of rejection episodes and prolongation of islet function in two animals. Stable islet allograft function was associated with increased numbers of regulatory T-cells in peripheral blood. CONCLUSIONS MSCs may provide an important approach for enhancement of islet engraftment, thereby decreasing the numbers of islets needed to achieve insulin independence. Furthermore, MSCs may serve as a new, safe, and effective antirejection therapy. PMID:20622174

  9. GMP-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Okjae Lim

    Full Text Available Ex vivo-expanded, allogeneic natural killer (NK cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP conditions. After a single step of magnetic depletion of CD3(+ T cells, the depleted peripheral blood mononuclear cells (PBMCs were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(-CD16(+CD56(+ NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.

  10. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae; Chang, Jong Wook; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Kim, Jae-Sung; Jeon, Hong Bae

    2014-01-01

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications

  11. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Chang, Jong Wook [Research Institute for Future Medicine Stem Cell and Regenerative Medicine Center, Samsung Medical Center, Seoul 137-710 (Korea, Republic of); Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of); Kim, Jae-Sung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-709 (Korea, Republic of); Jeon, Hong Bae, E-mail: jhb@medi-post.co.kr [Biomedical Research Institute, MEDIPOST Co., Ltd, Seoul 137-874 (Korea, Republic of)

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  12. Clinical Benefit of Allogeneic Melanoma Cell Lysate-Pulsed Autologous Dendritic Cell Vaccine in MAGE-Positive Colorectal Cancer Patients

    DEFF Research Database (Denmark)

    Toh, Han Chong; Wang, Who-Whong; Chia, Whay Kuang

    2009-01-01

    PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs...... were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 x 10(6) cells per dose) at biweekly intervals. RESULTS: Twenty......-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding...

  13. Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT.

    Science.gov (United States)

    Giebel, Sebastian; Labopin, Myriam; Ibatici, Adalberto; Browne, Paul; Czerw, Tomasz; Socie, Gerard; Unal, Ali; Kyrcz-Krzemien, Slawomira; Bacigalupo, Andrea; Goker, Hakan; Potter, Mike; Furness, Caroline L; McQuaker, Grant; Beelen, Dietrich; Milpied, Noel; Campos, Antonio; Craddock, Charles; Nagler, Arnon; Mohty, Mohamad

    2016-03-01

    From a global perspective, the rates of allogeneic hematopoietic cell transplantation (alloHCT) are closely related to the economic status of a country. However, a potential association with outcome has not yet been documented. The goal of this study was to evaluate effects of health care expenditure (HCE), Human Development Index (HDI), team density, and center experience on nonrelapse mortality (NRM) after HLA-matched sibling alloHCT for adults with acute lymphoblastic leukemia (ALL). A total of 983 patients treated with myeloablative alloHCT between 2004 and 2008 in 24 European countries were included. In a univariate analysis, the probability of day 100 NRM was increased for countries with lower current HCE (8% vs. 3%; p = .06), countries with lower HDI (8% vs. 3%; p = .02), and centers with less experience (8% vs. 5%; p = .04). In addition, the overall NRM was increased for countries with lower current HCE (21% vs. 17%; p = .09) and HDI (21% vs. 16%; p = .03) and for centers with lower activity (21% vs. 16%; p = .07). In a multivariate analysis, the strongest predictive model for day 100 NRM included current HCE greater than the median (hazard ratio [HR], 0.39; p = .002). The overall NRM was mostly predicted by HDI greater than the median (HR, 0.65; p = .01). Both lower current HCE and HDI were associated with decreased probability of overall survival. Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. ©AlphaMed Press.

  14. Complications of allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Arnaout, Karim; Patel, Nihar; Jain, Maneesh; El-Amm, Joelle; Amro, Farah; Tabbara, Imad A

    2014-08-01

    Infection, graft-versus-host disease (GVHD), and to a lesser extent sinusoidal obstructive syndrome (SOS) represent the major causes of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). During the last decade, progress in prevention and treatment of these complications led to improvement in the outcome of these patients. Despite the fact that nonmyeloablative regimens have been increasingly used in elderly patients and in patients with co-morbidities, the nonrelapse related mortality remains a challenge and long-term follow-up is required. The objective of this manuscript is to provide an updated concise review of the complications of AHSCT and of the available treatment interventions.

  15. Antibody responses in allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Coico, R.F.

    1982-01-01

    The construction of long-lived allogeneic radiation chimeras, free of graft-versus-host disease, has been achieved using serologic elimination of Thy 1 + cells from donor bone marrow. Humoral immune function was not restored in these animals as evidenced by lack of primary antibody responses to a T cell-dependent antigen, namely, sheep erythrocytes (SRBC) both in vivo and in vitro. No evidence for a suppressor cell-mediated mechanism was found. Using separated chimera spleen cell populations and specific helper cell soluble mediators, the functional capabilities of chimera B cells, T cells, and macrophages were assessed. These findings suggested that the failure of chimeras to produce antibody is not the result of impaired B cell, T cell, or macrophage function, but rather, that it is due to ineffective cellular interactions. Physiologic cellular interactions depend upon the sharing of major histocompatibility complex (MHC) determinants between interacting cells. However, the self-recognition repertoire of developing T cells may be influenced by the environment which these cells differentiate such that they learn to recognize host MHC determinants as self. These findings support the interpretation that the immunologic hyporeactivity of allogeneic bone marrow chimeras reflects the role of the host environment in restricting the interactive capabilities of donor-derived cells

  16. Current issues in allogeneic islet transplantation.

    Science.gov (United States)

    Chang, Charles A; Lawrence, Michael C; Naziruddin, Bashoo

    2017-10-01

    Transplantation of allogenic pancreatic islets is a minimally invasive treatment option to control severe hypoglycemia and dependence on exogenous insulin among type 1 diabetes (T1D) patients. This overview summarizes the current issues and progress in islet transplantation outcomes and research. Several clinical trials from North America and other countries have documented the safety and efficacy of clinical islet transplantation for T1D patients with impaired hypoglycemia awareness. A recently completed phase 3 clinical trial allows centres in the United States to apply for a Food and Drug Administration Biologics License for the procedure. Introduction of anti-inflammatory drugs along with T-cell depleting induction therapy has significantly improved long-term function of transplanted islets. Research into islet biomarkers, immunosuppression, extrahepatic transplant sites and potential alternative beta cell sources is driving further progress. Allogeneic islet transplantation has vastly improved over the past two decades. Success in restoration of glycemic control and hypoglycemic awareness after islet transplantation has been further highlighted by clinical trials. However, lack of effective strategies to maintain long-term islet function and insufficient sources of donor tissue still impose limitations to the widespread use of islet transplantation. In the United States, wide adoption of this technology still awaits regulatory approval and, importantly, a financial mechanism to support the use of this technology.

  17. [A comparative study of unrelated donor and matched-sibling donor allogeneic hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia].

    Science.gov (United States)

    Zhou, J; Fu, Y W; Liang, L J; Wang, Q; Han, L J; Zu, Y L; Zhang, Yanli; Zhu, X H; Yu, F K; Fang, B J; Wei, X D; Song, Y P

    2016-12-01

    Objective: To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation(URD allo-HSCT) for children and adolescents with severe aplastic anemia (SAA). Methods: Clinical data of 34 SAA children and adolescents undergoing allo-HSCT were retrospectively analyzed from October 2001 to October 2015. According to the source of donor, the patients were divided into matched sibling donor allo-HSCT group (MSD group) and unrelated donor group (URD group). The clinical outcome of SAA children and adolescents receiving URD allo-HSCT was assessed, and patients in MSD allo-HSCT group were enrolled as control at the same period. Results: The rate of hematopoietic reconstitution, the time of neutrophil and platelet engraftment, incidence of chimerism and graft rejection between two groups were not statistically different.The incidence of acute graft-versus-host disease (GVHD) in URD group was significantly higher than that in MSD group [42.9%(6/14) vs 10.5%(2/19), P =0.047]. The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD in URD were higher than those in MSD group [21.4%(3/14) vs 5.3%(1/19), P =0.288; 35.7%(5/14) vs 5.3%(1/19), P =0.062, respectively], yet without significant difference between two groups. Other transplant-related complications including pulmonary complications, hemorrhagic cystitis, incidence of EBV and CMV reactivation and venous occlusive disease were comparable with two regimens. Estimated 5-years overall survival (OS) rate and disease free survival (DFS) rate were not statistically significant between URD group and MSD group [(84.4±6.6)% vs (89.4±7.1)%, (82.5±5.4)% vs (82.1±4.3)%; P =0.766, P =0.884, respectively]. Conclusions: By multivariate analysis, the outcome of URD allo-HSCT in SAA children and adolescent is similar to MSD allo-HSCT. It could be an alternative option as the first-line treatment for SAA children and adolescents without HLA matched sibling donors.

  18. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Baron, F; Labopin, M; Niederwieser, D

    2012-01-01

    This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

  19. Tissue-Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose-Derived Stromal Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Polina I. Bobyleva

    2016-01-01

    Full Text Available Human adipose tissue-stromal derived cells (ASCs are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA-stimulated peripheral blood mononuclear cells (PBMCs on ASCs under ambient (20% oxygen and “physiological” hypoxia (5% O2. As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle’ state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen-stimulated PBMCs. ASC/PBMCs interaction resulted in anti-inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue-related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under “physiological” hypoxia ASCs were less susceptible to “priming” by allogeneic mitogen-activated PBMCs.

  20. Allogeneic cellular immunotherapy for chronic B-cell leukemia

    NARCIS (Netherlands)

    Hoogendoorn, Mels

    2007-01-01

    Allogeneic stem cell transplantation (SCT) following reduced-intensity conditioning (RIC) as treatment modality has curative potential in patients suffering from chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL), illustrating susceptibility of these leukemic cells for the

  1. Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, N; Goedde-Salz, E; Loeffler, H [Christian-Albrechts-Univ., Kiel (Germany, F.R.)

    1985-06-01

    Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process.

  2. Specific allogeneic unresponsiveness in the adult host: present-day experimental models

    International Nuclear Information System (INIS)

    Rapaport, F.T.; Bachvaroff, R.J.; Cronkite, E.; Chanana, A.; Sato, T.; Asari, H.; Waltzer, W.C.

    1982-01-01

    As part of a long-term intensive effort to apply the induction of adult allogensic unresponsiveness to the transplantation problem, two techniques to control the variability in the persistence of immunologically competent postthymic cells iin the treated host and/or the inoculum of autologous marrow returned to the host after irradiation are described. The first consisted of exposing the peripheral blood of prospective recipients to a 5-week course of extra-corporeal irradiation (ECIB), the other of exposing the stored autologous marrow scheduled to repopulate a given recipient to methyl-prednisolone (MPd) and DNase prior to renifusion into the recipient. Serial analysis of bone marrow cell samples at various intervals before and after treatment was undertaken. The significance of the disappearance of a particular population of nonnuclear cells from the samples, and the association of such disappearance with increased success in the induction of allogeneic unresponsiveness is discussed

  3. Cytogenetic studies on recipients of allogeneic bone marrow transplants after fractionated total body irradiation

    International Nuclear Information System (INIS)

    Schmitz, N.; Goedde-Salz, E.; Loeffler, H.

    1985-01-01

    Cytogenetic findings from the bone marrow (BM) and the peripheral blood (PB) of nine consecutive patients after allogeneic bone marrow transplantation (BMT) for acute or chronic myelogenous leukaemia are reported. After a conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (TBI) given in five or six fractions of 2 Gy, persistence of host cells was detected in four out of seven cases with permanent engraftment. While one of these patients relapsed 4 months after host cells had been found in BM and PB, the other patients stayed relapse-free 124, 257 and 347 d after grafting. Before transplantation, the leukaemic cells in all three cases carried unique cytogenetic abnormalities giving the opportunity to distinguish the leukaemic population from chromosomally non-aberrant cells thought to represent residual normal host cells. As the persisting host cells after BMT lacked any cytogenetic abnormalities, it is suggested that they were members of residual normal clones not involved in the leukaemic process. (author)

  4. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo.

    Science.gov (United States)

    Pezzanite, Lynn M; Fortier, Lisa A; Antczak, Douglas F; Cassano, Jennifer M; Brosnahan, Margaret M; Miller, Donald; Schnabel, Lauren V

    2015-04-12

    This study tested the hypothesis that Major Histocompatibility Complex (MHC) incompatible equine mesenchymal stromal cells (MSCs) would induce cytotoxic antibodies to donor MHC antigens in recipient horses after intradermal injection. No studies to date have explored recipient antibody responses to allogeneic donor MSC transplantation in the horse. This information is critical because the horse is a valuable species for assessing the safety and efficacy of MSC treatment prior to human clinical application. Six MHC heterozygote horses were identified as non-ELA-A2 haplotype by microsatellite typing and used as allogeneic MHC-mismatched MSC recipients. MHC homozygote horses of known ELA-A2 haplotype were used as MSC and peripheral blood leukocyte (PBL) donors. One MHC homozygote horse of the ELA-A2 haplotype was the recipient of ELA-A2 donor MSCs as an MHC-matched control. Donor MSCs, which were previously isolated and immunophenotyped, were thawed and culture expanded to achieve between 30x10(6) and 50x10(6) cells for intradermal injection into the recipient's neck. Recipient serum was collected and tested for the presence of anti-donor antibodies prior to MSC injection and every 7 days after MSC injection for the duration of the 8-week study using the standard two-stage lymphocyte microcytotoxicity dye-exclusion test. In addition to anti-ELA-A2 antibodies, recipient serum was examined for the presence of cross-reactive antibodies including anti-ELA-A3 and anti-RBC antibodies. All MHC-mismatched recipient horses produced anti-ELA-A2 antibodies following injection of ELA-A2 MSCs and developed a wheal at the injection site that persisted for the duration of the experiment. Anti-ELA-A2 antibody responses were varied both in terms of strength and timing. Four recipient horses had high-titered anti-ELA-A2 antibody responses resulting in greater than 80% donor PBL death in the microcytotoxicity assays and one of these horses also developed antibodies that cross

  5. Biodistribution and Immunogenicity of Allogeneic Mesenchymal Stem Cells in a Rat Model of Intraarticular Chondrocyte Xenotransplantation

    Directory of Open Access Journals (Sweden)

    Maribel Marquina

    2017-11-01

    response. IL-2 measurements in cocultures of rat peripheral blood lymphocytes with PAC indicated that PAC injection induced some T-cell hyporesponsiveness that was not enhanced in the cohorts additionally receiving MSC. Thus, PAC injected intraarticularly in Lewis rats induced a cellular and humoral immune response that was not counteracted by the systemic administration of allogeneic MSC under the described conditions.

  6. Present and future of allogeneic natural killer cell therapy

    Directory of Open Access Journals (Sweden)

    Okjae eLim

    2015-06-01

    Full Text Available Natural killer (NK cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA-haploidentical hematopoietic stem cell transplantation revealed the anti-tumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor (KIR ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions.

  7. Tenogenically induced allogeneic mesenchymal stem cells for the treatment of proximal suspensory ligament desmitis in a horse

    Directory of Open Access Journals (Sweden)

    Aurelie eVandenberghe

    2015-10-01

    Full Text Available Suspensory ligament injuries are a common injury in sport horses, especially in competing dressage horses. Because of the poor healing of chronic recalcitrant tendon injuries, this represents a major problem in the rehabilitation of sport horses and often compromises the return to the initial performance level. Stem cells are considered as a novel treatment for different pathologies in horses and humans. Autologous mesenchymal stem cells (MSCs are well known for their use in the treatment of tendinopathies, however, recent studies report a safe use of allogeneic MSCs for different orthopaedic applications in horses. Moreover, it has been reported that predifferentiation of MSCs prior to injection might result in improved clinical outcomes. For all these reasons, the present case report describes the use of allogeneic tenogenically induced peripheral blood-derived MSCs for the treatment of a proximal suspensory ligament injury. During conservative management for 4 months, the horse demonstrated no improvement of a right front lameness with a Grade 2/5 on the AAEP scale and a clear hypo-echoic area detectable in 30% of the cross sectional area. From 4 weeks after treatment, the lameness reduced to an AAEP Grade 1/5 and a clear filling of the lesion could be noticed on ultrasound. At 12 weeks (T4 after the first injection, a second intralesional injection with allogeneic tenogenically induced MSCs and PRP was given and at 4 weeks after the second injection (T5, the horse trotted sound under all circumstances with a close to total fiber alignment. The horse went back to previous performance level at 32 weeks after the first regenerative therapy and is currently still doing so (i.e. 20 weeks later or 1 year after the first stem cell treatment.In conclusion, the present case report demonstrated a positive evolution of proximal suspensory ligament desmitis after treatment with allogeneic tenogenically induced MSCs.

  8. Plerixafor (a CXCR4 antagonist following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery

    Directory of Open Access Journals (Sweden)

    Michael M. B. Green

    2016-08-01

    Full Text Available Abstract Background The binding of CXCR4 with its ligand (stromal-derived factor-1 maintains hematopoietic stem/progenitor cells (HSPCs in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT promotes hematopoiesis by inducing HSC proliferation. Methods We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis. Results Thirty patients received plerixafor following peripheral blood stem cell (n = 28 (PBSC or bone marrow (n = 2 transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04 and platelet recovery >20 K (p = 0.04 compared to the controls. Conclusions Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted. Trial registration ClinicalTrials.gov NCT01280955

  9. Immune transfer studies in canine allogeneic marrow graft donor-recipient pairs

    International Nuclear Information System (INIS)

    Grosse-Wilde, H.; Krumbacher, K.; Schuening, F.D.; Doxiadis, I.; Mahmoud, H.K.; Emde, C.; Schmidt-Weinmar, A.; Schaefer, U.W.

    1986-01-01

    Transfer of immunity occurring with bone marrow grafting was studied using the dog as a preclinical model. Allogeneic bone marrow transplantation (BMT) was performed between DLA-identical beagle litter-mates. The donors were immunized with tetanus toxoid (TT) or sheep red blood cells (SRBC), and their humoral response was monitored by hemagglutination. The recipients of bone marrow from TT-immunized donors showed a marked increase of antibody titer one week posttransplantation, while in the recipients of marrow from SRBC immunized donors the antibody titers were considerably lower. Within the following 60 days the antibody titers in both groups diminished gradually to pregrafting levels. Control experiments in which cell-free plasma from donors immunized with TT and SRBC respectively was transfused indicated that the initial rise of specific antibody titers after marrow grafting is likely to be due to a passive transfer of humoral immunity. A single challenge of these marrow graft recipients with the respective antigen 15-18 weeks posttransplantation led to a secondary type of humoral immune response. It could be demonstrated that transfer of memory against TT or SRBC was independent from the actual antibody titer and the time of vaccination of the donor. One dog was immunized with TT after serving as marrow donor. When the donor had shown an antibody response, a peripheral blood leukocytes (PBL) transfusion was given to his chimera. Subsequent challenge of the latter resulted in a secondary type of specific antibody response. This indicates that specific cellular-bound immunological memory can be transferred after BMT from the donor to his allogeneic bone marrow chimera by transfusion of peripheral blood leukocytes. The data may be of importance in clinical BMT to protect patients during the phase of reduced immune reactivity by transfer of memory cells

  10. Ocular findings after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tabbara, Khalid F; Al-Ghamdi, Ahmad; Al-Mohareb, Fahad; Ayas, Mouhab; Chaudhri, Naeem; Al-Sharif, Fahad; Al-Zahrani, Hazzaa; Mohammed, Said Y; Nassar, Amr; Aljurf, Mahmoud

    2009-09-01

    To study the incidence, causes, and outcome of major ocular complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective, noncomparative, observational clinical study. The study included a total of 620 patients who underwent allogeneic HSCT in the period from 1997 to 2007 at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. Allogeneic HSCT. Patients with ocular complications were referred to the ophthalmology division for complete ophthalmologic examination, including visual acuity, tonometry, Schirmer test, biomicroscopy, and dilated ophthalmoscopy. Laboratory investigations were performed whenever indicated. The incidence and causes of major ocular complications after allogeneic HSCT were determined. Visual acuity at 1 year after allogeneic HSCT was recorded. Major ocular complications occurred in 80 (13%) of 620 patients who underwent allogeneic HSCT. There were 36 male patients (45%) and 44 female patients (55%) with a mean age of 29 years and an age range of 9 to 65 years. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate in 69 patients, and cyclosporine, methotrexate and corticosteroids, or mycophenolate mofetil in 11 patients. The most frequently encountered ocular complications were chronic GVHD, dry eye syndrome without GVHD, corneal ulcers, cataract, glaucoma, cytomegalovirus retinitis, fungal endophthalmitis, and acquisition of allergic conjunctivitis from atopic donors. There was no correlation between the pattern of ocular complications and the transplanted stem cell source. Best-corrected visual acuity (BCVA) at 1 year after transplantation was less than 20/200 in 13 patients (16%), less than 20/50 in 17 patients (21%), and better than 20/50 in 50 patients (63%). Ocular complications are common in patients undergoing allogeneic HSCT. Early recognition and prompt treatment are important. The author(s) have no proprietary or commercial

  11. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

    1982-01-01

    A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

  12. HLA matching and the United Network for Organ Sharing Allocation System: impact of HLA matching on African-American recipients of cadaveric kidney transplants.

    Science.gov (United States)

    Rebellato, Lorita M; Arnold, Angelo N; Bozik, Karen M; Haisch, Carl E

    2002-12-15

    A recent proposal supports the elimination of allocation points for human leukocyte antigen (HLA) mismatches (MM) in cadaveric kidney transplantation. The intent is to increase access for some racial groups that might be disadvantaged by the representation of race-specific HLA in a largely white donor pool. We report our experience from two transplant centers that serve a large African American (AA) patient population. All cadaveric transplants into AA recipients from 1994 to 2000 (n=162) were included in a retrospective review. Superior graft survival was observed in AA recipients of 0 MM transplants. When induction therapy was used, the graft survival at 3 years for the human leukocyte antigen (HLA)-BDR MM grades given allocation points (0,1,2 MM) was 82% versus only 49% for BDR MM grades not given points (3,4 MM: =0.0022). Our collective experience demonstrates that AA patients having HLA-BDR MM grades given allocation points had better graft survival. Removing points for HLA from the national allocation system may result in significantly poorer outcome in AA kidney recipients.

  13. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery

    NARCIS (Netherlands)

    van der Linden, P.; de Hert, S.; Daper, A.; Trenchant, A.; Jacobs, D.; de Boelpaepe, C.; Kimbimbi, P.; Defrance, P.; Simoens, G.

    2001-01-01

    PURPOSE: Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. METHODS: This prospective

  14. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    International Nuclear Information System (INIS)

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-01-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI

  15. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report

    Directory of Open Access Journals (Sweden)

    Behre Gerhard

    2009-03-01

    Full Text Available Abstract Introduction We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. Case presentation A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. Conclusion As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  16. Successful treatment of severe sinusoidal obstruction syndrome despite multiple organ failure with defibrotide after allogeneic stem cell transplantation: a case report.

    Science.gov (United States)

    Behre, Gerhard; Theurich, Sebastian; Christopeit, Maximilian; Weber, Thomas

    2009-03-10

    We report a case of sinusoidal obstruction syndrome, a typical and life-threatening complication after allogeneic stem-cell transplantation, successfully treated with defibrotide despite massive multiple organ failure. A 64-year-old Caucasian woman underwent allogeneic peripheral blood stem-cell transplantation from her human leukocyte antigen-identical sister against aggressive lymphoplasmocytoid immunocytoma. Seven days later, the patient developed severe sinusoidal obstruction syndrome according to the modified Seattle criteria. We initiated treatment with defibrotide. Despite early treatment, multiple organ failure with kidney failure requiring dialysis and ventilator-dependent lung failure aggravated the clinical course. Furthermore, central nervous dysfunction occurred as well as transfusion refractory thrombocytopenia. As highlighted in our report, defibrotide is the most promising drug in the treatment of the formerly, almost lethal, severe sinusoidal obstruction syndrome to date. This is demonstrated very clearly in our patient. She improved completely, even after renal, cerebral and respiratory failure.

  17. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    Science.gov (United States)

    Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Bacterial infections associated with allogenic bone transplantation

    Directory of Open Access Journals (Sweden)

    Stepanović Željko Lj.

    2015-01-01

    Full Text Available Background/Aim. Bone allografts are frequently used in orthopedic reconstructive procedures carrying a high risk for recipients. To assess the nature and frequency of allograft contamination and associated surgical infection the case records from our institutional bone bank were reviewed. Methods. We retrospectively analyzed the microbiology of discarded bone allografts and the surgical site of the recipients. A case series of patients who acquired surgical site infection after allogenic bone transplantation was presented. Swab culturing was conducted on 309 femoral heads from living donors who underwent partial and total hip arthroplasty between January 2007 and December 2013. To prevent potential bone allograft contamination we used saline solution of 2.0 mg/ml of amikacin during thawing. The overall infection rate was analyzed in 197 recipients. Results. Of the 309 donated femoral heads, 37 were discarded due to bacterial contamination, giving the overall contamination rate of 11.97%. The postoperative survey of 213 bone allotransplantations among 197 recipients showed the infection rate of 2.03%. The coagulase-negative Staphylococcus was the most commonly identified contaminant of bone allografts and recipient surgical sites. Conclusion. The allograft contamination rate and the infection rate among recipients in our institution are in accordance with the international standards. The coagulase-negative Staphylococcus was the most commonly identified contaminant of bone allografts and recipient surgical sites. There is no strong evidence that surgical site infections were associated with bone allograft utilization. We plan further improvements in allograft handling and decontamination with highly concentrated antibiotic solutions in order to reduce infection risk for recipients.

  19. Acquisition and Cure of Autoimmune Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Hsin-An Hou

    2007-09-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia who received bone marrow transplantation from her human leukocyte antigen (HLA-identical sister who had a history of Graves' disease. Antithyroid antibodies, including antimicrosomal antibody and antithy-roglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjögren's syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkin's lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjögren's syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjögren's syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.

  20. Endothelial and circulating progenitor cells in hematological diseases and allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Ruggeri, Annalisa; Paviglianiti, Annalisa; Volt, Fernanda; Kenzey, Chantal; Rafii, Hanadi; Rocha, Vanderson; Gluckman, Eliane

    2017-10-12

    Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells which are not associated with vessel walls, and that are detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and some other diseases. Consequently, CECs and EPCs represent a potential biomarker in several clinical conditions involving endothelial turnover and remodeling, such as hematological diseases. These cells may be involved in disease progression and the neoplastic angiogenesis process. Moreover, CESs and EPCs are probably involved in endothelial damage that is a marker of several complications following allogeneic hematopoietic stem cell transplantation. This review aims to provide an overview on the characterization of CECs and EPCs, describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Ready-made allogeneic ABO-specific serum eye drops

    DEFF Research Database (Denmark)

    Harritshøj, Lene Holm; Nielsen, Connie; Ullum, Henrik

    2014-01-01

    serum treatment. CONCLUSION: Ready-made ABO-identical allogeneic serum eye drops were straightforwardly produced, quality-assured and registered as a safe standard blood product for the treatment of certain cases of severe dry eye disease. Therapeutic efficacy was comparable to previous reports......PURPOSE: To overcome problems and delays of the preparation of autologous serum eye drops, a production line of ABO-specific allogeneic serum eye drops from male blood donors was set up in a blood bank. Feasibility, clinical routine, safety and efficacy were evaluated in a cohort of patients...

  2. Propylthiouracil and peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Valentina Van Boekel

    1992-06-01

    Full Text Available Peripheral neuropathy is a rare manifestation in hyperthyroidism. We describe the neurological manifestations of a 38 year old female with Graves' disease who developed peripheral neuropathy in the course of her treatment with propylthiouracil. After the drug was tapered off, the neurological signs disappeared. Therefore, we call attention for a possible toxic effect on peripheral nervous system caused by this drug.

  3. Lyophilized allogeneic bone grafts for cystic and discontinuity defects of the jaws

    International Nuclear Information System (INIS)

    Pill Hoon Choung; Eun Seok Kim

    1999-01-01

    Allogenic bone grafts have been used after various processing in each institute was made by lyophilized allogenic bone and used for maxillofacial reconstruction. Three types of lyophilized allogenic bone grafts as powder, chip and block form were performed to reconstruct the following defects: 1) maxillectomy, 2) mandiblectomy, 3) cystectomy, 4) cleft alveolus, 5) gap in orthognathic osteotomy, 6) peri-implant defect, 7) extraction socket, and 8) facial contouring. Above defects can be classified as cystic and discontinuity defects of the maxilia and the mandible. Because discontinuity defects have more difficult problems to reconstruct considering mechanical strength of the allogenic bone. We performed allogenic bone grafts on 50 cystic defects and 12 discontinuity defects of the jaws. Among them, 3 cases were removed due to infection, and the others had no complications. In reconstruction of cystic defects, the defects were filled with allogenic chip which were made from allogenic block bone at the surgery, which later were changed to host bone. Three cases of them showed tooth eruption through the allogenic bone grafting site, changing the eruption pathway, which was interrupted by the lesion. in reconstruction of discontinuity defects, usually allogenic bone has been used as a tray, in which PMCB or demineralized bone chips were filled. But we tried to reconstruct this discontinuity defect using allogeneic bone block without inside filling of PMCB different from tray type. We will present the results of allogenic bone grafts using cranial bone, costochondral graft, and the mandible

  4. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K. H.; Schjødt, I.; Syrjala, K. L.

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  5. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    the course of allogeneic stem cell transplantation (SCT). Twenty SCT patients were included in the study. suPAR was measured by ELISA in daily taken plasma samples during the pretransplant conditioning with chemotherapy and weekly for 1 month after infusion of the graft. suPAR levels before the start...

  6. Single-centre experience of allogeneic haemopoietic stem cell ...

    African Journals Online (AJOL)

    Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is used to treat a broad but well-defined range of paediatric conditions, most frequently in paediatric oncology for treatment intensification or salvage therapy for acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL). Allo-HSCT is also indicated in.

  7. Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

    Directory of Open Access Journals (Sweden)

    Eolia Brissot

    2017-06-01

    Full Text Available Abstract Background Primary refractory acute myeloid leukemia (PRF-AML is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. Methods The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660 versus unrelated donors (n = 381, for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS. Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. Conclusions HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an

  8. Tolerance, immunocompetence, and secondary disease in fully allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Rayfield, L.S.; Brent, L.

    1983-01-01

    The aim of this study was to ascertain the extent to which secondary disease and mortality in fully allogeneic chimeras (C57BL leads to CBA) is caused (if at all) by a delayed graft-versus-host reaction. Adult CBA males were thymectomized, irradiated, and reconstituted with T-lymphocyte-depleted C57BL or CBA bone marrow cells (BMC), followed three weeks after irradiation by implantation under the kidney capsule of thymic lobes from C57BL or CBA fetal or adult donors. These mice were observed for the development of secondary disease for periods in excess of 250 days, and they were examined at 5 weeks or 4 months for T lymphocyte reactivity and tolerance to alloantigens, using the cell-mediated lympholysis assay (CML). The following results were obtained. First, removal of T lymphocytes with anti-Thy 1 antibody and complement from allogeneic bone marrow did not prevent wasting and eventual death, although it prolonged the lifespan of mice substantially. Second, T lymphocytes generated from bone marrow-derived precursor cells became tolerant of the histocompatibility antigens of the thymus donor strain but remained normally reactive to third-party antigens. Third, allogeneic radiation chimeras did not survive as well as animals reconstituted with syngeneic cells, even when they were demonstrably tolerant in CML. Fourth, C57BL BMC maturing in a CBA host equipped with a C57BL thymus graft did not become tolerant of host antigens, indicating that extra-thymic tolerance does not occur in fully allogeneic--as opposed to semiallogeneic--chimeras. It is argued that the function of B lymphocytes and/or accessory cells is impaired in fully allogeneic radiation chimeras, and that the mortality observed was directly related to the resulting immunodeficiency. The relevance of the results described in this paper to clinical bone marrow transplantation is discussed

  9. 'Mini' total body irradiation and allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gocheva, L.; Sergieva, K.; Koleva, I.; Avramova, V.; Vassileva, V.; Georgieva, S.; Sultanov, B.

    2006-01-01

    Full text: The total body irradiation (TBI) combined with intensive chemotherapy plays an important role in the preparation of patients for bone marrow transplantation (BMT). The first autologous BMT in Bulgaria was performed in 1997 in the Specialized Pediatric Hospital for Active Treatment (SPHAT) of oncohematological diseases. The first TBI, followed by allogeneic BMT, was carried out in 2002 in the 'Queen Giovanna' University Hospital, after which its routine application as a basic form of large field radiotherapy and a main stage of the conditioning regimen for BMT was started. Fourteen allogeneic BMTs including TBI as a basic conditioning regimen have been performed till May 2006. The objective of the present report is to present the first clinical observations in the Bulgarian oncological practice on 'mini' TBI followed by allogeneic blood stem cell transplantation. During the period October 2005 - May 2006, 'mini' TBI followed by allogeneic BMT was carried out for two patients of the age 43 and 50 years. The diagnosis of both patients was acute non-lymphoblastic leukemia, in the remission stage, after one relapse, respectively. Intensive preceding chemotherapy was applied for both patients. A conditioning regimen was applied including the fludarabine purine analogue (3 x 30 mg/m 2 ) and 200 cGy TBI. It was followed by transplantation of allogeneic cell concentrate containing 2.5 x10 6 /kg CD34+ and 4.0 x10 6 /kg CD34+ blood stem cells of partially compatible family donors (a sister and a son), which were tolerable for the patients without complications. Cyclosporine and mycophelonate mofetile were applied as post-transplantation treatment. Active antibiotic, antiviral, symptomatic and substituting therapy, as well as GvHD prophylaxis was applied for both patients. Good clinical tolerance was recorded for the applied low dose conditioning regimen. The patients were discharged within 30 days in good general condition and stable draft action, with

  10. Peripheral Neuropathy and Agent Orange

    Science.gov (United States)

    ... Enter ZIP code here Enter ZIP code here Peripheral Neuropathy and Agent Orange VA presumes Veterans' early-onset ... 10 percent disabling by VA's rating regulations. About peripheral neuropathy Peripheral neuropathy is a condition of the peripheral ...

  11. Allogeneic hematopoietic cell transplantation (allogeneic HCT) for treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Burke, Michael J; Cao, Qing; Trotz, Barb; Weigel, Brenda; Kumar, Ashish; Smith, Angela; Verneris, Michael R

    2009-12-15

    Allogeneic hematopoietic cell transplant (HCT) with best available donor for children with Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL) has previously been considered standard practice. Since the introduction of imatinib into the treatment of this disease, the role of allogeneic HCT is more uncertain. We investigated the impact of remission status, graft source, and imatinib use on transplant outcomes for 37 children with Ph+ ALL who received an allogeneic HCT at the University of Minnesota between 1990 and 2006. The median age at HCT was 7.47 (range; 1.4-16.4) years. Thirteen patients received imatinib therapy pre- and/or post-HCT (imatinib group) and 24 patients, received either no imatinib (n = 23) or only post-HCT relapse (n = 1) (non-imatinib group). There was no difference in disease-free survival (DFS) or relapse between the imatinib and non-imatinib groups at 3 years (62%/15% vs. 53%/26%; P = 0.99; 0.81, respectively). There was no significant difference in transplant outcomes between matched related donor or unrelated donor (umbilical cord blood or matched unrelated marrow) recipients whereas patients receiving allogeneic HCT in first remission (CR1) had superior DFS and less relapse compared to patients transplanted in >or=CR2 (71%/16% vs. 29%/36%; P = 0.01; P = 0.05). Based on this retrospective analysis at a single institution, the use of imatinib either pre- and/or post-transplant does not appear to significantly impact outcomes for children with Ph+ ALL and allogeneic HCT with the best available donor should be encouraged in CR1.

  12. Screening for Y Chromosome Microdeletion in a Nonobstructive Azoospermic Male Patient with Allogeneic Bone Marrow Transplantation from His Sister

    Directory of Open Access Journals (Sweden)

    Hakan Gurkan

    2010-01-01

    Full Text Available Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells.

  13. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

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    Stephan Zaenker

    2011-01-01

    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  14. Dualism of mixed chimerism between hematopoiesis and stroma in chronic idiopathic myelofibrosis after allogeneic stem cell transplantation.

    Science.gov (United States)

    Thiele, J; Varus, E; Siebolts, U; Kvasnicka, H M; Wickenhauser, C; Metz, K A; Beelen, D W; Ditschkowski, M; Zander, A; Kröger, N

    2007-04-01

    Scant knowledge exists concerning lineage-restricted mixed chimerism (mCh) after allogeneic peripheral blood stem cell transplantation (PSCT) in patients with chronic idiopathic myelofibrosis (CIMF). Following a sex-mismatched PSCT, a combined immunopheno- and genotyping by fluorescence in-situ hybridization (FISH) was performed on sequential bone marrow (BM) biopsies at standardized intervals. Results were compared with PCR analysis of corresponding peripheral blood samples in five patients. According to FISH, pretransplant specimens revealed a gender congruence of more than 99%, while in the first three months the total BM exhibited a persistent fraction of host cells (30% to 40%) with a tendency to decline after about one year. It is noteworthy that the majority of endothelial cells maintained a recipient origin, whereas CD34+ progenitors and especially CD61+ megakaryocytes exhibited only very few host-derived cells. In keeping with the prevalence of donor cells in the hematopoietic compartment, PCR analysis of peripheral blood cells displayed a non-significant degree of mCh. In conclusion, according to FISH and PCR analysis, successful PSCT in CIMF results in an almost complete chimeric (donor-derived) state of the hematopoietic cell population. The non-transplantable stromal compartment includes the vascular endothelium with a predominance of recipient cells. The minimal mCh of this population implies probably a donor-derived origin (endothelial progenitor cells).

  15. Rationale and design of the SAIL trial for intramuscular injection of allogeneic mesenchymal stromal cells in no-option critical limb ischemia.

    Science.gov (United States)

    Wijnand, Joep G J; Teraa, Martin; Gremmels, Hendrik; van Rhijn-Brouwer, Femke C C; de Borst, Gert J; Verhaar, Marianne C

    2018-02-01

    Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and has an immense impact on quality of life, morbidity, and mortality. A considerable proportion of CLI patients are ineligible for revascularization, leaving amputation as the only option. Mesenchymal stromal cells (MSCs), because of their vasculoregenerative and immunomodulatory characteristics, have emerged as a potential new treatment. The primary objective of this trial is to investigate whether intramuscular administration of allogeneic bone marrow (BM)-derived MSCs is safe and potentially effective. The SAIL (allogeneic mesenchymal Stromal cells for Angiogenesis and neovascularization in no-option Ischemic Limbs) trial is a double-blind, placebo-controlled randomized clinical trial to investigate the effect of allogeneic BM-MSCs in patients with CLI who are not eligible for conventional revascularization. A total of 66 patients will be included and randomized (1:1) to undergo 30 intramuscular injections with either BM-MSCs (5 × 10 6 MSCs per injection) or placebo in the ischemic lower extremity. Primary outcome, that is, therapy success, a composite outcome consisting of mortality, limb status, clinical status, and changes in pain score, will be assessed at 6 months. All study-related procedures will take place in the University Medical Center Utrecht in The Netherlands. If our results indicate that intramuscular allogeneic BM-MSC therapy for CLI is safe and potentially effective, this will have important consequences for treatment of patients with CLI. A large multicenter clinical trial with longer follow-up focusing on hard end points should then be initiated to confirm these findings. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  16. A Long-Term Follow-Up Study of Allogeneic Mesenchymal Stem/Stromal Cell Transplantation in Patients with Drug-Resistant Systemic Lupus Erythematosus

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    Dandan Wang

    2018-03-01

    Full Text Available Summary: Allogeneic mesenchymal stem/stromal cells (MSCs have been widely studied as an alternative cell source for regenerative medicine. Here, we report a long-term follow-up study of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT in severe and drug-refractory systemic lupus erythematosus (SLE patients. Eighty-one patients were enrolled, and the 5-year overall survival rate was 84% (68/81 after MSCT. At 5-year follow-up, 27% of patients (22/81 were in complete clinical remission and another 7% (6/81 were in partial clinical remission, with a 5-year disease remission rate of 34% (28/81. In total, 37 patients had achieved clinical remission and then 9 patients subsequently relapsed, with 5-year overall rate of relapse of 24% (9/37. SLE Disease Activity Index scores, serum albumin, complement C3, peripheral white blood cell, and platelet numbers, as well as proteinuria levels, continued to improve during the follow-up. Our results demonstrated that allogeneic MSCT is safe and resulted in long-term clinical remission in SLE patients. : In this article, Sun and colleagues show that allogeneic bone marrow and/or umbilical cord-derived mesenchymal stem/stromal cell transplantation both result in good clinical safety and effect in treating drug-refractory systemic lupus erythematosus patients, by introducing a 5- to 8-year follow-up study for all the 81 enrolled patients. Keywords: bone marrow, mesenchymal stem cells, systemic lupus erythematosus, safety, umbilical cord

  17. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

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    Campana Dario

    2010-10-01

    Full Text Available Abstract Background The possibility that autologous NK cells could serve as an effective treatment modality for solid tumors has long been considered. However, implementation is hampered by (i the small number of NK cells in peripheral blood, (ii the difficulties associated with large-scale production of GMP compliant cytolytic NK cells, (iii the need to activate the NK cells in order to induce NK cell mediated killing and (iv the constraints imposed by autologous inhibitory receptor-ligand interactions. To address these issues, we determined (i if large numbers of NK cells could be expanded from PBMC and GMP compliant cell fractions derived by elutriation, (ii their ability to kill allogeneic and autologous tumor targets by direct cytotoxitiy and by antibody-mediated cellular cytotoxicity and (iii defined NK cell specific receptor-ligand interactions that mediate tumor target cell killing. Methods Human NK cells were expanded during 14 days. Expansion efficiency, NK receptor repertoire before and after expansion, expression of NK specific ligands, cytolytic activity against allogeneic and autologous tumor targets, with and without the addition of chimeric EGFR monoclonal antibody, were investigated. Results Cell expansion shifted the NK cell receptor repertoire towards activation and resulted in cytotoxicity against various allogeneic tumor cell lines and autologous gastric cancer cells, while sparing normal PBMC. Blocking studies confirmed that autologous cytotoxicity is established through multiple activating receptor-ligand interactions. Importantly, expanded NK cells also mediated ADCC in an autologous and allogeneic setting by antibodies that are currently being used to treat patients with select solid tumors. Conclusion These data demonstrate that large numbers of cytolytic NK cells can be generated from PBMC and lymphocyte-enriched fractions obtained by GMP compliant counter current elutriation from PBMC, establishing the preclinical

  18. Monitoring of a new approach of immunotherapy with allogenic 111In-labelled NK cells in patients with renal cell carcinoma

    International Nuclear Information System (INIS)

    Meller, Birgit; Lauer, Isabel; Schelper, Lutz F.; Hof, Katharina von; Richter, Eckart; Baehre, Manfred; Frohn, Christoph; Brand, Joerg-Matthias; Kirchner, Holger

    2004-01-01

    The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10 8 NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach. (orig.)

  19. Monitoring of a new approach of immunotherapy with allogenic {sup 111}In-labelled NK cells in patients with renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Meller, Birgit; Lauer, Isabel; Schelper, Lutz F.; Hof, Katharina von; Richter, Eckart; Baehre, Manfred [Clinic of Radiotherapy and Nuclear Medicine, University of Luebeck, Ratzeburger Allee 160, 23538, Luebeck (Germany); Frohn, Christoph; Brand, Joerg-Matthias; Kirchner, Holger [Institute of Immunology and Transfusion Medicine, University of Luebeck, Ratzeburger Allee 160, 23538, Luebeck (Germany)

    2004-03-01

    The transfusion of allogenic, in vitro expanded natural killer cells (NKC) is a novel therapy option in oncology. To date, however, the biodistribution and kinetics of allogenic NKC have not been investigated. Therefore, in this study three patients with renal cell carcinoma received 3-7 x 10{sup 8} NKC labelled with indium-111 oxine with a tenfold excess of unlabelled cells during NKC therapy. Whole-body scintigrams were obtained (0.5-144 h) in the anterior and posterior views. Scintigrams were analysed using a region of interest technique, and single-photon emission tomography (SPET) studies of the abdomen were performed. Results were compared to those obtained with polymerase chain reaction (PCR) of the peripheral blood (determination of foreign DNA, nested PCR, limit of detection 0.01%). Shortly after transfusion of NKC, more than 50% of the activity was accumulated in the lungs. We observed redistribution effects from lungs to liver, spleen and bone marrow. No significant loss of activity could be detected. In two of four large metastases, tracer accumulation could be proven by SPET. As confirmed by scintigrams and PCR, the fraction of circulating transfused cells was low at all times. Long-term activity retention might be caused either by survival of the allogenic cells, as confirmed by PCR (up to 3 days p.i.), or by phagocytosis of labelled cellular fragments. However, PCR data and uptake in metastases indicated long survival of a portion of allogenic NKC. Such long survival and low retention of the cells in the lung are requirements for an effective immunotherapeutic approach. (orig.)

  20. Pelvic reconstruction with allogeneic bone graft after tumor resection

    Science.gov (United States)

    Wang, Wei; Bi, Wen Zhi; Yang, Jing; Han, Gang; Jia, Jin Peng

    2013-01-01

    OBJECTIVES : Pelvic reconstruction after tumor resection is challenging. METHODS: A retrospective study had been preformed to compare the outcomes among patients who received pelvic reconstructive surgery with allogeneic bone graft after en bloc resection of pelvic tumors and patients who received en bloc resection only. RESULTS: Patients without reconstruction had significantly lower functional scores at 3 months (10 vs. 15, P = 0.001) and 6 months after surgery (18.5 vs. 22, P = 0.0024), a shorter duration of hospitalization (16 day vs. 40 days, P 0.05). CONCLUSIONS : Pelvic reconstruction with allogeneic bone graft after surgical management of pelvic tumors is associated with satisfactory surgical and functional outcomes. Further clinical studies are required to explore how to select the best reconstruction method. Level of Evidence IV, Case Series. PMID:24453659

  1. Single Cell HLA Matching Feasibility by Whole Genomic Amplification and Nested PCR

    Institute of Scientific and Technical Information of China (English)

    Xiao-hong Li; Fang-yin Meng

    2004-01-01

    @@ PCR based single-cell DNA analysis has been widely used in forensic science, preimplantation genetic diagnosis and so on. However, the original sample cannot be efficiently retrieved following single cell PCR, consequently the amount of information gained is limited. HLA system is too sophisticated that it is very hard to complete HLA typing by single cell. A Taq polymerase-based method using random primers to amplify whole genome termed as whole genome amplification (WGA) has demonstrated to be a useful method in increasing the copies of minimum sample. We establish a technique in this study to amplify HLA-A and HLA-B loci at same time in a single cell using WGA.

  2. Financial burden in recipients of allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Khera, Nandita; Chang, Yu-hui; Hashmi, Shahrukh; Slack, James; Beebe, Timothy; Roy, Vivek; Noel, Pierre; Fauble, Veena; Sproat, Lisa; Tilburt, Jon; Leis, Jose F; Mikhael, Joseph

    2014-09-01

    Although allogeneic hematopoietic cell transplantation (HCT) is an expensive treatment for hematological disorders, little is known about the financial consequences for the patients who undergo this procedure. We analyzed factors associated with its financial burden and its impact on health behaviors of allogeneic HCT recipients. A questionnaire was retrospectively mailed to 482 patients who underwent allogeneic HCT from January 2006 to June 2012 at the Mayo Clinic, to collect information regarding current financial concerns, household income, employment, insurance, out-of-pocket expenses, and health and functional status. A multivariable logistic regression analysis identified factors associated with financial burden and treatment nonadherence. Of the 268 respondents (56% response rate), 73% reported that their sickness had hurt them financially. All patients for whom the insurance information was available (missing, n = 13) were insured. Forty-seven percent of respondents experienced financial burden, such as household income decreased by >50%, selling/mortgaging home, or withdrawing money from retirement accounts. Three percent declared bankruptcy. Younger age and poor current mental and physical functioning increased the likelihood of financial burden. Thirty-five percent of patients reported deleterious health behaviors because of financial constraints. These patients were likely to be younger, have lower education, and with a longer time since HCT. Being employed decreased the likelihood of experiencing financial burden and treatment nonadherence due to concern about costs. A significant proportion of allogeneic HCT survivors experience financial hardship despite insurance coverage. Future research should investigate potential interventions to help at-risk patients and prevent adverse financial outcomes after this life-saving procedure. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Allogeneic stem cell transplantation in acute myeloid leukemia

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    Natasha Ali

    2012-11-01

    Full Text Available We report a case series of 12 patients with acute myeloid leukemia who underwent allogeneic stem cell transplant with a matched related donor. Male to female ratio was 1:1. The main complication post-transplant was graft-versus-host disease (n=7 patients. Transplant-related mortality involved one patient; cause of death was multi-organ failure. After a median follow up of 36.0±11.3 months, overall survival was 16%.

  4. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  5. Chimeric autologous/allogeneic constructs for skin regeneration.

    Science.gov (United States)

    Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

    2014-08-01

    The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  6. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

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    Shinichi Matsumoto

    2011-06-01

    Full Text Available Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities.

  7. Allogeneic Mesenchymal Stem Cell Treatment Induces Specific Alloantibodies in Horses

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    Sean D. Owens

    2016-01-01

    Full Text Available Background. It is unknown whether horses that receive allogeneic mesenchymal stem cells (MSCs injections develop specific humoral immune response. Our goal was to develop and validate a flow cytometric MSC crossmatch procedure and to determine if horses that received allogeneic MSCs in a clinical setting developed measurable antibodies following MSC administration. Methods. Serum was collected from a total of 19 horses enrolled in 3 different research projects. Horses in the 3 studies all received unmatched allogeneic MSCs. Bone marrow (BM or adipose tissue derived MSCs (ad-MSCs were administered via intravenous, intra-arterial, intratendon, or intraocular routes. Anti-MSCs and anti-bovine serum albumin antibodies were detected via flow cytometry and ELISA, respectively. Results. Overall, anti-MSC antibodies were detected in 37% of the horses. The majority of horses (89% were positive for anti-bovine serum albumin (BSA antibodies prior to and after MSC injection. Finally, there was no correlation between the amount of anti-BSA antibody and the development of anti-MSC antibodies. Conclusion. Anti allo-MSC antibody development was common; however, the significance of these antibodies is unknown. There was no correlation between either the presence or absence of antibodies and the percent antibody binding to MSCs and any adverse reaction to a MSC injection.

  8. Reduction in requirements for allogeneic blood products: nonpharmacologic methods.

    Science.gov (United States)

    Hardy, J F; Bélisle, S; Janvier, G; Samama, M

    1996-12-01

    Various strategies have been proposed to decrease bleeding and allogeneic transfusion requirements during and after cardiac operations. This article attempts to document the usefulness, or lack thereof, of the nonpharmacologic methods available in clinical practice. Blood conservation methods were reviewed in chronologic order, as they become available to patients during the perisurgical period. The literature in support of or against each strategy was reexamined critically. Avoidance of preoperative anemia and adherence to published guidelines for the practice of transfusion are of paramount importance. Intraoperatively, tolerance of low hemoglobin concentrations and use of autologous blood (predonated or harvested before bypass) will reduce allogeneic transfusions. The usefulness of plateletpheresis and retransfusion of shed mediastinal fluid remains controversial. Intraoperatively and postoperatively, maintenance of normothermia contributes to improved hemostasis. Several approaches have been shown to be effective. An efficient combination of methods can reduce, and sometimes abolish, the need for allogeneic blood products after cardiac operations, inasmuch as all those involved in the care of cardiac surgical patients adhere thoughtfully to existing transfusion guidelines.

  9. ALLOGENEIC STEM CELL TRANSPLANTATION FOR ADULT PATIENTS WITH ACUTE LEUKEMIA – 14 YEARS EXPERIENCE

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    Jože Pretnar

    2004-12-01

    Full Text Available Background. This study was designed to evaluate the impact of various prognostic factors on long-term survival and event free survival after allogeneic hematopoietic stem cell transplantation for patients with acute leukemia.Methods and patients. Between years 1989 and 2002 44 patients with acute leukemia (30 with AML and 14 with ALL were transplanted. Survival curves using the Kaplan-Meier method were calculated for patients transplanted with two different sources of stem cells – bone marrow and peripheral blood and separately for patients with female donor.Results. Estimated 10 years survival for AML is 43% and 64% for ALL patients which is not statistically different. There are no significant differences in outcome regarding source of stem cells and in donors’ gender.Conclusions. To conclude, our results show that neither source of stem cells nor donor’s gender has impact on the long-term survival after hematopoietic stem cell transplantation. As published previously patients transplanted beyond the first remission have significantly worse outcome.

  10. Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells

    International Nuclear Information System (INIS)

    Yasumizu, R.; Onoe, K.; Iwabuchi, K.; Ogasawara, M.; Fujita, M.; Okuyama, H.; Good, R.A.; Morikawa, K.

    1985-01-01

    Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study

  11. Split tolerance in nude mice transplanted with 2'-deoxyguanosine-treated allogeneic thymus lobes

    International Nuclear Information System (INIS)

    Suzuki, G.; Moriyama, T.; Takeuchi, Y.; Kawase, Y.; Habu, S.

    1989-01-01

    To elucidate the acquisition of self tolerance in the thymus, full-allogeneic thymic chimeras were constructed. Athymic C3H and BALB/c nude mice were reconstituted with the thymic lobes of BALB/c and B10.BR fetuses, respectively, that were organ cultured for 5 days in the presence of 2'-deoxyguanosine. T cells in these chimeras were tolerized to the host MHC in both MLR and CTL assays. In contrast, T cells in the chimeras exhibited split tolerance for the thymic MHC haplotype. CTL specific for class I MHC of the thymic haplotype were generated not only from the peripheral T cells of the chimeras but also from thymocytes re-populated in the engrafted thymic lobes. However, T cells in these chimeras responded poorly to the class II MHC of the thymic haplotype in a standard MLR assay. In a syngeneic MLR culture upon stimulation with enriched APC of the thymic haplotype, only 22 to 48% of the responses were mediated by CD4+ cells, and proliferations of CD4- cells were prominent. There were no haplotype-specific suppressor cells detected which would cause the unresponsiveness to the thymic class II MHC. These results indicated that the thymic lobes treated with 2'-deoxyguanosine were defective in the ability to induce the transplantation tolerance for the class I MHC expressed on the thymus, although the same thymic lobes were able to induce the transplantation tolerance for the thymic class II MHC

  12. Patients with Multiple Myeloma Develop SOX2-Specific Autoantibodies after Allogeneic Stem Cell Transplantation

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    Sebastian Kobold

    2011-01-01

    Full Text Available The occurrence of SOX2-specific autoantibodies seems to be associated with an improved prognosis in patients with monoclonal gammopathy of undetermined significance (MGUS. However, it is unclear if SOX2-specific antibodies also develop in established multiple myeloma (MM. Screening 1094 peripheral blood (PB sera from 196 MM patients and 100 PB sera from healthy donors, we detected SOX2-specific autoantibodies in 7.7% and 2.0% of patients and donors, respectively. We identified SOX2211–230 as an immunodominant antibody-epitope within the full protein sequence. SOX2 antigen was expressed in most healthy tissues and its expression did not correlate with the number of BM-resident plasma cells. Accordingly, anti-SOX2 immunity was not related to SOX2 expression levels or tumor burden in the patients’ BM. The only clinical factor predicting the development of anti-SOX2 immunity was application of allogeneic stem cell transplantation (alloSCT. Anti-SOX2 antibodies occurred more frequently in patients who had received alloSCT (n=74. Moreover, most SOX2-seropositive patients had only developed antibodies after alloSCT. This finding indicates that alloSCT is able to break tolerance towards this commonly expressed antigen. The questions whether SOX2-specific autoantibodies merely represent an epiphenomenon, are related to graft-versus-host effects or participate in the immune control of myeloma needs to be answered in prospective studies.

  13. Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

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    Irene Riezzo

    2017-01-01

    Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

  14. A new method of prefabricated vascularized allogenic bone grafts for maxillo-mandibular reconstruction

    International Nuclear Information System (INIS)

    Pill-Hoon Choung

    1999-01-01

    Although there are various applications of allogenic bone grafts, a new technique of prevascularized lyophilized allogenic bone grafting for maxillo-mandibular reconstruction will be presented. Allogenic bone has been made by author's protocol for jaw defects as a powder, chip or block bone type. The author used lyophilized allogenic bone grafts for discontinuity defects as a block bone. In those cases, neovascularization and resorption of the allogenic bone were important factors for success of grafting. To overcome the problems, the author designed the technique of prefabricated vascularization of allogenic bone, which was lyophilized cranium, with an application of bovine BMP or not. Lyophilized cranial bone was designed for the defects and was put into the scalp. After confirming a hot spot via scintigram several months later, vascularized allogenic bone was harvested pedicled on the parietotemporal fascia based on the superficial temporal artery and vein. Vascularized allogenic cranial bone was rotated into the defect and fixed rigidly. Postoperatively, there was no severe resorption and functional disturbance of the mandible. In this technique, BMP seems to be an important role to help osteogenesis and neovascularization. Eight patients underwent prefabricated vascularization of allogenic bone grafts. Among them, four cases of reconstruction in mandibular discontinuity defects and one case of reconstruction in maxillectomy defect underwent this method, which will be presented with good results. This method may be an alternative technique of microvascular free bone graft

  15. Vasculitic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Mona Amini

    2014-02-01

    Full Text Available Primary systemic vasculitis in pre-capillary arteries is associated with peripheral neuropathy. In some types of systematic vasculitis about 60 % of patients have peripheral nervous system (PNS involvement. In vasculitic peripheral neuropathies (VPN a necrotizing and inflammatory process leads to narrowing of vasa nervorum lumen and eventually the appearance of ischemic lesions in peripheral nerves. Some features might be suggestive of VPN, like: axonal nerve degeneration, wallerian-like degeneration, and diameter irregularity of nerve. Peripheral nervous system (PNS destruction during systemic vasculitides should be considered, due to its frequency and early occurrence in vasculitis progression. The first line treatment of non systematic VPNs is corticosteroid agents, but these drugs might worsen the VPNs or systemic vasculitis.

  16. Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

    International Nuclear Information System (INIS)

    Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

    1975-01-01

    Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

  17. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  18. Peripheral Neuropathy: Symptoms and Signs

    Science.gov (United States)

    ... Utah Research News Make a Difference Symptoms of Peripheral Neuropathy Print This Page Peripheral Neuropathy symptoms usually start ... more slowly over many years. The symptoms of peripheral neuropathy often include: A sensation of wearing an invisible “ ...

  19. The use of cytokine-stimulated healthy donors in allogeneic stem cell transplantation.

    Science.gov (United States)

    Cesaro, Simone; Marson, Piero; Gazzola, Maria Vittoria; De Silvestro, Giustina; Destro, Roberta; Pillon, Marta; Calore, Elisabetta; Messina, Chiara; Zanesco, Luigi

    2002-08-01

    Treatment of healthy donors with recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows the mobilization and peripheralization into circulating blood of an adequate number of CD34+ cells that can then be collected by leukapheresis (PBSC). This procedure avoids the invasiveness of bone marrow harvest and the risks related to general anesthesia. The main adverse effects of rhG-CSF are: bone pain, 84%, headache, 54%, fatigue, 31%, and nausea, 13%, which are usually scored by the donors as moderate to severe, resolving within 2-3 days after discontinuation of the cytokine. Analgesics, mainly acetaminophen, are sufficient to control the pain. Less than 5% of the donors experience non-cardiac chest pain, a local reaction at the injection site, insomnia, dizziness or a low-grade fever. Discontinuation of the PBSC procedure because of adverse effects of rhG-CSF or leukapheresis is rarely necessary (0.5%) but this good tolerability can be hampered by the need, in 5-20% of cases, for an adequate venous access that requires insertion of a central or venous catheter. There are no absolute contraindications to the stimulation of healthy donors with rhG-CSF but the description of cases of non-traumatic splenic rupture, iritis, cardiac ischemia, and gouty arthritis suggests that further precautionary restrictions are advisable when deciding eligibility for PBSC collection. The main advantages for patients receiving an allogeneic PBSC transplant are the faster hematologic and immunologic recovery and the potential for a greater efficacy in advanced disease by lowering the transplant-related mortality. One of the major concerns regarding the use of rhG-CSF in unrelated healthy donors is the uncertainty about its possible role in triggering malignancy, in particular myelodysplastic syndrome and acute myeloid leukemia. There are no studies with an adequate sample size and follow-up that can answer this question but two recent retrospective studies reported that in

  20. Peripheral Ulcerative Keratitis

    Science.gov (United States)

    ... oval in shape. Diagnosis A doctor's evaluation Sometimes culture The diagnosis of peripheral ulcerative keratitis is suspected when the doctor sees the affected cornea in a person who also has a severe and/or long- ...

  1. Tumors of peripheral nerves

    International Nuclear Information System (INIS)

    Ho, Michael; Lutz, Amelie M.

    2017-01-01

    Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

  2. Promoting peripheral myelin repair

    OpenAIRE

    Zhou, Ye; Notterpek, Lucia

    2016-01-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

  3. Impact of stem cell source on allogeneic stem cell transplantation outcome in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Stamatović Dragana

    2011-01-01

    Full Text Available Background/Aim. Peripheral blood (PB is used more frequently as a source of stem cells (SCs for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT with bone marrow transplantation (BMT on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease - aGvHD and delayed (chronic GvHD - cGvHD complications, as well as transplant-related mortality (TRM, transfusion needs, relapses and overall survival (OS. Methods. We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57, who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML - 39, acute lymphoblastic leukemia (ALL - 47, chronic myeloid leukemia (CML - 32, myelodysplastic syndrome (MDS - 10, Hodgkin’s lymphoma (HL - 2, multiple myeloma (MM - 3, granulocytic sarcoma (GrSa - 3, severe aplastic anemia (sAA - 22. The patients underwent transplantations were divided into two groups: BMT group (74 patients and PBSCT group (84 patients. Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one “Large Volume Leukapheresis” (after recombinant human granulocyte colony stimulating factor, rHuG-CSF application (5-12 μg/kgbm, 5 days. Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001 faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (p < 0.01 higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05. There were

  4. RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

    Directory of Open Access Journals (Sweden)

    N. V. Purlo

    2014-01-01

    Full Text Available We report the case of successful renal allogeneic transplantation and treatment in a 56-year-old patient with haemophilia B at Hematology Research Center. He has received replacement therapy by factor IX since 2010. The transplant is marked with good renal function during 13 post-transplant months without episodes of rejection or bleeding complications. The complicated surgical interventions are possible in patients with haemophilia В аnd end-stage chronic renal failure in the presence of replacement therapy of IX factor for the purpose of achievement of optimum hemostasis.

  5. Identification of high-risk patients with aplastic anaemia in selection for allogeneic 0one-marrow transplantation.

    Science.gov (United States)

    Lohrmann, H P; Kern, P; Niethammer, D; Heimpel, H

    1976-09-25

    Of 75 patients with asplastic anaemia treated between 1968 and 1975, 33 were retrospectively considered as potential candidates for allogenegic bone-marrow transplantation on the basis of their age and severity of marrow failure. The prognosis of these patients with conservative treatment was assessed from parameters obtained at the time of the initial diagnosis. Initial peripheral-blood granulocyte or platelet concentrations were not of porgnostic value. In contrast, initial reticulocyte concentrations, allowed separation of the patients into two groups with poor and good prognosis. Low initial reticulocyte concentrations (less than 10 000/mu1) indicated those patients at extremely high risk of succumbing to their marrow aplasia (there were no survivors 36 months after disgnosis). In contrast, 75% of those patients with more than 10 000 reticulocytes per mu1 at diagnosis survived for 3 years. Initial peripheral-blood reticulocyte concentrations thus appear to indicate the extent of the marrow failure in aplastic anaemia more accurately than granulocytes or platelets. Low initial reticulocyte concentrations may indicate, among patients with severe aplastic anaemia, those for whom allogeneic bone-marrow transplantation should be seriously considered; patients with higher initial reticulocyte concentrations may benefit from conservation treatment.

  6. Allograft immunity in vitro. I. Cultivation conditions and mixed lymphocyte interaction of mouse peripheral lymphocytes

    Science.gov (United States)

    Häyry, P.; Defendi, V.

    1970-01-01

    We have adapted mouse peripheral lymphocytes to culture as a preliminary step in designing a model for the study of allograft immunity in vitro. The isolation of peripheral leucocytes is facilitated by using Plasmagel® as an erythrocyte-agglutinating agent. The yield of leucocytes can be considerably increased by intravenous injection of the donor animals with supernatant fluid from Bordetella pertussis cultures and the lymphocytes thus mobilized react both to phytohaemagglutinin (PHA) and allogeneic stimulus, as do lymphocytes from untreated animals. Preparations which contain more than 25–50 RBC/WBC are refractory in the mixed lymphocyte interaction (MLI). The optimum cell density for the proliferative response is approximately 1–3 × 106 lymphocytes/ml. Various nutritive milieu were tested and found to have little influence on the MLI; both normal and suspension media behaved in a similar manner. PHA causes a vigorous proliferative response in mouse peripheral lymphocytes, the 3H–TdR incorporation values in PHA-containing cultures at peak point of stimulation (3rd day) being up to 1000 times those observed for control cultures. The allogeneic response in the MLI takes place later (6th to 7th day) and is weaker, about one-tenth the PHA response, when strains differing at the H-2 locus are used as cell donors. Because the specific proliferative response to allogeneic stimulus in mixed culture, regardless of the way it is measured, is indistinguishable from the response produced by other non-specific factors, these other factors must be critically excluded. It appears that supplementing the culture medium with low concentrations of certain lots of foetal calf or agamma-newborn-calf serum permits the study of the specific response at an optimum sensitivity. PMID:4315207

  7. CFU-C populations in blood and bone marrow of dogs after lethal irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells

    International Nuclear Information System (INIS)

    Nothdurft, W.; Fliedner, T.M.; Calvo, W.; Flad, H.-D.; Huget, R.; Koerbling, M.; Krumbacher-von Loringen, K; Ross, W.M.; Schnappauf, H.-P.; Steinbach, I.

    1978-01-01

    Colony forming units in agar (CFU-C) were assayed in both bone marrow and peripheral blood of dogs during haemopoietic recovery after lethal total-body irradiation (1200 R) and allogeneic transfusion of blood mononuclear cells (MNC) from histocompatible donors. MNC had been collected from the peripheral blood by continuous-flow centrifugation leucapheris and cryopreserved at -196 deg C until transfusion. Two groups of dogs were studied. Group 1 dogs (n = 12) were given between 0.39 and 2.76 x 10 9 MNC per kg body wt. Group 2 dogs (n = 14) were transfused with a similar number of MNC, ranging from 0.51 to 1.87 x 10 9 per kg body wt., but in addition underwent immuno-suppressive therapy with methotrexate. In group 1 dogs, there was a rather good correlation between the number of CFU-C in the regenerating bone marrow and the recovery of the peripheral blood granulocyte values. The regeneration of the CPU-C population in the bone marrow of methotrexate-treated dogs showed a somewhat more heterogeneous picture than in dogs of group 1 and in dogs that, in a previous study, were transfused with autologous MNC. The minimum time interval required for the reconstitution of peripheral blood CFU-C to normal levels was 2-4 weeks but usually took from 4-14 weeks. (author)

  8. Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

    International Nuclear Information System (INIS)

    Tulunay, O.; Good, R.A.; Yunis, E.J.

    1975-01-01

    After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

  9. Decreased HIV diversity after allogeneic stem cell transplantation of an HIV-1 infected patient: a case report

    Directory of Open Access Journals (Sweden)

    Thielen Alexander

    2010-03-01

    Full Text Available Abstract The human immunodeficiency virus type 1 (HIV-1 coreceptor use and viral evolution were analyzed in blood samples from an HIV-1 infected patient undergoing allogeneic stem cell transplantation (SCT. Coreceptor use was predicted in silico from sequence data obtained from the third variable loop region of the viral envelope gene with two software tools. Viral diversity and evolution was evaluated on the same samples by Bayesian inference and maximum likelihood methods. In addition, phenotypic analysis was done by comparison of viral growth in peripheral blood mononuclear cells and in a CCR5 (R5-deficient T-cell line which was controlled by a reporter assay confirming viral tropism. In silico coreceptor predictions did not match experimental determinations that showed a consistent R5 tropism. Anti-HIV directed antibodies could be detected before and after the SCT. These preexisting antibodies did not prevent viral rebound after the interruption of antiretroviral therapy during the SCT. Eventually, transplantation and readministration of anti-retroviral drugs lead to sustained increase in CD4 counts and decreased viral load to undetectable levels. Unexpectedly, viral diversity decreased after successful SCT. Our data evidence that only R5-tropic virus was found in the patient before and after transplantation. Therefore, blocking CCR5 receptor during stem cell transplantation might have had beneficial effects and this might apply to more patients undergoing allogeneic stem cell transplantation. Furthermore, we revealed a scenario of HIV-1 dynamic different from the commonly described ones. Analysis of viral evolution shows the decrease of viral diversity even during episodes with bursts in viral load.

  10. Bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: phenotypes and prognosis.

    Science.gov (United States)

    Bergeron, A; Godet, C; Chevret, S; Lorillon, G; Peffault de Latour, R; de Revel, T; Robin, M; Ribaud, P; Socié, G; Tazi, A

    2013-06-01

    Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic SCT (HSCT) is recognized as a new-onset obstructive lung defect (OLD) in pulmonary function testing and is related to pulmonary chronic GVHD. Little is known about the different phenotypes of patients with BOS and their outcomes. We reviewed the data of all allogeneic HSCT recipients referred to our pulmonary department for a non-infectious bronchial disease between 1999 and 2010. We identified 103 patients (BOS (n=77), asthma (n=11) and chronic bronchitis (n=15)). In patients with BOS, we identified two functional phenotypes: a typical OLD, that is, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 (n=53), and an atypical OLD with a concomitant decrease in the FEV1 <80% and FVC <80% predicted with a normal total lung capacity (n=24). The typical OLD was characterized by more severe FEV1 and fewer centrilobular nodules on the computed tomography scan. The FEV1 was not significantly affected during the follow-up, regardless of the phenotype. In addition to acute and extensive chronic GVHD, only the occurrence of BOS soon after transplantation and the intentional treatment of BOS with steroids were associated with a poor survival. The determination of patient subgroups should be explored to improve the management of this condition.

  11. Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Hanajiri, Ryo; Kobayashi, Takeshi; Yoshioka, Kosuke; Watanabe, Daisuke; Watakabe, Kyoko; Murata, Yutaka; Hagino, Takeshi; Seno, Yasushi; Najima, Yuho; Igarashi, Aiko; Doki, Noriko; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2017-03-01

    Here, we described the clinical characteristics and outcomes of central nervous system (CNS) infections occurring after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a single institution over the previous 6 years. Charts of 353 consecutive allogeneic transplant recipients were retrospectively reviewed for CNS infection. A total of 17 cases of CNS infection were identified at a median of 38 days (range, 10-1028 days) after allo-HSCT. Causative pathogens were human herpesvirus-6 (n=6), enterococcus (n=2), staphylococcus (n=2), streptococcus (n=2), varicella zoster virus (n=1), cytomegalovirus (n=1), John Cunningham virus (n=1), adenovirus (n=1), and Toxoplasma gondii (n=1). The cumulative incidence of CNS infection was 4.1% at 1 year and 5.5% at 5 years. Multivariate analysis revealed that high-risk disease status was a risk factor for developing CNS infection (p=.02), and that overall survival at 3 years after allo-HSCT was 33% in patients with CNS infection and 53% in those without CNS infection (p=.04). Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  12. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Francesco Orio

    2014-01-01

    Full Text Available Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo- and autologous- (auto- stem cell transplant (HSCT. This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma, gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

  13. Allogenic blood transfusion following total hip arthroplasty: results from the nationwide inpatient sample, 2000 to 2009.

    Science.gov (United States)

    Saleh, Anas; Small, Travis; Chandran Pillai, Aiswarya Lekshmi Pillai; Schiltz, Nicholas K; Klika, Alison K; Barsoum, Wael K

    2014-09-17

    The large-scale utilization of allogenic blood transfusion and its associated outcomes have been described in critically ill patients and those undergoing high-risk cardiac surgery but not in patients undergoing elective total hip arthroplasty. The objective of this study was to determine the trends in utilization and outcomes of allogenic blood transfusion in patients undergoing primary total hip arthroplasty in the United States from 2000 to 2009. An observational cohort of 2,087,423 patients who underwent primary total hip arthroplasty from 2000 to 2009 was identified in the Nationwide Inpatient Sample. International Classification of Diseases, Ninth Revision, Clinical Modification procedure codes 99.03 and 99.04 were used to identify patients who received allogenic blood products during their hospital stay. Risk factors for allogenic transfusions were identified with use of multivariable logistic regression models. We used propensity score matching to estimate the adjusted association between transfusion and surgical outcomes. The rate of allogenic blood transfusion increased from 11.8% in 2000 to 19.0% in 2009. Patient-related risk factors for receiving an allogenic blood transfusion include an older age, female sex, black race, and Medicaid insurance. Hospital-related risk factors include rural location, smaller size, and non-academic status. After adjusting for confounders, allogenic blood transfusion was associated with a longer hospital stay (0.58 ± 0.02 day; p conservation methods. Copyright © 2014 by The Journal of Bone and Joint Surgery, Incorporated.

  14. Allogeneic CD19-CAR-T cell infusion after allogeneic hematopoietic stem cell transplantation in B cell malignancies.

    Science.gov (United States)

    Liu, Jun; Zhong, Jiang F; Zhang, Xi; Zhang, Cheng

    2017-01-31

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the cornerstone in treatment of hematological malignancies. However, relapse of the hematological disease after allo-HSCT remains a challenge and is associated with poor long-term survival. Chimeric antigen receptor redirected T cells (CAR-T cells) can lead to disease remission in patients with relapsed/refractory hematological malignancies. However, the therapeutic window for infusion of CAR-T cells post allo-HSCT and its efficacy are debatable. In this review, we first discuss the use of CAR-T cells for relapsed cases after allo-HSCT. We then review the toxicities and the occurrence of graft-versus-host disease in relapsed patients who received CAR-T cells post allo-HSCT. Finally, we review clinical trial registrations and the therapeutic time window for infusion of CAR-T cells post allo-HSCT. The treatment of allogeneic CAR-T cells is beneficial for patients with relapsed B cell malignancies after allo-HSCT with low toxicities and complications. However, multicenter clinical trials with larger sample sizes should be performed to select the optimal therapeutic window and confirm its efficacy.

  15. Peripheral epithelial odontogenic tumor

    International Nuclear Information System (INIS)

    Carzoglio, J.; Tancredi, N.; Capurro, S.; Ravecca, T.; Scarrone, P.

    2006-01-01

    A new case of peripheral epithelial odontogenic tumor (Pindborg tumor) is reported. It is localized in the superior right gingival region, a less frequent site, and has the histopathological features previously reported. Immunochemical studies were performed, revealing a differential positive stain to cytokeratins in tumor cells deeply seated in the tumor mass, probably related to tumoral cell heterogeneity.Interestingly, in this particular case S-100 protein positive reactivity was also detected in arborescent cells intermingled with tumoral cells, resembling Langerhans cells. Even though referred in the literature in central Pindborg tumors, no references were found about their presence in peripheral tumors, like the one that is presented here

  16. Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT.

    Science.gov (United States)

    Ryan, Christine E; Sahaf, Bita; Logan, Aaron C; O'Brien, Susan; Byrd, John C; Hillmen, Peter; Brown, Jennifer R; Dyer, Martin J S; Mato, Anthony R; Keating, Michael J; Jaglowski, Samantha; Clow, Fong; Rezvani, Andrew R; Styles, Lori; Coutre, Steven E; Miklos, David B

    2016-12-22

    Ibrutinib, a potent and irreversible small-molecule inhibitor of both Bruton's tyrosine kinase and interleukin-2 inducible kinase (ITK), has been used to treat relapsed/refractory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival. Here, we present 27 patients with relapsed CLL following allogeneic hematopoietic cell transplant (HCT) who subsequently received ibrutinib salvage therapy. Sixteen of these patients were part of multi-institutional clinical trials and achieved an overall response rate of 87.5%. An additional 11 patients were treated at Stanford University following US Food and Drug Administration approval of ibrutinib; 7 (64%) achieved a complete response, and 3 (27%) achieved a partial response. Of the 9 patients treated at Stanford who had mixed chimerism-associated CLL relapse, 4 (44%) converted to full donor chimerism following ibrutinib initiation, in association with disease response. Four of 11 (36%) patients evaluated by ClonoSeq achieved minimal residual disease negativity with CLL ibrutinib was discontinued, in 1 case even after 26 months. None of the 27 patients developed graft-versus-host-disease (GVHD) following ibrutinib initiation. We postulate that ibrutinib augments the graft-versus-leukemia (GVL) benefit through a T-cell-mediated effect, most likely due to ITK inhibition. To investigate the immune modulatory effects of ibrutinib, we completed comprehensive immune phenotype characterization of peripheral B and T cells from treated patients. Our results show that ibrutinib selectively targets pre-germinal B cells and depletes Th2 helper cells. Furthermore, these effects persisted after drug discontinuation. In total, our results provide evidence that ibrutinib effectively augments GVL without causing GVHD. © 2016 by The American Society of Hematology.

  17. Peripheral Artery Disease

    Science.gov (United States)

    ... pressure High blood cholesterol Coronary heart disease Stroke Metabolic syndrome Screening and Prevention Taking action to control your risk factors can help prevent or delay peripheral artery disease (P.A.D.) and its complications. Know your family history of health problems related to P.A. ...

  18. Promoting peripheral myelin repair.

    Science.gov (United States)

    Zhou, Ye; Notterpek, Lucia

    2016-09-01

    Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Immune competence in /sup 90/Sr-exposed, adult thymectomized and antilymphocyteglobulin-treated CBA mice. Pt. 1. Allogenic skin graft reaction

    Energy Technology Data Exchange (ETDEWEB)

    Bierke, P.

    1989-01-01

    CBA mice subjected to either adult thymectomy, internal exposure to /sup 90/Sr or antilymphocyteglobulin treatment separately, or to combinations of the three were tested for cellular immune competence using their reaction to allogenic skin grafts. Peripheral blood white cell counts did not reveal any obvious correlation between the degree of mononuclear cell depletion and the ability to accept grafts, suggesting that the particular treatments depleted specific fractions of mononuclear cells, differing in their extent of involvement in the rejection process. No single treatment alone induced a significant prolongation in the time elapsed before graft rejection. Adult thymectomy followed by appropriate antilymphocyteglobulin treatment induced severe lymphocytopenia and a profound suppression of the cell-mediate immune system, as evidenced by the acceptance of allogenic skin grafts. When applied to /sup 90/Sr-preexposed mice the same treatment induced lifelong acceptance of grafts, indicating a similar, though weaker immunosuppressive impact of /sup 90/Sr. Hence it was possible to significantly enhance immunosuppression in /sup 90/Sr-exposed mice. This in vivo model should be useful when investigating the role of immunological responsiveness in radiation carcinogenesis. (orig.).

  20. Combined use of decellularized allogeneic artery conduits with autologous transdifferentiated adipose-derived stem cells for facial nerve regeneration in rats.

    Science.gov (United States)

    Sun, Fei; Zhou, Ke; Mi, Wen-juan; Qiu, Jian-hua

    2011-11-01

    Natural biological conduits containing seed cells have been widely used as an alternative strategy for nerve gap reconstruction to replace traditional nerve autograft techniques. The purpose of this study was to investigate the effects of a decellularized allogeneic artery conduit containing autologous transdifferentiated adipose-derived stem cells (dADSCs) on an 8-mm facial nerve branch lesion in a rat model. After 8 weeks, functional evaluation of vibrissae movements and electrophysiological assessment, retrograde labeling of facial motoneurons and morphological analysis of regenerated nerves were performed to assess nerve regeneration. The transected nerves reconstructed with dADSC-seeded artery conduits achieved satisfying regenerative outcomes associated with morphological and functional improvements which approached those achieved with Schwann cell (SC)-seeded artery conduits, and superior to those achieved with artery conduits alone or ADSC-seeded artery conduits, but inferior to those achieved with nerve autografts. Besides, numerous transplanted PKH26-labeled dADSCs maintained their acquired SC-phenotype and myelin sheath-forming capacity inside decellularized artery conduits and were involved in the process of axonal regeneration and remyelination. Collectively, our combined use of decellularized allogeneic artery conduits with autologous dADSCs certainly showed beneficial effects on nerve regeneration and functional restoration, and thus represents an alternative approach for the reconstruction of peripheral facial nerve defects. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. G-CSF-primed BM for allogeneic SCT: revisited.

    Science.gov (United States)

    Pessach, I; Resnick, I; Shimoni, A; Nagler, A

    2015-07-01

    G-SCF-mobilized PBSC (GPB) grafts have a higher cell dose and somewhat more committed progenitor cells than steady-state BM (SBM), resulting in faster engraftment and faster immunological reconstitution. On the other hand, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) are similar both for PB and for BM. In contrast to SBM, G-CSF-primed BM (GBM) grafts stimulate HSC proliferation, increasing cell dose and thus resulting in faster engraftment because of higher cell dose infused, or because of treatment with G-CSF. Furthermore, GBM may induce tolerance and functional modulations in donor hematopoiesis and immunity, further reducing GVHD incidence, which is already lower with SBM compared with GPB grafts. Overall, a growing body of clinical evidence suggests that GBM transplants may share the advantages of GPB transplantations, without the associated increased risk of GVHD, and might be an attractive graft source for allogeneic SCTs.

  2. How and when I do allogeneic transplant in CLL.

    Science.gov (United States)

    Gribben, John G

    2018-05-11

    Allogenic stem cell transplantation (allo-SCT) has been considered the treatment of choice for high-risk patients with chronic lymphocytic leukemia (CLL) and the only approach offered with curative intent in this disease. The availability novel agents including the B cell receptor inhibitors (BCRi) ibrutinib, acalabrutinib and idelalisib, as well as venetoclax which targets the BCL2 pathway and the success of these agents in treating high-risk disease patients has made it more difficult to assess who and when in their treatment course allo-SCT should be considered. In this review, I will discuss the different treatment options available for the treatment of high-risk CLL and how allo-SCT fits into the treatment algorithm in the era of novel agents. Copyright © 2018 American Society of Hematology.

  3. Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Ogonek, Justyna; Kralj Juric, Mateja; Ghimire, Sakhila; Varanasi, Pavankumar Reddy; Holler, Ernst; Greinix, Hildegard; Weissinger, Eva

    2016-01-01

    The timely reconstitution and regain of function of a donor-derived immune system is of utmost importance for the recovery and long-term survival of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Of note, new developments such as umbilical cord blood or haploidentical grafts were associated with prolonged immunodeficiency due to delayed immune reconstitution, raising the need for better understanding and enhancing the process of immune reconstitution and finding strategies to further optimize these transplant procedures. Immune reconstitution post-HSCT occurs in several phases, innate immunity being the first to regain function. The slow T cell reconstitution is regarded as primarily responsible for deleterious infections with latent viruses or fungi, occurrence of graft-versus-host disease, and relapse. Here we aim to summarize the major steps of the adaptive immune reconstitution and will discuss the importance of immune balance in patients after HSCT. PMID:27909435

  4. In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3-4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

    International Nuclear Information System (INIS)

    Witherspoon, R.P.; Lum, L.G.; Storb, R.; Thomas, E.D.

    1982-01-01

    Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA-haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease

  5. Allogeneic epidermal substitutes in the treatment of chronic diabetic leg and foot ulcers

    Directory of Open Access Journals (Sweden)

    Andrea Marchesi

    2014-09-01

    Full Text Available Aim: Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world. Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care. New allogeneic sheets are available for the management of diabetic leg and foot ulcers. Methods: The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus. Results: Between 21 and 70 days after cellular therapy, 6 out of 16 lesions were completely healed, reducing the wound dimension by 70% and improving the wound bed score by 52%. Conclusion: The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.

  6. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials.

    Science.gov (United States)

    Srivatsan, Sanjay; Patel, Jaina M; Bozeman, Erica N; Imasuen, Imade E; He, Sara; Daniels, Danielle; Selvaraj, Periasamy

    2014-01-01

    The high mortality rate associated with cancer and its resistance to conventional treatments such as radiation and chemotherapy has led to the investigation of a variety of anti-cancer immunotherapies. The development of novel immunotherapies has been bolstered by the discovery of tumor-associated antigens (TAAs), through gene sequencing and proteomics. One such immunotherapy employs established allogeneic human cancer cell lines to induce antitumor immunity in patients through TAA presentation. Allogeneic cancer immunotherapies are desirable in a clinical setting due to their ease of production and availability. This review aims to summarize clinical trials of allogeneic tumor immunotherapies in various cancer types. To date, clinical trials have shown limited success due potentially to extensive degrees of inter- and intra-tumoral heterogeneity found among cancer patients. However, these clinical results provide guidance for the rational design and creation of more effective allogeneic tumor immunotherapies for use as monotherapies or in combination with other therapies.

  7. Current status of grafts and implants in rhinoplasty: Part II. Homologous grafts and allogenic implants.

    Science.gov (United States)

    Sajjadian, Ali; Naghshineh, Nima; Rubinstein, Roee

    2010-03-01

    After reading this article, the participant should be able to: 1. Understand the challenges in restoring volume and structural integrity in rhinoplasty. 2. Identify the appropriate uses of various homologous grafts and allogenic implants in reconstruction, including: (a) freeze-dried acellular allogenic cadaveric dermis grafts, (b) irradiated cartilage grafts, (c) hydroxyapatite mineral matrix, (d) silicone implants, (e) high-density polyethylene implants, (f) polytetrafluoroethylene implants, and (g) injectable filler materials. 3. Identify the advantages and disadvantages of each of these biomaterials. 4. Understand the specific techniques that may aid in the use these grafts or implants. This review specifically addresses the use of homologous grafts and allogenic implants in rhinoplasty. It is important to stress that autologous materials remain the preferred graft material for use in rhinoplasty, owing to their high biocompatibility and low risk of infection and extrusion. However, concerns of donor-site morbidity, graft availability, and graft resorption have motivated the development and use of homologous and allogenic implants.

  8. Socially disadvantaged parents of children treated with allogeneic haematopoietic stem cell transplantation (HSCT)

    DEFF Research Database (Denmark)

    Larsen, Hanne Bækgaard; Heilmann, Carsten; Johansen, Christoffer

    2013-01-01

    PURPOSE: This study was undertaken to test a daily Family Navigator Nurse (FNN) conducted intervention program, to support parents during the distressful experience of their child's Allogeneic Haematopoietic Stem Cell Transplantation (HSCT). METHODS: A qualitative analysis of the supportive...

  9. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

    Directory of Open Access Journals (Sweden)

    V. Wiegering

    2017-03-01

    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  10. The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras

    International Nuclear Information System (INIS)

    Skidmore, B.J.; Miller, L.S.

    1978-01-01

    A simple, rapid and accurate method was devised for determining lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250-500 μl of blood, 1-7 x 10 5 cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type. (Auth.)

  11. [Human herpesvirus-6 pneumonitis following autologous peripheral blood stem cell transplantation].

    Science.gov (United States)

    Saitoh, Yuu; Gotoh, Moritaka; Yoshizawa, Seiichiro; Akahane, Daigo; Fujimoto, Hiroaki; Ito, Yoshikazu; Ohyashiki, Kazuma

    2018-01-01

    A-46-year-old man was diagnosed with peripheral T cell lymphoma, not otherwise specified. He achieved a complete remission after pirarubicin, cyclophosphamide, vincristine, and prednisolone (THP-COP) therapy and successful autologous peripheral blood stem-cell transplantation (AutoSCT). However, 6 months post AutoSCT, he complained of fever. Chest computed tomography of the patient displayed bilateral interstitial pneumonitis. Human herpesvirus-6 (HHV-6) DNA was detected in his bronchoalveolar lavage fluid. Therefore, the patient was confirmed for HHV-6 pneumonitis. The treatment with foscarnet was effective, and no relapse was noticed in the patient. Besides, we have experienced pneumonitis of unknown origin in some patients after autologous or allogeneic stem-cell transplantations. Moreover, most of the above patients were clinically diagnosed using serum or plasma markers. Therefore, examining respiratory symptoms after AutoSCT would enable a more accurate diagnosis as well as treatment of patients with HHV-6 pneumonitis.

  12. Second myeloablative allogeneic stem cell transplantation (SCT) using cord blood for leukemia relapsed after initial allogeneic SCT.

    Science.gov (United States)

    Konuma, Takaaki; Ooi, Jun; Takahashi, Satoshi; Tomonari, Akira; Tsukada, Nobuhiro; Kato, Seiko; Sato, Aki; Monma, Fumihiko; Kasahara, Senji; Uchimaru, Kaoru; Iseki, Tohru; Tojo, Arinobu; Asano, Shigetaka

    2009-06-01

    There are many reports of second allogeneic stem cell transplantation (allo-SCT) using cord blood (CB) for graft failure after initial allo-SCT. However, the efficacy of second allo-SCT using CB for patients with leukemia relapsed after initial allo-SCT is unknown. We report the results of second allo-SCT using CB in seven adult patients with leukemia relapsed after initial allo-SCT. All patients received a myeloablative conditioning regimen including oral busulfan 16 mg/kg, intravenously fludarabine 100mg/m(2) and cyclophosphamide 120 mg/kg. All but one patient had myeloid reconstitution and four patients remain alive at between 4 and 40 months after second SCT. We conclude that second myeloablative allo-SCT using CB may be feasible in selected patients with the relatively younger age, less organ damage and longer time interval between first and second allo-SCT.

  13. Comparative analysis of autologous blood transfusion and allogeneic blood transfusion in surgical patients

    OpenAIRE

    Long, Miao-Yun; Liu, Zhong-Han; Zhu, Jian-Guang

    2014-01-01

    Objective: To investigate application effects of autologous blood transfusion and allogeneic blood transfusion in surgically treated patients receiving spine surgery, abdomen surgery and ectopic pregnancy surgery. Methods: 130 patients who would undergo selective operations were divided into autologous transfusion group and allogeneic transfusion group. Both groups received the same anesthesia, and there was no significant difference in transfusion volume or fluid infusion volume. Results: Th...

  14. Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model

    OpenAIRE

    Saso, Srdjan; Petts, Gemma; David, Anna L.; Thum, Meen-Yau; Chatterjee, Jayanta; Vicente Antón, José Salvador; Marco Jiménez, Francisco; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priorei, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J. Richard

    2015-01-01

    [EN] Objective: Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. Study desig...

  15. Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-15-1-0234 TITLE: Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion PRINCIPAL...14/2017 4. TITLE AND SUBTITLE Establishment of donor Chimerism Using Allogeneic Bone Marrow with AMP Cell Co-infusion 5a. CONTRACT NUMBER 5b. GRANT...tolerance induction of all types of allografts. In this study, we investigate whether co-infusion of amnion- derived multipotent progenitor (AMP) cells

  16. The Impact of Splenectomy in Myelofibrosis Patients before Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Robin, Marie; Zine, Maryem; Chevret, Sylvie; Meignin, Véronique; Munoz-Bongrand, Nicolas; Moatti, Hannah; Xhaard, Aliénor; Sicre de Fontbrune, Flore; Peffault de Latour, Régis; Sarfati, Emile; Socié, Gérard

    2017-06-01

    Performing a pretransplantation splenectomy in patients with myelofibrosis (MF) is a matter of debate, as while the procedure improves hematological recovery, it may lead to severe morbidities. We retrospectively analyzed data from 85 consecutive patients who underwent transplantation in our center for MF, including 39 patients who underwent splenectomy before their transplantation. A majority of them had primary MF (78%), were considered high-risk patients (84% dynamic international prognostic scoring system intermediate-2 or higher), and had received transplants from HLA-matched sibling donors (56%) after a reduced-intensity conditioning regimen (82%). One-half of all splenectomized patients presented surgical or postsurgical morbidities, most frequently thrombosis and hemorrhage. After adjustment using Cox models, pretransplantation splenectomy was not associated with nonrelapse mortality or post-transplantation relapse but with an improved overall survival (OS) and event-free survival (EFS). We conclude that some patients with huge splenomegaly may undergo pretransplantation splenectomy without a deleterious impact on post-transplantation outcomes. OS and EFS improvement should in confirmed in controlled study. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  17. Peripheral orbit model

    CERN Document Server

    Hara, Yasuo

    1975-01-01

    Peripheral orbit model, in which an incoming hadron is assumed to revolve in a peripheral orbit around a target hadron, is discussed. The non-diffractive parts of two-body reaction amplitudes of hadrons are expressed in terms of the radius, width an absorptivity of the orbit. The radius of the orbit is about 1 fm and the width of the orbit is determined by the range of the interaction between the hadrons. The model reproduces all available experimental data on differential cross-sections and polarizations of $K^{-}p\\to K^{-}p$ and $\\bar K^{\\circ}n$ reactions for all angles successfully. This contribution is not included in the proceedings since it will appear in Progress of Theoretical Physics Vol. 51 (1974) No 2. Any person interested in the subject may apply for reprints to the author.

  18. Expression of antigens coded in murine leukemia viruses on thymocytes of allogeneic donor origin in AKR mice following syngeneic or allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wustrow, T.P.; Good, R.A.

    1985-01-01

    Removal of T-lymphocytes from marrow inoculum with monoclonal antibody plus complement permitted establishment of long-lived allogeneic chimeras between C57BL/6 and AKR/J mice. Development of leukemia was prevented for 15 mo. Protection from leukemia occurred with both young (4 wk) and older (4 mo) recipients. AKR mice reconstituted with syngeneic marrow or control AKR mice all developed leukemia-lymphoma before 1 yr of age. During spontaneous lymphomagenesis in AKR mice, amplified expression of gag or env gene-coded virus antigens on the surface of thymocytes preceded leukemia development and evidence for amplification of other virus genes. These changes generally appeared before 6 mo. Similar viral gene expression and viral gene amplification occurred in the thymus and spleen cells of leukemia-resistant chimeric mice. Using monoclonal antibodies to Mr 70,000 glycoprotein epitopes characteristic of ecotropic, xenotropic, or dualtropic viruses, antigens marking each virus form were found on thymocytes of allogeneic 4-wk and 4-mo chimeras as well as on the cells of AKR mice and of AKR mice reconstituted with syngeneic marrow. Flow cytometric analysis showed amplification of the virus genes in mice protected from leukemia-lymphoma by allogeneic bone marrow transplantation from leukemia-resistant mice. Allogeneic chimeras and syngeneically transplanted mice both showed evidence of accelerated viremia and of recombinant virus formation. The findings suggest that an event essential to leukemogenesis which occurs within the AKR lymphoid cells or their environment is lacking in the allogeneic chimeras. The nature of this influence of a resistance gene or genes introduced into AKR mice by allogeneic bone marrow transplantation deserves further study

  19. Allogeneic transplantation of programmable cells of monocytic origin (PCMO) improves angiogenesis and tissue recovery in critical limb ischemia (CLI): a translational approach.

    Science.gov (United States)

    Berndt, Rouven; Hummitzsch, Lars; Heß, Katharina; Albrecht, Martin; Zitta, Karina; Rusch, Rene; Sarras, Beke; Bayer, Andreas; Cremer, Jochen; Faendrich, Fred; Groß, Justus

    2018-04-27

    Employing growth factor-induced partial reprogramming in vitro, peripheral human blood monocytes can acquire a state of plasticity along with expression of various markers of pluripotency. These so-called programmable cells of monocytic origin (PCMO) hold great promise in regenerative therapies. The aim of this translational study was to explore and exploit the functional properties of PCMO for allogeneic cell transplantation therapy in critical limb ischemia (CLI). Using our previously described differentiation protocol, murine and human monocytes were differentiated into PCMO. We examined paracrine secretion of pro-angiogenic and tissue recovery-associated proteins under hypoxia and induction of angiogenesis by PCMO in vitro. Allogeneic cell transplantation of PCMO was performed in a hind limb ischemia mouse model in comparison to cell transplantation of native monocytes and a placebo group. Moreover, we analyzed retrospectively four healing attempts with PCMO in patients with peripheral artery disease (PAD; Rutherford classification, stage 5 and 6). Statistical analysis was performed by using one-way ANOVA, Tukey's test or the Student's t test, p < 0.05. Cell culture experiments revealed good resilience of PCMO under hypoxia, enhanced paracrine release of pro-angiogenic and tissue recovery-associated proteins and induction of angiogenesis in vitro by PCMO. Animal experiments demonstrated significantly enhanced SO 2 saturation, blood flow, neoangiogenesis and tissue recovery after treatment with PCMO compared to treatment with native monocytes and placebo. Finally, first therapeutic application of PCMO in humans demonstrated increased vascular collaterals and improved wound healing in patients with chronic CLI without exaggerated immune response, malignant processes or extended infection after 12 months. In all patients minor and/or major amputations of the lower extremity could be avoided. In summary, PCMO improve angiogenesis and tissue recovery in chronic

  20. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras

    International Nuclear Information System (INIS)

    Rueedi, E.S.; Sykes, M.; Ildstad, S.T.; Chester, C.H.; Althage, A.; Hengartner, H.; Sachs, D.H.; Zinkernagel, R.M.

    1989-01-01

    Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells

  1. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-01-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection

  2. Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant

    Directory of Open Access Journals (Sweden)

    Karin Kosulin

    2018-02-01

    Full Text Available Human adenoviruses (HAdV are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%, and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p < 0.01. In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p < 0.0001. The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.

  3. Conditioning with Treosulfan and Fludarabine Followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

    Science.gov (United States)

    Nemecek, Eneida R.; Guthrie, Katherine A.; Sorror, Mohamed L.; Wood, Brent L.; Doney, Kristine C.; Hilger, Ralf A.; Scott, Bart L.; Kovacsovics, Tibor J.; Maziarz, Richard T.; Woolfrey, Ann E.; Bedalov, Antonio; Sanders, Jean E.; Pagel, John M.; Sickle, Eileen J.; Witherspoon, Robert; Flowers, Mary E.; Appelbaum, Frederick R.; Deeg, H. Joachim

    2010-01-01

    In this prospective study 60 patients of median age 46 (range 5–60) years, with acute myeloid leukemia (AML; n=44), acute lymphoblastic leukemia (ALL; n=3), or myelodysplastic syndrome (MDS; n=13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine combination. Most patients were considered at high risk for relapse or non-relapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n=5) or 14 g/m2/day (n=55) on days -6 to -4, and fludarabine (30 mg/m2/day) on days -6 to -2, followed by infusion of marrow (n=7) or peripheral blood stem cells (n=53) from HLA-identical siblings (n=30) or unrelated donors (n=30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival for all patients was 58% and 88% for patients without high risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/fludarabine regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/fludarabine to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients. PMID:20685259

  4. Roles of Toll-like receptors in allogeneic islet transplantation.

    Science.gov (United States)

    Ro, Han; Hong, Juho; Kim, Beom Seok; Lee, Eun Won; Kim, Myung-Gyu; Han, Kyu Hyun; Yeom, Hye-Jung; Lee, Eun Mi; Jeong, Jong Cheol; Oh, Kook-Hwan; Ahn, Curie; Yang, Jaeseok

    2012-11-27

    Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation. To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-KO mice. Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-β promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L. TLRs in both donor islets and recipients are involved in islet allograft

  5. Daspsone Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    P A Sarojini

    1988-01-01

    Full Text Available A 24 year old lady being treated with 300 mg of dapsone daily for dermatitits herpetiformis, developed weakness and wasting of muscles of feet with claw hand deformity and t drop, 2 months tater. Neurological examination and nerve conduction studies conformed the presence of a peripheral motor neuropathy. Dapsone was discontinued and the patient was treated with cotrimatoxazole, gluten-free diet and supportive therapy. This satisfactorily controlled the dermatological lesion without adversely affecting the resolution of her neuropthy. Symptomatic improvement reported by the patient was confirmed by EMG and nerve conduction studies.

  6. Peripheral ossifying fibroma

    Directory of Open Access Journals (Sweden)

    Ameet Mani

    2010-01-01

    Full Text Available The peripheral ossifying fibroma (POF is an exophytic gingival mass of fibrous connective tissue covered with a surface epithelium associated with the formation of randomly dispersed foci of a mineralized product consisting of bone, cementum-like tissue, or dystrophic calcifications having a recurrent rate of nearly 20%. It is one of the most common reactive gingival lesions, which have often been called by the generic term "epulis." This case report describes the clinical and histopathological findings of POF, its differential diagnosis, and treatment.

  7. Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

    Science.gov (United States)

    2018-04-23

    Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Biphenotypic Leukemia; Acute Leukemia of Ambiguous Lineage; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome With Excess Blasts-2; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  8. [Allogeneic vascularized transplantation in cases of bone and joint defects].

    Science.gov (United States)

    Hofmann, G O; Kirschner, M H; Gonschorek, O; Bühren, V

    1999-06-01

    This paper presents preliminary results of allogeneic vascularized transplantations of three femoral diaphyses and four total human knee joints. Grafts were harvested from multi-organ-donors and immediately transplanted. Osteosyntheses were performed employing intramedullary nails. Vascular pedicles of the grafts were anastomosed in end-to-side technique. Immunosuppression mainly based on Cyclosporine and Azathioprine. Grafts' perfusion was demonstrated by DSA and Duplex-sonograms, bone metabolism by SPECT-scintigraphy. Five months following transplantation osteotomies demonstrated consolidation in conventional X-rays. Biopsies of the grafted bone revealed intact osteocytes and arthroscopy demonstrated intact synovial, chondral and ligamentous structures. From the technical aspect vascularized transplantation of the femoral diaphyses and total knee joints is feasible. The main problems are of immunologic nature. Transplantations were performed respecting the ABO-compatibility but with a large HLA-mismatch. Acute and chronic rejection crises may damage the grafts. At least in synovial joints live-long immunosuppression of the recipients seems to be unavoidable.

  9. EXPERIENCE OF USING ALLOGENIC BIOIMPLANTS IN LARYNGEAL RESECTION

    Directory of Open Access Journals (Sweden)

    E. N. Novozhilova

    2017-01-01

    Full Text Available Introduction. Currently, a great importance is being attached to improvement of the surgical component of combination treatment of locally advanced laryngeal cancer. New technological capabilities (transoral microsurgery of the larynx and robotic surgery offer great opportunities for early cancer stages. However, in some cases capabilities of endoscopic laser intervention are limited. Therefore, open laryngeal resection is still relevant as it serves as the only type of radical organ preservation treatment for stages Т2–Т3. But major laryngeal resection is associated with a problem of tissue defect closure.The article describes data on the use of biocompatible materials, their advantages and disadvantages. The study objective is to present experience of using a Russian allogenic bioimplant for plastic reconstruction of the opening of the larynx after laryngeal resection.Materials and methods. The authors present their experience of using a Russian bioimplant produced in collaboration with the Samara Tissue Bank of the Research Institute of Experimental Medicine and Biotechnology of the Samara State Medical University. The material was tested in anterolateral laryngeal resection with simultaneous reconstruction in 5 patients with stages Т2–Т3 laryngeal cancer and in a patient with chondrosarcoma.Conclusion. The Russian biocompatible implant served as a reliable, simple, cheap, and effective variant of plastic material for reconstruction of the larynx.

  10. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Yeager, A M; Kanof, M E; Lake, A M; Kramer, S S; Jones, B; Saral, R; Santos, G W

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT.

  11. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    Science.gov (United States)

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  12. Pneumatosis intestinalis in children after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Yeager, A.M.; Kanof, M.E.; Lake, A.M.; Kramer, S.S.; Jones, B.; Saral, R.; Santos, G.W.

    1987-01-01

    Four children, ages 3 to 8 years, developed pneumatosis intestinalis (PI) after allogeneic bone marrow transplantation (BMT) for acute leukemia or severe aplastic anemia. PI was detected at a median of 48 days (range, 10-63 days) after BMT and was associated with abdominal symptoms and clinical signs. All patients had severe systemic and/or highgrade cutaneous acute graft-versus-host disease (AGVHD) at some time after BMT and were receiving corticosteroids at the time of development of PI; however, PI was associated with concomitant severe AGVHD in only one patient. One patient with PI had Hafnia alvei bacteremia and another patient had gastroenteritis due to rotavirus and adenovirus. All patients were treated with supportive care and systemic broad-spectrum antibiotics, and PI resolved 2-16 days after onset. Two patients died with BMT-associated complications unrelated to PI. Multiple factors contribute to the development of PI after BMT, and the prognosis for recovery from PI is good with medical management alone. Overall survival in these patients is dependent on the frequency and severity of other conditions, such as AGVHD and opportunistic infections, after BMT. (orig.)

  13. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ji-Young [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 150-950 (Korea, Republic of); Cha, Eun Suk; Lee, Jee Eun [Department of Radiology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of); Sung, Sun Hee [Department of Pathology, Ewha Womans University School of Medicine, Seoul 158-710 (Korea, Republic of)

    2013-07-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia.

  14. Isolated Post-Transplantation Lymphoproliferative Disease Involving the Breast and Axilla as Peripheral T-cell Lymphoma

    International Nuclear Information System (INIS)

    Hwang, Ji-Young; Cha, Eun Suk; Lee, Jee Eun; Sung, Sun Hee

    2013-01-01

    Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous group of diseases that represent serious complications following immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually associated with Epstein Barr Virus infection. Moreover, to our knowledge, isolated T-cell PTLD involving the breast is extremely rare and this condition has never been reported previously in the literature. Herein, we report a rare case of isolated T-cell PTLD of the breast that occurred after a patient had been treated for allogeneic peripheral blood stem cell transplantation due to acute myeloblastic leukemia

  15. Drug-induced peripheral neuropathy

    DEFF Research Database (Denmark)

    Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

    2014-01-01

    Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

  16. A standardized multidisciplinary approach reduces the use of allogeneic blood products in patients undergoing cardiac surgery.

    Science.gov (United States)

    Van der Linden, P; De Hert, S; Daper, A; Trenchant, A; Jacobs, D; De Boelpaepe, C; Kimbimbi, P; Defrance, P; Simoens, G

    2001-10-01

    Individual and institutional practices remain an independent predictor factor for allogeneic blood transfusion. Application of a standardized multidisciplinary transfusion strategy should reduce the use of allogeneic blood transfusion in major surgical patients. This prospective non randomized observational study evaluated the effects of a standardized multidisciplinary transfusion strategy on allogeneic blood products exposure in patients undergoing non-emergent cardiac surgery. The developed strategy involved a standardized blood conservation program and a multidisciplinary allogeneic blood transfusion policy based mainly on clinical judgement, not only on a specific hemoglobin concentration. Data obtained in a first group including patients operated from September 1997 to August 1998 (Group pre: n=321), when the transfusion strategy was progressively developed, were compared to those obtained in a second group, including patients operated from September 1998 to August 1999 (Group post: n=315) when the transfusion strategy was applied uniformly. Patient populations and surgical procedures were similar. Patients in Group post underwent acute normovolemic hemodilution more frequently, had a higher core temperature at arrival in the intensive care unit and presented lower postoperative blood losses at day one. Three hundred forty units of packed red blood cells were transfused in 33% of the patients in Group pre whereas 161 units were transfused in 18% of the patients in Group post (P <0.001). Pre- and postoperative hemoglobin concentrations, mortality and morbidity were not different among groups. Development of a standardized multidisciplinary transfusion strategy markedly reduced the exposure of cardiac surgery patients to allogeneic blood.

  17. Effects of X-rays and γ-rays on reconstitution of hematopoiesis and immunity after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Pan Bin; Zeng Lingyu; Cheng Hai; Song Guoliang; Jia Lu; Yan Zhiling; Chen Chong; Xu Kailin

    2011-01-01

    Objective: To determine the conditioning regimen suitable for mice allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Twelve BALB/c mice were randomly divided into 2 equal groups to undergo X-ray irradiation by linear accelerator at the dose of 7.0 Gy (pure X-ray group) or 60 Co source irradiation at the dose of 7.0 Gy (pure γ-ray group). Thirty mice were randomly divided into 2 equal groups to undergo X-ray irradiation and then infusion of bone marrow from donor mice via caudal vein (X-ray + transplantation group) or γ-ray and then infusion of bone marrow via caudal vein (γ-ray + transplantation group). 3, 5, 7, 10, 15, 20, and 30 d later peripheral blood samples were collected to calculate the number of white blood cells (WBCs) and detect the chimeric rates of lymphocytes by flow cytometry. 5, 10, and 20 d after irradiation 15 mice were killed with their lung, liver, small intestine, spleen, and femurs taken out to undergo pathological examination. Results: The survival rates during the period 5-15 days of the γ-ray + transplantation group were all significantly higher than those of the X-ray + transplantation group. The pathological changes of organs of the X-ray + transplantation group were all more severe than those of the γ-ray + transplantation group. Since the fifth day after transplantation cells originating from the donor began to appear in the peripheral blood. The chimeric rate of the γ-ray + transplantation group 10 days after transplantation was (95.53± 2.57) %. The chimeric rates 5, 10, and 20 days after transplantation of the γ-ray + transplantation group were all significantly higher than those of the X-ray + transplantation group (t=15.263, 3.256, P<0.05). The WBC count of both irradiation groups decreased to the lowest level 5 d later and began to increase 10 days after transplantation and the WBC counts of the γ-ray + transplantation group 10 and 20 days after transplantation were both significantly higher than

  18. In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation

    Directory of Open Access Journals (Sweden)

    Max eJameson-Lee

    2014-11-01

    Full Text Available Donor T cell mediated graft versus host effects (GVH may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT. Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP present in HLA-matched recipients of SCT donors (GVH direction. The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential.

  19. Peripheral degenerative joint diseases

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2008-03-01

    Full Text Available Osteoarthritis, a degenerative joint disease, is the most commonrheumatic disorder mainly in a geriatric population. Manifestationsare pain, stiffness and functional loss in the affected joint.According to etiology it is classifi ed as primary (or idiopathicand secondary. Some risk factors for disease development aregenetics, race, age, sex, obesity, occupational activities andarticular biomechanics. Pathogenesis is the same for any cause orlocalization, being catabolic alterations, with synthesis, inhibitionand reparing intent of the cartilage matrix. Metalloproteinases andcytokines (IL-1,IL-6,TNF-α actions promote infl ammatory reactionand cartilage degradation. Pain, the most important symptom,does not correlate with radiologic fi ndings. Peripheral osteoarthritisoccurs predominantly in the knee, hip and hand. Diagnosis is basedon clinical features, laboratorial tests and radiological changes.Rheumatological associations’ guidelines for treatment includenon-pharmacologic (education, physiotherapy, assistive devices,and pharmacologic (analgesics, anti-infl ammatory drugs therapyand surgery. Arthroplasty seems to work better than medicines, butshould be used if other treatments have failed.

  20. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions.......A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  1. DAS181 Treatment of Severe Parainfluenza Virus 3 Pneumonia in Allogeneic Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    B. Dhakal

    2016-01-01

    Full Text Available Parainfluenza virus (PIV may cause life-threatening pneumonia in allogeneic hematopoietic stem cell transplant (HSCT recipients. Currently, there are no proven effective therapies. We report the use of inhaled DAS181, a novel sialidase fusion protein, for treatment of PIV type 3 pneumonia in two allogeneic hematopoietic SCT recipients with respiratory failure.

  2. Allogenic sedimentary components of Bear Lake, Utah and Idaho

    Science.gov (United States)

    Rosenbaum, J.G.; Dean, W.E.; Reynolds, R.L.; Reheis, M.C.

    2009-01-01

    Bear Lake is a long-lived lake filling a tectonic depression between the Bear River Range to the west and the Bear River Plateau to the east, and straddling the border between Utah and Idaho. Mineralogy, elemental geochemistry, and magnetic properties provide information about variations in provenance of allogenic lithic material in last-glacial-age, quartz-rich sediment in Bear Lake. Grain-size data from the siliciclastic fraction of late-glacial to Holocene carbonate-rich sediments provide information about variations in lake level. For the quartz-rich lower unit, which was deposited while the Bear River fl owed into and out of the lake, four source areas are recognized on the basis of modern fluvial samples with contrasting properties that reflect differences in bedrock geology and in magnetite content from dust. One of these areas is underlain by hematite-rich Uinta Mountain Group rocks in the headwaters of the Bear River. Although Uinta Mountain Group rocks make up a small fraction of the catchment, hematite-rich material from this area is an important component of the lower unit. This material is interpreted to be glacial fl our. Variations in the input of glacial flour are interpreted as having caused quasi-cyclical variations in mineralogical and elemental concentrations, and in magnetic properties within the lower unit. The carbonate-rich younger unit was deposited under conditions similar to those of the modern lake, with the Bear River largely bypassing the lake. For two cores taken in more than 30 m of water, median grain sizes in this unit range from ???6 ??m to more than 30 ??m, with the coarsest grain sizes associated with beach or shallow-water deposits. Similar grain-size variations are observed as a function of water depth in the modern lake and provide the basis for interpreting the core grain-size data in terms of lake level. Copyright ?? 2009 The Geological Society of America.

  3. Intravenous Tranexamic Acid Decreases Allogeneic Transfusion Requirements in Periacetabular Osteotomy.

    Science.gov (United States)

    Bryan, Andrew J; Sanders, Thomas L; Trousdale, Robert T; Sierra, Rafael J

    2016-01-01

    Bernese (Ganz) periacetabular osteotomy is associated with significant blood loss and the need for perioperative transfusion. Tranexamic acid decreases blood loss and minimizes transfusion rates in total joint arthroplasty. However, no reports have described its use in patients undergoing Bernese periacetabular osteotomy. This study reports the use of intravenous tranexamic acid in these patients. The study included 137 patients (150 hips) who underwent isolated periacetabular osteotomy at a single institution between 2003 and 2014. Of these, 68 patients (75 hips) received intravenous tranexamic acid 1 g at the time of incision and 1 g at the time of closure. A group of 69 patients (75 hips) served as control subjects who underwent periacetabular osteotomy without administration of intravenous tranexamic acid. Thromboembolic disease was defined as deep venous thrombosis or pulmonary embolism occurring within 6 weeks of surgery. Outcomes measured included transfusion requirements, pre- and postoperative hemoglobin values, operative times, and thromboembolic disease rates. Aspirin was used as the thromboembolic prophylactic regimen in 95% of patients. The rate of allogeneic transfusion was 0 in the tranexamic acid group compared with 21% in the control group (P=.0001). No significant difference was found in the autologous cell salvage requirement (.96 vs 1.01; P=.43) or the thromboembolic disease rate between the tranexamic acid group and the control group (2.67% vs 1.33%; P=.31). The use of intravenous tranexamic acid led to a decreased transfusion requirement with no increased risk of thromboembolic disease in this contemporary cohort of patients undergoing periacetabular osteotomy. Copyright 2016, SLACK Incorporated.

  4. Nonspecific suppressor elements in murine allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1979-01-01

    Spleen cells from long-term mouse allogeneic radiation chimeras were tested for their ability to modulate the graft-versus-host (GVH) or plaque-forming cell (PFC) response of normal lymphocytes transplanted in lethally x-irradiated recipients. In vivo GVH proliferation of normal lymphocytes (syngeneic to donor cells of the chimera) against antigens of host-type in which the chimeric state had been established was reduced by chimera cells. Inhibition varied, some chimeras suppressing GVH more than others and a few not suppressing at all. The suppressive effect was abrogated if the chimera cells were treated with anti-THETA; treatment with anti-IgM did not eliminate this activity. When mixtures of normal donor lymphocytes and chimera cells were given to irradiated recipients genetically different from host or donor, reduction of donor cell GVH also occurred. Further, chimera cells reduced the GVH activity of normal host cells in irradiated recipients differing from the host at one H-2 locus and from the donor at minor histocompatibility loci. The modulating effect of spleen cells from chimeras on the PFC response by normal lymphocytes also varied. Six chimeras induced a 25 to 90% suppression, two enhanced the response, and one showed no effect. Where suppression occurred, treatment of chimera cells with anti-THETA most often, but not always, restored PFC production. Our results show that the suppressive action of splenic lymphoid cells by chimeras is highly nonspecific and variable in expression. We suggest that tolerance in chimeras may be mediated by nonspecific suppressor elements leading to unresponsiveness to a variety of antigens including SRBC

  5. A protocol avoiding allogeneic transfusion in joint arthroplasties.

    Science.gov (United States)

    Suh, You-Sung; Nho, Jae-Hwi; Choi, Hyung-Suk; Ha, Yong-Chan; Park, Jong-Seok; Koo, Kyung-Hoi

    2016-09-01

    Arthroplasties of hip and knee are associated with blood loss, which may lead to adverse patient outcome. Performing arthroplasties in Jehovah's Witness patients who do not accept transfusion has been a matter of concern. We developed a protocol, which avoids transfusion in arthroplasties of Jehovah's Witness patients, and evaluated the feasibility and safety of the protocol. The target of preoperative hemoglobin was more than 10 g/dL. When preoperative hemoglobin was lower than 10 g/dL, 4000 U erythropoietin (3 times a week) and 100 mg iron supplement (every day) were administered until the hemoglobin reached 10 g/dL. When the preoperative hemoglobin was higher than 10 g/dL, 4000 U erythropoietin and 100 mg iron supplement were administered once, before operation. During the operation, cell saver was used. Postoperatively, erythropoietin and iron supplements were administered until the hemoglobin reached 10 g/dL, similar to the preoperative protocol. We evaluated the feasibility of our protocol, perioperative complications and hematologic changes. From 2002 to 2014, 186 Witness patients visited our department. In 179 patients (96.2 %), 77 total knee arthroplasties, 69 bipolar hemiarthroplasties and 33 total hip arthroplasties were performed. The mean hemoglobin level was 12.3 g/dL preoperatively, 9.4 g/dL on postoperative day 3 and 10.3 g/dL on postoperative day 7. One patient died immediately after the arthroplasty and the remaining 178 patients survived. Total joint arthroplasty could be done without transfusion using this protocol in most of our patients. The rates of infection and mortality were similar with known infection and mortality rates of arthroplasties. In patients who do not want allogeneic transfusions, our protocol is a safe alternative to perform joint arthroplasties.

  6. Sclerodermatous GVHD after Allogeneic Bone Marrow Transplant: a Review

    Directory of Open Access Journals (Sweden)

    Gagan Raju

    2017-05-01

    Full Text Available Chronic graft versus host disease (cGVHD is the leading cause of non-relapse mortality after allogeneic hematopoietic bone marrow transplantation (HCT for blood malignancy in patients who survive for more than two years. cGVHD can significantly affect quality of life and cause decreased mobility amongst other grave consequences such as end-organ damage, contributing to morbidity and mortality rates for recipients of HCT. Unlike acute GVHD (aGVHD, the chronic variant of graft versus host disease (GVHD has complex immunopathology involving both humoral and cell immunity. It typically affects the integumentary system, though is known to also affect myofascial, mucocutaneous tissues as well as cause end organ damage ultimately resulting in death. Sclerodermatous cGVHD is a type of cGVHD characterized by involvement of the skin, subcutaneous tissue and fascia without evidence of disease in the viscera. Manifestations of this disease are often evocative of autoimmune disease, which is a self-directed inflammatory reaction to the innate and adaptive immune system in various tissues or multiple organ systems. This inflammatory reaction gives rise to autoantibodies as well as B-cell and T-cell mediated direct toxicity which can cause chronic inflammatory changes of tissues ultimately resulting in tissue scarring and end organ dysfunction. We aim to review the literature on this grave disease and elucidate aspects of the immunopathology of chronic sclerodermatous GVHD in hopes that it may lead to revelations inspiring novel therapies after its diagnosis or preventative measures before stem cell transplantation for malignancy.

  7. Allogeneic stem cell transplantation for thalassemia major in India

    Directory of Open Access Journals (Sweden)

    Vikram Mathews

    2017-12-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT is the only currently available curative treatment for thalassemia major. Since it was first done in 1981, several thousand patients have benefited from it and it is now possible to offer this treatment in different parts of the world with good results. With better risk stratification and supportive care, the results of allo-SCT are now very good even in high risk patients who have significant iron overload related organ dysfunction. The improvements have mainly been in the conditioning strategies with less toxic myeloablation and management of the complications of SCT. However, several challenges remain. Transplant related complications still cause significant morbidity and mortality. There is data to show that the results of transplantation as best if done in well transfused and chelated patients <7 years of age. As only a third of the patients will have a matched related donor, there is need for investigating SCT with alternative donors. Experience with SCT for thalassemia major from matched unrelated donors or haplo-identical donors is still limited but needs further exploration. Adequate management needs to be provided post-SCT for all pre-existing complications particularly iron chelation to prevent further organ dysfunction. Systematic follow-up is needed to measure long term outcomes. The biggest challenges in India are the cost of this treatment and access to centres capable of providing this treatment. With greater support from the government, health insurance and philanthropic programs, there has been a rapid increase in the number of SCTs for thalassemia major in India. The number centres providing this treatment are also increasing making this curative treatment more widely available in India.

  8. Allogenic bone grafts used at Central Hospital during June 1995 to July 1998

    International Nuclear Information System (INIS)

    Yolchai Jongjirasiri; Yongyudh Vajaradul

    1999-01-01

    Producing and using allogenic bone graft in Thailand began ten years ago. There are approximately 1,000 cases a year on orthopaedic surgery at Central Hospital. For using allogenic bone graft from the Bangkok Biomaterial Center, 66 cases were operated since June 1995. This was generated by 30 in males, 36 in females and by ages between 12-81 years old. After the operation, 43 cases had bone gap from injuries and 19 cases, fusion of spondylolisthesis and scoliosis were done. Four cases had tumor surgery, and 59 out of 66 cases had good bone union that is 89%. Delayed union happened in 6 cases only. Immune response to allogenic bone graft has not been found yet

  9. Alternative procedures for reducing allogeneic blood transfusion in elective orthopedic surgery.

    Science.gov (United States)

    Kleinert, Kathrin; Theusinger, Oliver M; Nuernberg, Johannes; Werner, Clément M L

    2010-09-01

    Perioperative blood loss is a major problem in elective orthopedic surgery. Allogeneic transfusion is the standard treatment for perioperative blood loss resulting in low postoperative hemoglobin, but it has a number of well-recognized risks, complications, and costs. Alternatives to allogeneic blood transfusion include preoperative autologous donation and intraoperative salvage with postoperative autotransfusion. Orthopedic surgeons are often unaware of the different pre- and intraoperative possibilities of reducing blood loss and leave the management of coagulation and use of blood products completely to the anesthesiologists. The goal of this review is to compare alternatives to allogeneic blood transfusion from an orthopedic and anesthesia point of view focusing on estimated costs and acceptance by both parties.

  10. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation

    International Nuclear Information System (INIS)

    Thomas, E.D.; Buckner, C.D.; Banaji, M.

    1977-01-01

    One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3 to 17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted rejected and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1--4 1 / 2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor

  11. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  12. Peripheral dentinogenic ghost cell tumor

    Directory of Open Access Journals (Sweden)

    Sushant S Kamat

    2013-01-01

    Full Text Available Dentinogenic ghost cell tumors (DGCT are uncommon lesions mainly with rare peripheral types. This report presents a case of peripheral DGCT on the left side of the mandibular alveolar ridge of a heavy smoker, a 68-year-old man, with main presenting feature as a mild pain. Submandibular lymphadenopathy and radiological "saucerization" were evident. Differential diagnosis included fibroma, neurofibroma, peripheral ameloblastoma, peripheral odontogenic fibroma, and peripheral giant cell granuloma. Histologically, ameloblastoma-like epithelial elements were seen in association with grouped ghost cells. Proliferating polyhedral cells and stellate reticulum-like cells with various densities were spread over a wide range of the field. The lesion was curetted and after 2 years of follow up, it did not recur.

  13. Cytomegalovirus pp65 antigenemia-guided pre-emptive treatment with ganciclovir after allogeneic stem transplantation: a single-center experience.

    Science.gov (United States)

    Manteiga, R; Martino, R; Sureda, A; Labeaga, R; Brunet, S; Sierra, J; Rabella, N

    1998-11-01

    The optimal prophylactic strategy for cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation has not yet been established. The aim of this study was to analyze our single-center experience with a uniform protocol of CMV antigenemia-guided pre-emptive treatment with ganciclovir (GCV) after allografting. Fifty-two consecutive adult patients, 48 of them transplanted from HLA-identical matched related donors were included. T cell-depleted marrow or peripheral blood were used in 21 cases. After engraftment, weekly blood samples were tested for CMV pp65 antigenemia and viremia (conventional cultures) until day +100. GCV was started if CMV antigenemia and/or CMV viremia were detected. CMV infection (CMV-I) was found in 19 patients (37%). Seven patients suffered from CMV disease (CMV-D), three colitis and four pneumonias. There was one death directly related to CMV-D and three further cases died from refractory GVHD with CMV-D. Only one patient developed CMV pneumonia without any previous positive antigenemia and/or viremia. Multivariate analysis identified grades II-IV acute GVHD (P = 0.02) and peripheral blood stem cell transplantation (P = 0.03) to be risk factors for developing CMV-I. In conclusion, this monitoring protocol allowed early treatment of CMV-I without progression to CMV-D. Pre-emptive therapy had the additional advantage of avoiding GCV administration in most of our allograft recipients.

  14. Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation.

    Science.gov (United States)

    Cesaro, Simone; Peffault de Latour, Regis; Tridello, Gloria; Pillon, Marta; Carlson, Kristina; Fagioli, Franca; Jouet, Jean-Pierre; Koh, Mickey B C; Panizzolo, Irene Sara; Kyrcz-Krzemien, Slawomira; Maertens, Johan; Rambaldi, Alessandro; Strahm, Brigitte; Blaise, Didier; Maschan, Alexei; Marsh, Judith; Dufour, Carlo

    2015-11-01

    We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17 days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3·5 years, the 5-year overall survival (OS) was 60·7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score ≥80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases. © 2015 John Wiley & Sons Ltd.

  15. Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias

    DEFF Research Database (Denmark)

    Nicolini, Franck Emmanuel; Basak, Grzegorz W; Soverini, Simona

    2011-01-01

    T315I(+) Philadelphia chromosome-positive leukemias are inherently resistant to all licensed tyrosine kinase inhibitors, and therapeutic options remain limited. We report the outcome of allogeneic stem cell transplantation in 64 patients with documented BCR-ABL(T315I) mutations. Median follow......) as unfavorable factors. We conclude that allogeneic stem cell transplantation represents a valuable therapeutic tool for eligible patients with BCR-ABL(T315I) mutation, a tool that may or may not be replaced by third-generation tyrosine kinase inhibitors....

  16. Peripheral Auditory Mechanisms

    CERN Document Server

    Hall, J; Hubbard, A; Neely, S; Tubis, A

    1986-01-01

    How weIl can we model experimental observations of the peripheral auditory system'? What theoretical predictions can we make that might be tested'? It was with these questions in mind that we organized the 1985 Mechanics of Hearing Workshop, to bring together auditory researchers to compare models with experimental observations. Tbe workshop forum was inspired by the very successful 1983 Mechanics of Hearing Workshop in Delft [1]. Boston University was chosen as the site of our meeting because of the Boston area's role as a center for hearing research in this country. We made a special effort at this meeting to attract students from around the world, because without students this field will not progress. Financial support for the workshop was provided in part by grant BNS- 8412878 from the National Science Foundation. Modeling is a traditional strategy in science and plays an important role in the scientific method. Models are the bridge between theory and experiment. Tbey test the assumptions made in experim...

  17. Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

    Science.gov (United States)

    Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

    2017-10-01

    Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

  18. Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

    1982-01-01

    A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

  19. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission

    DEFF Research Database (Denmark)

    Nagler, Arnon; Rocha, Vanderson; Labopin, Myriam

    2013-01-01

    Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with busulfan (Bu) are currently the most common myeloablative regimens used in allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous leukemia (AML). Intravenous (IV) Bu has more predictable...

  20. Allogeneic mesenchymal precursor cells (MPCs): an innovative approach to treating advanced heart failure.

    Science.gov (United States)

    Westerdahl, Daniel E; Chang, David H; Hamilton, Michele A; Nakamura, Mamoo; Henry, Timothy D

    2016-09-01

    Over 37 million people worldwide are living with Heart Failure (HF). Advancements in medical therapy have improved mortality primarily by slowing the progression of left ventricular dysfunction and debilitating symptoms. Ultimately, heart transplantation, durable mechanical circulatory support (MCS), or palliative care are the only options for patients with end-stage HF. Regenerative therapies offer an innovative approach, focused on reversing myocardial dysfunction and restoring healthy myocardial tissue. Initial clinical trials using autologous (self-donated) bone marrow mononuclear cells (BMMCs) demonstrated excellent safety, but only modest efficacy. Challenges with autologous stem cells include reduced quality and efficacy with increased patient age. The use of allogeneic mesenchymal precursor cells (MPCs) offers an "off the shelf" therapy, with consistent potency and less variability than autologous cells. Preclinical and initial clinical trials with allogeneic MPCs have been encouraging, providing the support for a large ongoing Phase III trial-DREAM-HF. We provide a comprehensive review of preclinical and clinical data supporting MPCs as a therapeutic option for HF patients. The current data suggest allogeneic MPCs are a promising therapy for HF patients. The results of DREAM-HF will determine whether allogeneic MPCs can decrease major adverse clinical events (MACE) in advanced HF patients.

  1. On the Feasibility of Utilizing Allogeneic Bone Blocks for Atrophic Maxillary Augmentation

    Directory of Open Access Journals (Sweden)

    Alberto Monje

    2014-01-01

    Full Text Available Purpose. This systematic review was aimed at assessing the feasibility by means of survival rate, histologic analysis, and causes of failure of allogeneic block grafts for augmenting the atrophic maxilla. Material and Methods. A literature search was conducted by one reviewer in several databases. Articles were included in this systematic review if they were human clinical trials in which outcomes of allogeneic bone block grafts were studied by means of survival rate. In addition other factors were extracted in order to assess their influence upon graft failure. Results. Fifteen articles fulfilled the inclusion criteria and subsequently were analyzed in this systematic review. A total of 361 block grafts could be followed 4 to 9 months after the surgery, of which 9 (2.4% failed within 1 month to 2 months after the surgery. Additionally, a weighed mean 4.79 mm (95% CI: 4.51–5.08 horizontal bone gain was computed from 119 grafted sites in 5 studies. Regarding implant cumulative survival rate, the weighed mean was 96.9% (95% CI: 92.8–98.7%, computed from 228 implants over a mean follow-up period of 23.9 months. Histologic analysis showed that allogeneic block grafts behave differently in the early stages of healing when compared to autogenous block grafts. Conclusion. Atrophied maxillary reconstruction with allogeneic bone block grafts represents a reliable option as shown by low block graft failure rate, minimal resorption, and high implant survival rate.

  2. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina; Pontoppidan, Peter; Uhlving, Hilde Hylland

    2017-01-01

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immun...

  3. Novel therapies and their integration into allogeneic stem cell transplant for chronic lymphocytic leukemia.

    Science.gov (United States)

    Jaglowski, Samantha M; Byrd, John C

    2012-01-01

    Over the past decade, numerous advances have been made in elucidating the biology of and improving treatment for chronic lymphocytic leukemia (CLL). These studies have led to identification of select CLL patient groups that generally have short survival dating from time of treatment or initial disease relapse who benefit from more aggressive therapeutic interventions. Allogeneic transplantation represents the only potentially curative option for CLL, but fully ablative regimens applied in the past have been associated with significant morbidity and mortality. Reduced-intensity preparative regimens has made application of allogeneic transplant to CLL patients much more feasible and increased the number of patients proceeding to this modality. Arising from this has been establishment of guidelines where allogeneic stem cell transplantation should be considered in CLL. Introduction of new targeted therapies with less morbidity, which can produce durable remissions has the potential to redefine where transplantation is initiated in CLL. This review briefly summarizes the field of allogeneic stem cell transplant in CLL and the interface of new therapeutics with this modality. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Gastrointestinal toxicity, systemic inflammation, and liver biochemistry in allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between liver toxicity, gastrointestinal toxicity, and levels of immune-r...

  5. Blood management in total hip replacement: an analysis of factors associated with allogenic blood transfusion.

    Science.gov (United States)

    Wong, Samuel; Tang, Howard; de Steiger, Richard

    2015-06-01

    The aim of this study was to audit the blood transfusion practice throughout the Epworth Healthcare Hospitals for patients undergoing primary total hip replacement (THR). We determined if blood-saving techniques were having an impact on the risk of allogenic blood transfusion and which patients were at risk of receiving allogenic blood transfusion. This study uses a retrospective audit of 787 patients who had undergone primary THR surgery at three Melbourne hospitals: Epworth Richmond, Epworth Eastern and Epworth Freemasons in 2010. Patient demographics, transfusion requirements and blood-conserving techniques were recorded. One hundred and eighty (23%) patients received allogenic blood transfusion and 18 (2.3%) patients received autologous blood transfusion. On multivariate analysis, preoperative anaemia (odds ratio (OR) 4.7, P blood transfusion. Use of spinal anaesthetic was found to be associated with lower risk of transfusion (OR 0.6, P = 0.0180) compared with general anaesthetic alone. Cell saver, acute normovolaemic haemodilution and re-infusion drain tube usage did not have a significant impact on reducing the risk of allogenic blood transfusion. Identification of patients at risk of blood transfusion, correction of preoperative anaemia and a restrictive transfusion policy are important factors to consider in effective perioperative blood management. © 2015 Royal Australasian College of Surgeons.

  6. Preoperative Acute Normovolemic Hemodilution for Minimizing Allogeneic Blood Transfusion: A Meta-Analysis.

    Science.gov (United States)

    Zhou, Xuelong; Zhang, Chenjing; Wang, Yin; Yu, Lina; Yan, Min

    2015-12-01

    Previous studies have evaluated the efficacy of preoperative acute normovolemic hemodilution (PANH) in reducing the need for allogeneic blood transfusion. However, the results to date have been controversial. In this study, we sought to reassess the efficacy and safety of PANH based on newly emerging evidence. Medline, EMBASE, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials databases were searched using the key words "hemodilution," "autotransfusion," or "hemorrhage" to retrieve all randomized controlled trials examining the benefits of PANH compared with control patients not undergoing PANH in any type of surgery. Sixty-three studies involving 3819 patients were identified. The risk of requiring an allogeneic blood transfusion and the overall volume of allogeneic red blood cell transfused during the perioperative period were reduced in the PANH group compared with the control group (relative risk, 0.74; 95% confidence interval, 0.63 to 0.88; P = 0.0006; weighted mean difference, -0.94 units; 95% confidence interval, -1.27 to -0.61 units; P transfusion. Perioperative blood loss, adverse events, and the length of hospitalization were comparable between these groups. Although these results suggest that PANH is effective in reducing allogeneic blood transfusion, we identified significant heterogeneity and publication bias, which raises concerns about the true efficacy of PANH.

  7. Unrelated allogeneic stem-cell transplantation in adult patients – 10-year experience

    Directory of Open Access Journals (Sweden)

    Jožef Pretnar

    2012-12-01

    Conclusion: Unrelated allogeneic stem-cell transplantation is suitable for acute myeloblastic leukemias with unfavorable risk factors. However, results in acute lymphoblastic leukemia are worse. Unrelated transplantation is not efficient as salvage treatment for patients with recurrent disease after autologous transplantation or chemotherapy- resistant relapse.

  8. The risks of using allogeneic cell lines for vaccine production : The example of Bovine Neonatal Pancytopenia

    NARCIS (Netherlands)

    Benedictus, Lindert; Bell, Charlotte R

    2017-01-01

    INTRODUCTION: Bovine neonatal pancytopenia (BNP) is a hemorrhagic disease that emerged in calves across Europe in 2007. Its occurrence is attributed to immunization of the calf's mother with a vaccine produced using an allogeneic cell line. Vaccine-induced alloantibodies specific for

  9. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Storb, Rainer; Gyurkocza, Boglarka; Storer, Barry E

    2013-01-01

    We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the pures...

  10. Titanium implant insertion into dog alveolar ridges augmented by allogenic material

    DEFF Research Database (Denmark)

    Pinholt, E M; Haanaes, H R; Donath, K

    1994-01-01

    The purpose of this investigation was to evaluate whether titanium endosseous implants would osseointegrate in dog alveolar ridges augmented by allogenic material. In 8 dogs en bloc resection, including 2 pre-molars, was performed bilaterally in the maxilla and the mandible. After a healing period...

  11. Prolonged Survival of Subcutaneous Allogeneic Islet Graft by Donor Chimerism without Immunosuppressive Treatment

    Directory of Open Access Journals (Sweden)

    Brend Ray-Sea Hsu

    2017-01-01

    Full Text Available The aim of this study was to investigate whether tolerance-induced protection of islets in the renal subcapsular space can also prevent subcutaneous allogeneic islets from being rejected. We used bone marrow stem cells from C57BL/6 (H2b mice to construct donor chimerism in conditioned diabetic BALB/c (H2d mice and investigated the effect of donor chimerism on engraftment and survival of subcutaneously transplanted allogeneic islets in streptozotocin-induced diabetic mice. We also studied the anti-inflammatory effect of mesenchymal stem cell on islet engraftment. Full but not low-grade or no donor chimerism was associated with successful engraftment of allogeneic islets and restoration of normoglycemia in the treated diabetic mice. The temporary hyperglycemia was 11 ± 1 versus 19 ± 5 days (p<0.05 for the mice with full donor chimerism with transplanted islets in the renal subcapsular space versus the subcutaneous space, respectively. Cotransplantation of mesenchymal stem cell did not enhance alloislet engraftment. Full multilineage donor chimerism was associated with a higher transient expansion of CD11b+ and Gr-1+ myeloid progenitor cells and effector memory CD4 and CD8 T cells. In conclusion, full donor chimerism protected both renal subcapsular and subcutaneous allogeneic islets in this rodent transplantation model.

  12. The effect of allogenic versus autologue mesenchymal stem cells in bone reconstructio

    DEFF Research Database (Denmark)

    Jensen, Stefan; Overgaard, Søren; Ding, Ming

    2008-01-01

    with allogenic MSC (group#3) proved to have a significant higher mean SFE (Fisher's LSD-test). The other groups (#1 and #2) had a slightly higher mean SFE (Table 2). Discussion and Conclusion: There are shown two interesting things in this minor pilot-study. There is a trend showing, that the use of MSC has...

  13. Peripheral T-Cell Lymphoma

    Science.gov (United States)

    ... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

  14. Network node for peripheral sharing

    International Nuclear Information System (INIS)

    Bobbitt, J.; Johnson, M.

    1977-01-01

    A module which enables several independent computer systems to share the peripherals (graphics display and line printer) of a PDP-11 computer is described. The module requires no software support in the PDP-11

  15. Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic lymphocytic leukemia.

    Science.gov (United States)

    Nishida, Tetsuya; Hudecek, Michael; Kostic, Ana; Bleakley, Marie; Warren, Edus H; Maloney, David; Storb, Rainer; Riddell, Stanley R

    2009-07-15

    Allogeneic nonmyeloablative hematopoietic stem cell transplant (NM-HSCT) can result in durable remission of chronic lymphocytic leukemia (CLL). It is thought that the efficacy of NM-HSCT is mediated by recognition of tumor cells by T cells in the donor stem cell graft. We evaluated the development of CTLs specific for CLL after NM-HSCT to determine if their presence correlated with antitumor efficacy. Peripheral blood mononuclear cells obtained from 12 transplant recipients at intervals after NM-HSCT were stimulated in vitro with CLL cells. Polyclonal T-cell lines and CD8(+) T-cell clones were derived from these cultures and evaluated for lysis of donor and recipient target cells including CLL. The presence and specificity of responses was correlated with clinical outcomes. Eight of the 12 patients achieved remission or a major antitumor response and all 8 developed CD8(+) and CD4(+) T cells specific for antigens expressed by CLL. A clonal analysis of the CD8(+) T-cell response identified T cells specific for multiple minor histocompatibility (H) antigens expressed on CLL in six of the responding patients. A significant fraction of the CD8(+) T-cell response in some patients was also directed against nonshared tumor-specific antigens. By contrast, CLL-reactive T cells were not detected in the four patients who had persistent CLL after NM-HSCT, despite the development of graft-versus-host disease. The development of a diverse T-cell response specific for minor H and tumor-associated antigens expressed by CLL predicts an effective graft-versus-leukemia response after NM-HSCT.

  16. Next-generation sequencing-based detection of circulating tumour DNA After allogeneic stem cell transplantation for lymphoma.

    Science.gov (United States)

    Herrera, Alex F; Kim, Haesook T; Kong, Katherine A; Faham, Malek; Sun, Heather; Sohani, Aliyah R; Alyea, Edwin P; Carlton, Victoria E; Chen, Yi-Bin; Cutler, Corey S; Ho, Vincent T; Koreth, John; Kotwaliwale, Chitra; Nikiforow, Sarah; Ritz, Jerome; Rodig, Scott J; Soiffer, Robert J; Antin, Joseph H; Armand, Philippe

    2016-12-01

    Next-generation sequencing (NGS)-based circulating tumour DNA (ctDNA) detection is a promising monitoring tool for lymphoid malignancies. We evaluated whether the presence of ctDNA was associated with outcome after allogeneic haematopoietic stem cell transplantation (HSCT) in lymphoma patients. We studied 88 patients drawn from a phase 3 clinical trial of reduced-intensity conditioning HSCT in lymphoma. Conventional restaging and collection of peripheral blood samples occurred at pre-specified time points before and after HSCT and were assayed for ctDNA by sequencing of the immunoglobulin or T-cell receptor genes. Tumour clonotypes were identified in 87% of patients with adequate tumour samples. Sixteen of 19 (84%) patients with disease progression after HSCT had detectable ctDNA prior to progression at a median of 3·7 months prior to relapse/progression. Patients with detectable ctDNA 3 months after HSCT had inferior progression-free survival (PFS) (2-year PFS 58% vs. 84% in ctDNA-negative patients, P = 0·033). In multivariate models, detectable ctDNA was associated with increased risk of progression/death (Hazard ratio 3·9, P = 0·003) and increased risk of relapse/progression (Hazard ratio 10·8, P = 0·0006). Detectable ctDNA is associated with an increased risk of relapse/progression, but further validation studies are necessary to confirm these findings and determine the clinical utility of NGS-based minimal residual disease monitoring in lymphoma patients after HSCT. © 2016 John Wiley & Sons Ltd.

  17. Predictors for successful PBSC collection on the fourth day of G-CSF-induced mobilization in allogeneic stem cell donors.

    Science.gov (United States)

    van Oostrum, Anja; Zwaginga, Jaap Jan; Croockewit, Sandra; Overdevest, Jacqueline; Fechter, Mirjam; Ruiterkamp, Bart; Brand, Anneke; Netelenbos, Tanja

    2017-12-01

    Peripheral blood stem cells (PBSCs) used for allogeneic transplantation are collected by apheresis after pre-treatment of donors with G-CSF. Using modern apheresis devices stem cells can be collected more efficiently. It was studied whether collection on the 4th instead of the 5th day after initiation of G-CSF treatment might be feasible. Stem cell yields that could have been collected on day 4 were calculated in two cohorts treated with 10 µg/kg G-CSF once daily (n = 106, cohort I) or 5 µg/kg twice daily schedule (n = 85, cohort II). Harvests were predicted using the median collection efficiency (CE) of the apheresis machine and regarded successful when > 5.0 x10 6 CD34 +/ kg recipient body weight. Successful harvests at day 4 could have been obtained in only 22.6% and 41.2% of donors in cohort I and II respectively, while the expected successful collections on day 5 were 55.7% and 76.5%. Individual donor factors that correlated with a successful harvest on day 4 were weight, BMI, age, ratio donor/recipient weight and total G-CSF dose in cohort I, whereas ratio donor/recipient weight was the only significant predictor in cohort II. Donor weight, BMI and total G-CSF dose correlated positively with CD34 + values in the blood on day 4 in all donors. However, donor characteristics were not able to be used as strong predictors in daily practice. In conclusion, PBSC collection on day 4 will not result in a successful harvest in most stem cell donors, however using a twice daily G-CSF scheme increases the yield. © 2017 Wiley Periodicals, Inc.

  18. The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells.

    Science.gov (United States)

    McGregor, D K; Keever-Taylor, C A; Bredeson, C; Schur, B; Vesole, D H; Logan, B; Chang, C-C

    2005-06-01

    We performed real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood (PB) and/or bone marrow (BM) samples collected pre- and post transplant from 23 recipient-donor pairs receiving allogeneic stem cell transplantation (allo-SCT) for follicular lymphoma (FL). Of 23 donors, 11 had a PB and/or BM sample positive for t(14;18) (BCL2/IGH fusion) at low levels (donors with (n=11) and those without (n=12) detectable t(14:18) cells were similar in age, sex, and disease status pretransplant. No differences in the incidence of graft-versus-host-disease (GVHD), delayed engraftment, relapse rate, disease-free survival and overall survival were identified between the groups. Two recipients without detectable t(14;18) cells pre-transplant showed detectable t(14;18) cells at 2 and 11 years after receiving grafts from donors with t(14:18) cells. Neither patient developed FL 1.5 and 2 years after the emergence of t(14;18) cells. Although the sample size is relatively small, our findings suggest that individuals carrying t(14;18) cells may not be excluded as donors given the lack of an association of t(14;18) detected in donors with adverse clinical outcome. It may be necessary to screen for the donor's t(14;18) status before using t(14;18) for monitoring minimal residual disease by RQ-PCR to exclude the possibility of confounding donor's t(14;18) clone.

  19. Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

    Science.gov (United States)

    Carless, Paul A; Rubens, Fraser D; Anthony, Danielle M; O'Connell, Dianne; Henry, David A

    2011-03-16

    Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials

  20. Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits

    Directory of Open Access Journals (Sweden)

    P. Gál

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation. The results were compared with the data for the control defects (without stem cell implantation in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm. Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °. On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °. For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study

  1. Development of a modified prognostic index for patients with aggressive adult T-cell leukemia-lymphoma aged 70 years or younger: possible risk-adapted management strategies including allogeneic transplantation.

    Science.gov (United States)

    Fuji, Shigeo; Yamaguchi, Takuhiro; Inoue, Yoshitaka; Utsunomiya, Atae; Moriuchi, Yukiyoshi; Uchimaru, Kaoru; Owatari, Satsuki; Miyagi, Takashi; Taguchi, Jun; Choi, Ilseung; Otsuka, Eiichi; Nakachi, Sawako; Yamamoto, Hisashi; Kurosawa, Saiko; Tobinai, Kensei; Fukuda, Takahiro

    2017-07-01

    Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy. Copyright© 2017 Ferrata Storti Foundation.

  2. Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model.

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    Saso, Srdjan; Petts, Gemma; David, Anna L; Thum, Meen-Yau; Chatterjee, Jayanta; Vicente, Jose S; Marco-Jimenez, Francisco; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priore, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J Richard

    2015-02-01

    Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility (AUFI). The goal of UTx remains achieving pregnancy and live birth of a healthy neonate following allogeneic UTx. Our aim was to assess whether fertility was possible following allogeneic uterine transplantation (UTx), when the recipient had demonstrated long-term survival and had been administered immunosuppression. Nine allogeneic UTx in New Zealand White rabbits were performed using a pre-determined protocol. Tacrolimus was the immunosuppressant selected. Embryos were transferred into both cornua of the sole living recipient via a mini-midline laparotomy. The pregnancy was monitored with regular reproductive profiles and serial trans-abdominal ultrasound to measure conceptus growth (gestation sac and crown rump length (CRL)). In the sole surviving doe a gestation sac was visualised on ultrasound from Day 9 (D9) after embryo transfer. Gestation sac diameter and CRL increased from D9 to D16 but by D18 the gestation sac had reduced in size. The fetus was no longer visible, suggesting fetal resorption had occurred. Subsequent scans on D22 and D25 did not demonstrate a gestation sac. Scheduled necropsy on D27 and histopathology confirmed evidence of a gravid uterus and presence of a gestational sac. A single episode of acute rejection occurred on D13. Pregnancy was achieved after rabbit allogeneic UTx but serial ultrasound suggested that fetal demise occurred prior to scheduled necropsy. The study represents only the third example of conception and pregnancy following an animal allogeneic UTx. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience

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    Mira Romany Massoud

    Full Text Available ABSTRACT Introduction: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. Methods: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. Results: Forty-one patients were reviewed: 10 (24% had Hodgkin's and 31 (76% had non-Hodgkin lymphomas. The median age was 50 years and 23 (56% were male. The majority of patients (68% had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43% patients were in complete and seven (17% were in partial remission. Most (95% patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. Conclusions: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

  4. Effect of allogenic thymic cells on radioleukaemogenesis in AKR-T1ALD mice

    International Nuclear Information System (INIS)

    Legrand, E.; Sankar-Mistry, P.; Kressmann, M.C.

    1975-01-01

    When AKR mice are irradiated with a sub-lethal dose (4 times 175 R), thymic lymphosarcomas (L.S.) occur earlier than in controls. This accelerated leukaemogenesis is not inhibited by syngenic restoration with bone marrows cells (BM). Using the AKR/T1ALD substrain which bears 38 chromosomes with 1 metacentric markers, it has been shown that AKR radio-chimaeras restored by T1ALD BM developed two kinds of L.S.: early (radiation-induced) L.S. originating mainly from host cells surviving irradiation and late L.S. from donor cells. The experiments were to investigate the potential influence of normal allogenic thymic cells, with or without syngenic B.M., on the incidence, latency and origin of LS appearing in irradiated AKR recipients. Adding C3H allogenic thymic cells to syngenic B.M. increases the percentage of early L.S. whose latencies are unchanged. Besides, when C3H thymic cells are injected to irradiated controls without syngenic B.M. cells, L.S. are seen to occur significantly earlier than in just the irradiated animals alone. In radio-chimaeras restored by allogenic thymic cells and syngenic B.M., except in one case, all the L.S. were seen to originate from B.M. cells. The interpretation of these results depends on the possible role of allogenic thymic cells on host cells surviving the irradiation, or the exogeneous B.M. In the first case, allogenic thymocytes could induce a graft versus host reaction increasing the post-irradiation depletion of lymphoid system and hastening thymic endoregeneration which is supposed to be the first step towards leukaemogenesis. The second hypothesis, which seems the most likely, would be that C1H thymic cells could selectively act on host cells surviving irradiation and enhance the differenciation of haemopoietic precursors at the expense of the lymphoid cells [fr

  5. Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

    Science.gov (United States)

    Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

    2018-02-15

    Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Recipient dendritic cells, but not B cells, are required antigen-presenting cells for peripheral alloreactive CD8+ T-cell tolerance.

    Science.gov (United States)

    Mollov, J L; Lucas, C L; Haspot, F; Gaspar, J Kurtz C; Guzman, A; Sykes, M

    2010-03-01

    Induction of mixed allogeneic chimerism is a promising approach for achieving donor-specific tolerance, thereby obviating the need for life-long immunosuppression for solid organ allograft acceptance. In mice receiving a low dose (3Gy) of total body irradiation, allogeneic bone marrow transplantation combined with anti-CD154 tolerizes peripheral CD4 and CD8 T cells, allowing achievement of mixed chimerism with specific tolerance to donor. With this approach, peripheral CD8 T-cell tolerance requires recipient MHC class II, CD4 T cells, B cells and DCs. Recipient-type B cells from chimeras that were tolerant to donor still promoted CD8 T-cell tolerance, but their role could not be replaced by donor-type B cells. Using recipients whose B cells or DCs specifically lack MHC class I and/or class II or lack CD80 and CD86, we demonstrate that dendritic cells (DCs) must express CD80/86 and either MHC class I or class II to promote CD8 tolerance. In contrast, B cells, though required, did not need to express MHC class I or class II or CD80/86 to promote CD8 tolerance. Moreover, recipient IDO and IL-10 were not required. Thus, antigen presentation by recipient DCs and not by B cells is critical for peripheral alloreactive CD8 T cell tolerance.

  7. Bronchiolitis obliterans after allogenic bone marrow transplantation: HRCT findings

    International Nuclear Information System (INIS)

    Jung, Jung Im; Jung, Won Sang; Hahn, Seong Tai; Park, Seog Hee; Min, Chang Ki; Kim, Chun Choo

    2004-01-01

    To evaluate the high resolution computed tomography (HRCT) findings of bronchiolitis obliterans (BO) after bone marrow transplantation (BMT). During the past three years, 11 patients were diagnosed as having BO after BMT when they developed irreversible air flow obstruction, with an FEV 1 value of less than 80% of the baseline value, without any clinical evidence of infection. All 11 patients underwent HRCT, of whom eight also underwent follow-up HRCT. The HRCT images were assessed retrospectively for the presence of decreased lung attenuation, segmental or subsegmental bronchial dilatation, diminution of peripheral vascularity, centrilobular nodules, and branching linear structure on the inspiratory images. The lobar distribution of the decreased lung attenuation and bronchial dilatation was also examined. The presence of air trapping was investigated on the expiratory images. The interval changes of the HRCT findings were evaluated in those patients who had follow-up images. Abnormal HRCT findings were present in all cases; the most common abnormalities were decreased lung attenuation (n=11), subsegmental bronchial dilatation (n=6), diminution of peripheral vascularity (n=6), centrilobular nodules or branching linear structure (n=3), and segmental bronchial dilatation (n=3). Expiratory air trapping was noted in all patients. The decreased lung attenuation and bronchial dilatations were more frequent or extensive in the lower lobes. Interval changes were found in all patients with follow-up HRCT: increased extent of decreased lung attenuation (n=7); newly developed or progressed bronchial dilatation (n=4); and increased lung volume (n=3). HRCT scans are abnormal in patients with BO, with the most commonly observed finding being areas of decreased lung attenuation. While the HRCT findings are not specific, it is believed that their common features can assist in the diagnosis of BO in BMT recipients

  8. HLA-C incompatibilities in allogeneic unrelated hematopoietic stem cell transplantation

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    Jean-Marie eTIERCY

    2014-05-01

    Full Text Available An increasingly larger fraction of patients with hematological diseases are treated by hematopoietic stem cells transplantation (HSCT from HLA matched unrelated donors. Polymorphism of HLA genes represent a major barrier to HSCT because HLA-A,B,C and DRB1 incompatibilities confer a higher risk of aGVHD and mortality. Although >22 million volunteer HLA-typed donors are available worldwide, still a significant number of patients do not find a highly matched HSC donor. Because of the large haplotypic diversity in HLA-B-C associations, incompatibilities occur most frequently at HLA-C, so that unrelated donors with a single HLA-C mismatch often represent the only possible choice. The ratio of HLA-C-mismatched HSCT over the total number of transplants varies from 15-30%, as determined in 12 multicenter studies. Six multicenter studies involving >1800 patients have reported a 21-43% increase in mortality risk. By using in vitro cellular assays a large heterogeneity in T-cell allorecognition has been observed. Yet the permissiveness of individual HLA-C mismatches remains poorly defined. It could be linked to the position and nature of the mismatched residues on HLA-C molecules, but also to variability in the expression levels of the mismatched alleles. The permissive C*03:03-03:04 mismatch is caracterized by full compatibility at residues 9, 97, 99, 116, 152, 156 and 163 reported to be key positions influencing T-cell allorecognition. With a single difference in these key residues the C*07:01-07:02 mismatch might also be considered by analogy as permissive. High variability of HLA-C expression as determined by quantitative RT-PCR has been observed within individual allotypes and shows some correlation with A-B-C-DRB1 haplotypes. Thus in addition to the position of mismatched amino acid residues, expression level of patient’s mismatched HLA-C allotype might influence T-cell allorecognition, with patient's low expression-C alleles representing possible

  9. The Fourth Nagoya International Blood and Marrow Transplantation Symposium: new horizons in allogeneic hematopoietic cell transplantation--2001 revolution.

    Science.gov (United States)

    Sao, Hiroshi; Morishita, Yoshihisa

    2002-02-01

    In this symposium, we saw new horizons in allogeneic transplantation. Are these truly revolutionary? We do not yet know the answer. However, there is no question about the importance of allogeneic T cells. T cells are much more powerful than any pharmacological drug man has ever generated. The question is, how do we take the most advantage of their potential. Every participant was encouraged to search for good answers to this question until the next meeting.

  10. Peripheral nerve conduits: technology update

    Science.gov (United States)

    Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

    2014-01-01

    Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

  11. Comparison of autogeneic and allogeneic natural killer cells immunotherapy on the clinical outcome of recurrent breast cancer

    Directory of Open Access Journals (Sweden)

    Liang S

    2017-08-01

    Full Text Available Shuzhen Liang,1,2 Kecheng Xu,1,2 Lizhi Niu,1,2 Xiaohua Wang,1 Yingqing Liang,1 Mingjie Zhang,3 Jibing Chen,1,2 Mao Lin1,2 1Department of Central Laboratory, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, Guangdong, China; 2Fuda Cancer Institute, Guangzhou, Guangdong, China; 3Hank Bioengineering Co., Ltd, Shenzhen, China Abstract: In the present study, we aimed to compare the clinical outcome of autogeneic and allogeneic natural killer (NK cells immunotherapy for the treatment of recurrent breast cancer. Between July 2016 and February 2017, 36 patients who met the enrollment criteria were randomly assigned to two groups: autogeneic NK cells immunotherapy group (group I, n=18 and allogeneic NK cells immunotherapy group (group II, n=18. The clinical efficacy, quality of life, immune function, circulating tumor cell (CTC level, and other related indicators were evaluated. We found that allogeneic NK cells immunotherapy has better clinical efficacy than autogeneic therapy. Moreover, allogeneic NK cells therapy improves the quality of life, reduces the number of CTCs, reduces carcinoembryonic antigen and cancer antigen 15-3 (CA15-3 expression, and significantly enhances immune function. To our knowledge, this is the first clinical trial to compare the clinical outcome of autogeneic and allogeneic NK cells immunotherapy for recurrent breast cancer. Keywords: clinical outcome, autogeneic, allogeneic, natural killer cells, recurrent breast cancer

  12. Peripheral Atherectomy: Applications and Techniques.

    Science.gov (United States)

    Mittleider, Derek; Russell, Erich

    2016-06-01

    Peripheral atherectomy is a class of procedures that is rapidly increasing in volume. Multiple classes of devices exist, and newer variants are added to the market annually. The devices see wide application for de novo lesions, in-stent restenosis, and adjunctive therapy for drug-coated balloons. The body of evidence supporting atherectomy is less robust than for many other peripheral therapies. The frequency and severity of complications from atherectomy can be significant compared with angioplasty and stenting, and familiarity with preventative and bailout techniques is essential for the interventionalist. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Atherectomy for peripheral arterial disease].

    Science.gov (United States)

    Londero, Louise Skovgaard; Høgh, Annette Langager; Lindholt, Jes Sanddal

    2015-04-13

    Symptomatic peripheral arterial disease is managed according to national and international guidelines and the number of vascular reconstructions performed each year has increased over the past decade mainly due to an increasing frequency of endovascular procedures. Atherectomy as an alternative to the established treatment of symptomatic peripheral arterial disease has recently been analysed in a Cochrane review. In Denmark, atherectomy is not performed and so far the evidence is poor as the method is not an alternative to the established treatment in this country.

  14. Imaging of the peripheral retina

    Directory of Open Access Journals (Sweden)

    Marcus Kernt

    2013-01-01

    Full Text Available The technical progress of the recent years has revolutionized imaging in ophthalmology. Scanning laser ophthalmoscopy (SLO, digital angiography, optical coherence tomography (OCT, and detection of fundus autofluorescence (FAF have fundamentally changed our understanding of numerous retinal and choroidal diseases. Besides the tremendous advances in macular diagnostics, there is more and more evidence that central pathologies are often directly linked to changes in the peripheral retina. This review provides a brief overview on current posterior segment imaging techniques with a special focus on the peripheral retina.

  15. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion

    Science.gov (United States)

    Henry, David A; Carless, Paul A; Moxey, Annette J; O’Connell, Dianne; Stokes, Barrie J; Fergusson, Dean A; Ker, Katharine

    2014-01-01

    a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). Authors’ conclusions Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects. PMID:21412876

  16. Nonmyeloablative and reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation: a clinical review.

    Science.gov (United States)

    Pollack, Seth M; O'Connor, Thomas P; Hashash, Jana; Tabbara, Imad A

    2009-12-01

    Allogeneic hematopoietic stem cell transplantation provides many patients, with hematological and malignant diseases, hope of remission and in some cases cure. Because the toxicities of this approach are severe, its use has been limited to younger healthier patients. Nonmyeloablative and reduced intensity conditioning regimens depend more on donor cellular immune effects and less on the cytotoxic effects of the conditioning regimen to eradicate the underlying disease. This approach is based on the induction of host tolerance to donor cells followed by the administration of scheduled donor T-lymphocytes infusions. Accumulated clinical data have been encouraging, and prospective studies are underway to compare this approach to conventional myeloablative allogeneic stem cell transplantation with regard to outcome, durability of responses, effects on the immune system, and the consequences of late complications such as chronic graft-versus-host disease.

  17. Fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Mori, T; Nakamura, Y; Kato, J; Sugita, K; Murata, M; Kamei, K; Okamoto, S

    2012-02-01

    Rhodotorula species have been increasingly recognized as emerging pathogens, particularly in immunocompromised patients. We herein report on a patient with myelodysplastic syndrome who developed fungemia due to Rhodotorula mucilaginosa after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. He developed severe acute graft-versus-host disease requiring high-dose steroids, and had serially been administered fluconazole and micafungin for the prophylaxis of fungal infection. Although several cases of Rhodotorula infection after HSCT have been reported, all of them were recipients of autologous HSCT, not allogeneic HSCT. A review of all the reported cases of Rhodotorula infection after HSCT revealed that all patients had received fluconazole or echinocandins before the onset of infection. The findings suggest that Rhodotorula species could be causative yeasts, particularly in patients receiving fluconazole or echinocandins, both of which are inactive against the species. © 2011 John Wiley & Sons A/S.

  18. Immune responses to an encapsulated allogeneic islet β-cell line in diabetic NOD mice

    International Nuclear Information System (INIS)

    Black, Sasha P.; Constantinidis, Ioannis; Cui, Hong; Tucker-Burden, Carol; Weber, Collin J.; Safley, Susan A.

    2006-01-01

    Our goal is to develop effective islet grafts for treating type 1 diabetes. Since human islets are scarce, we evaluated the efficacy of a microencapsulated insulin-secreting conditionally transformed allogeneic β-cell line (βTC-tet) in non-obese diabetic mice treated with tetracycline to inhibit cell growth. Relatively low serum levels of tetracycline controlled proliferation of βTC-tet cells without inhibiting effective control of hyperglycemia in recipients. There was no significant host cellular reaction to the allografts or host cell adherence to microcapsules, and host cytokine levels were similar to those of sham-operated controls. We conclude that encapsulated allogeneic β-cell lines may be clinically relevant, because they effectively restore euglycemia and do not elicit a strong cellular immune response following transplantation. To our knowledge, this is First extensive characterization of the kinetics of host cellular and cytokine responses to an encapsulated islet cell line in an animal model of type 1 diabetes

  19. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary...... damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had...... to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation....

  20. Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

    International Nuclear Information System (INIS)

    Brinch, L.; Evensen, S.A.; Albrechtsen, D.; Egeland, T.; Solheim, B.G.; Rollag, H.; Naalsund, A.; Jacobsen, A.B.

    1991-01-01

    The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

  1. Long-term survival of transplanted allogeneic cells engineered to express a T cell chemorepellent.

    Science.gov (United States)

    Papeta, Natalia; Chen, Tao; Vianello, Fabrizio; Gererty, Lyle; Malik, Ashish; Mok, Ying-Ting; Tharp, William G; Bagley, Jessamyn; Zhao, Guiling; Stevceva, Liljana; Yoon, Victor; Sykes, Megan; Sachs, David; Iacomini, John; Poznansky, Mark C

    2007-01-27

    Alloantigen specific T cells have been shown to be required for allograft rejection. The chemokine, stromal cell derived factor-1 (SDF-1) at high concentration, has been shown to act as a T-cell chemorepellent and abrogate T-cell infiltration into a site of antigen challenge in vivo via a mechanism termed fugetaxis or chemorepulsion. We postulated that this mechanism could be exploited therapeutically and that allogeneic cells engineered to express a chemorepellent protein would not be rejected. Allogeneic murine insulinoma beta-TC3 cells and primary islets from BALB/C mice were engineered to constitutively secrete differential levels of SDF-1 and transplanted into allogeneic diabetic C57BL/6 mice. Rejection was defined as the permanent return of hyperglycemia and was correlated with the level of T-cell infiltration. The migratory response of T-cells to SDF-1 was also analyzed by transwell migration assay and time-lapse videomicroscopy. The cytotoxicity of cytotoxic T cell (CTLs) against beta-TC3 cells expressing high levels of SDF-1 was measured in standard and modified chromium-release assays in order to determine the effect of CTL migration on killing efficacy. Control animals rejected allogeneic cells and remained diabetic. In contrast, high level SDF-1 production by transplanted cells resulted in increased survival of the allograft and a significant reduction in blood glucose levels and T-cell infiltration into the transplanted tissue. This is the first demonstration of a novel approach that exploits T-cell chemorepulsion to induce site specific immune isolation and thereby overcomes allograft rejection without the use of systemic immunosuppression.

  2. Activated allogeneic NK cells preferentially kill poor prognosis B-cell chronic lymphocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Diego Sanchez-Martinez

    2016-10-01

    Full Text Available Mutational status of TP53 together with expression of wild type (wt IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL patients. Adoptive cell therapy using allogeneic HLA mismatched Natural Killer (NK cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs the most effective stimulus to activate NK cells. Here we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell activating receptors (NKG2D and NCRs and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.□

  3. Activated Allogeneic NK Cells Preferentially Kill Poor Prognosis B-Cell Chronic Lymphocytic Leukemia Cells.

    Science.gov (United States)

    Sánchez-Martínez, Diego; Lanuza, Pilar M; Gómez, Natalia; Muntasell, Aura; Cisneros, Elisa; Moraru, Manuela; Azaceta, Gemma; Anel, Alberto; Martínez-Lostao, Luis; Villalba, Martin; Palomera, Luis; Vilches, Carlos; García Marco, José A; Pardo, Julián

    2016-01-01

    Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery. This effect depends on the activation protocol, being B-lymphoblastoid cell lines (LCLs) the most effective stimulus to activate NK cells. Here, we have further analyzed the molecular determinants involved in allogeneic NK cell recognition and elimination of B-CLL cells, including the expression of ligands of the main NK cell-activating receptors (NKG2D and NCRs) and HLA mismatch. We present preliminary data suggesting that B-CLL susceptibility significantly correlates with HLA mismatch between NK cell donor and B-CLL patient. Moreover, we show that the sensitivity of B-CLL cells to NK cells depends on the prognosis based on TP53 and IGHV mutational status. Cells from patients with worse prognosis (mutated TP53 and wt IGHV ) are the most susceptible to activated NK cells. Hence, B-CLL prognosis may predict the efficacy of allogenic activated NK cells, and, thus, NK cell transfer represents a good alternative to treat poor prognosis B-CLL patients who present a very short life expectancy due to lack of effective treatments.

  4. A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells.

    Directory of Open Access Journals (Sweden)

    Caroline Aspord

    Full Text Available BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+ CD8 T cells. The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

  5. Informed consent: cultural and religious issues associated with the use of allogeneic and xenogeneic mesh products.

    Science.gov (United States)

    Jenkins, Eric D; Yip, Michael; Melman, Lora; Frisella, Margaret M; Matthews, Brent D

    2010-04-01

    Our aim was to investigate the views of major religions and cultural groups regarding the use of allogeneic and xenogeneic mesh for soft tissue repair. We contacted representatives from Judaism, Islam, Buddhism, Hinduism, Scientology, and Christianity (Baptists, Methodists, Seventh-Day Adventists, Catholics, Lutherans, Church of Jesus Christ of Latter-Day Saints, Evangelical, and Jehovah's Witnesses). We also contacted American Vegan and People for the Ethical Treatment of Animals (PETA). Standardized questionnaires were distributed to the religious and cultural authorities. Questions solicited views on the consumption of beef and pork products and the acceptability of human-, bovine-, or porcine-derived acellular grafts. Dietary restrictions among Jews and Muslims do not translate to tissue implantation restriction. Approximately 50% of Seventh-day Adventists and 40% of Buddhists practice vegetarianism, which may translate into a refusal of the use of xenogeneic tissue. Some Hindus categorically prohibit the use of human tissue and animal products; others allow the donation and receipt of human organs and tissues. PETA is opposed to all uses of animals, but not to human acellular grafts or organ transplantation. Some vegans prefer allogeneic to xenogeneic tissue. Allogeneic and xenogeneic acellular grafts are acceptable among Scientologists, Baptists, Lutherans, Evangelicals, and Catholics. Methodists, Jehovah's Witnesses, and The Church of Jesus Christ of Latter-Day Saints leave the decision up to the individual. Knowledge of religious and cultural preferences regarding biologic mesh assists the surgeon in obtaining a culturally sensitive informed consent for procedures involving acellular allogeneic or xenogeneic grafts. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Aerobic exercise capacity at long-term follow-up after paediatric allogeneic haematopoietic SCT

    DEFF Research Database (Denmark)

    Mathiesen, S; Uhlving, H H; Buchvald, F

    2014-01-01

    Peak oxygen uptake (VO2peak), a measure of aerobic exercise capacity, predicts mortality and morbidity in healthy and diseased individuals. Our aim was to determine VO2peak years after paediatric allogeneic haematopoietic SCT (HSCT) and to identify associations with baseline patient and donor...... type or GvHD were found. Although causes for reduced VO2peak may be multiple, our findings stress the need to focus on physical activity post HSCT to prevent lifestyle diseases and improve quality of life....

  7. Clinical and Surgical Strategies for Avoiding or Reducing Allogeneic Blood Transfusions

    OpenAIRE

    dos Santos, Antonio Alceu; Baumgratz, Jose Francisco; Vila, Jose Henrique Andrade; Castro, Rodrigo Moreira; Bezerra, Rodrigo Freire

    2016-01-01

    Blood transfusions have still been used as a standard therapy to treat severe anemia. Current evidences point to both excessive allogeneic blood consumption and decreased donations, which result in reduced stocks in blood banks. Several studies have increasingly suggested a more restrictive transfusion practice for blood products. Currently, a number of autologous blood conservation protocols in surgeries have been noted. We report a case of severe anemia with 2.9 g/dL hemoglobin, which was s...

  8. Peripheral facial weakness (Bell's palsy).

    Science.gov (United States)

    Basić-Kes, Vanja; Dobrota, Vesna Dermanović; Cesarik, Marijan; Matovina, Lucija Zadro; Madzar, Zrinko; Zavoreo, Iris; Demarin, Vida

    2013-06-01

    Peripheral facial weakness is a facial nerve damage that results in muscle weakness on one side of the face. It may be idiopathic (Bell's palsy) or may have a detectable cause. Almost 80% of peripheral facial weakness cases are primary and the rest of them are secondary. The most frequent causes of secondary peripheral facial weakness are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immune disorders, drugs, degenerative diseases of the central nervous system, etc. The diagnosis relies upon the presence of typical signs and symptoms, blood chemistry tests, cerebrospinal fluid investigations, nerve conduction studies and neuroimaging methods (cerebral MRI, x-ray of the skull and mastoid). Treatment of secondary peripheral facial weakness is based on therapy for the underlying disorder, unlike the treatment of Bell's palsy that is controversial due to the lack of large, randomized, controlled, prospective studies. There are some indications that steroids or antiviral agents are beneficial but there are also studies that show no beneficial effect. Additional treatments include eye protection, physiotherapy, acupuncture, botulinum toxin, or surgery. Bell's palsy has a benign prognosis with complete recovery in about 80% of patients, 15% experience some mode of permanent nerve damage and severe consequences remain in 5% of patients.

  9. MEGACARYOCYTES IN THE PERIPHERAL CIRCULATION

    Science.gov (United States)

    Minot, George R.

    1922-01-01

    A megacaryocyte is seen commonly as an occasional cell in the peripheral blood of patients with myelogenous leucemia. Less commonly they appear in relatively large numbers. These giant cells also may occur in the blood under other conditions. Their presence is indicative of a bone marrow under intense strain. PMID:19868650

  10. [Ultrasound-guided peripheral catheterization].

    Science.gov (United States)

    Salleras-Duran, Laia; Fuentes-Pumarola, Concepció

    2016-01-01

    Peripheral catheterization is a technique that can be difficult in some patients. Some studies have recently described the use of ultrasound to guide the venous catheterization. To describe the success rate, time required, complications of ultrasound-guided peripheral venous catheterization. and patients and professionals satisfaction The search was performed in databases (Medline-PubMed, Cochrane Library, CINAHL and Cuiden Plus) for studies published about ultrasound-guided peripheral venous catheterization performed on patients that provided results on the success of the technique, complications, time used, patient satisfaction and the type of professional who performed the technique. A total of 21 studies were included. Most of them get a higher success rate 80% in the catheterization ecoguide and time it is not higher than the traditional technique. The Technical complications analyzed were arterial puncture rates and lower nerve 10%. In all studies measuring and comparing patient satisfaction in the art ecoguide is greater. Various professional groups perform the technique. The use of ultrasound for peripheral pipes has a high success rate, complications are rare and the time used is similar to that of the traditional technique. The technique of inserting catheters through ultrasound may be learned by any professional group performing venipuncture. Finally, it gets underscores the high patient satisfaction with the use of this technique. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  11. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  12. What Is Peripheral Artery Disease?

    Science.gov (United States)

    ... or bluish color to the skin A lower temperature in one leg compared to the other leg Poor nail growth on the toes and decreased hair growth on the legs Erectile dysfunction, especially among men who have diabetes Diagnosis Peripheral artery disease (P.A.D.) is diagnosed based ...

  13. Correlation and Agreement of Handheld Spirometry with Laboratory Spirometry in Allogeneic Hematopoietic Cell Transplant Recipients.

    Science.gov (United States)

    Cheng, Guang-Shing; Campbell, Angela P; Xie, Hu; Stednick, Zach; Callais, Cheryl; Leisenring, Wendy M; Englund, Janet A; Chien, Jason W; Boeckh, Michael

    2016-05-01

    Early detection of subclinical lung function decline may help identify allogeneic hematopoietic cell transplant (HCT) recipients who are at increased risk for late noninfectious pulmonary complications, including bronchiolitis obliterans syndrome. We evaluated the use of handheld spirometry in this population. Allogeneic HCT recipients enrolled in a single-center observational trial performed weekly spirometry with a handheld spirometer for 1 year after transplantation. Participants performed pulmonary function tests in an outpatient laboratory setting at 3 time points: before transplantation, at day 80 after transplantation, and at 1 year after transplantation. Correlation between the 2 methods was assessed by Pearson and Spearman correlations; agreement was assessed using Bland-Altman plots. A total of 437 subjects had evaluable pulmonary function tests. Correlation for forced expiratory volume in 1 second (FEV1) was r = .954 (P spirometry correlated well with laboratory spirometry after allogeneic HCT and may be useful for self-monitoring of patients for early identification of airflow obstruction. Copyright © 2016 American Society for Blood and Marrow Transplantation. All rights reserved.

  14. Allogeneic fetal stem cell transplantation to child with psychomotor retardation: A case report

    Directory of Open Access Journals (Sweden)

    Dajić Katerina

    2016-01-01

    Full Text Available Introduction. The consequences of autologous and allogeneic stem cell transplantation (stem cells of hematopoiesis, applied in adults and children suffering from leukemia or some other malignant disease, are well-known and sufficiently recognizable in pediatric clinical practice regardless of the indication for the treatment. However, the efficacy of fetal stem cell transplantation is unrecognizable when the indications are psychomotor retardation and epilepsy. Case Outline. With the exception of neurological psychiatric problems, a boy aged 9.5 years was in good general health before transplantation with allogeneic fetal stem cells. The main aim of allogeneic fetal stem cell transplantation was treatment of psychomotor retardation and epilepsy. After 13 months of treatment, he was admitted to hospital in a very serious, life-threatening condition due to sepsis and severe pleuropneumonia. The humoral immunity in the boy was adequate, unlike cellular immunity. The immune imbalance in terms of predominance of T-suppressor lymphocytes contributes to delayed and late development of sepsis and severe pleuropneumonia. The boy still shows the same severity of psychomotor retardation, dyslalia, epilepsy, strabismus and amblyopia. Conclusion. Implementation of fetal stem cell therapy for unconfirmed indications abuses the therapeutic approach, harms patients, misleads parents, and brings financial harm to the healthcare system of any country, including Serbia.

  15. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    Science.gov (United States)

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era

    Science.gov (United States)

    Ramadan, Safaa M.; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-01-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed. PMID:22689684

  17. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    Science.gov (United States)

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-07

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. © 2016 by The American Society of Hematology.

  18. Allogeneic BMT and patient eligibility based on psychosocial criteria: a survey of BMT professionals.

    Science.gov (United States)

    Foster, L W; McLellan, L J; Rybicki, L A; Dabney, J; Welsh, E; Bolwell, B J

    2006-01-01

    BMT professionals were compared regarding their willingness to proceed with allogeneic BMT given select psychosocial issues. A questionnaire was sent to 660 physician members of ASBMT, 92 social work members of BMT Special Interest Group, Association of Oncology Social Work, and 626 nurse members of BMT Special Interest Group, Oncology Nursing Society; 597 responded with a response rate of 43.5%. Items included background information, followed by 17 case vignettes; each represented a different psychosocial issue to which respondents indicated whether or not they would recommend proceeding with allogeneic BMT. In every vignette, at least 10% of respondents indicated they would not proceed. In six vignettes, at least 64% indicated do not proceed: suicidal ideation (86.8%), uses addictive illicit drugs (81.7%), history of noncompliance (80.5%), no lay caregiver (69.3%), alcoholic (64.8%), and mild dementia/Alzheimer's (64.4%). In 10 vignettes, at least 73% indicated proceed. On four vignettes, professional subgroups differed in their recommendation on whether or not to proceed with allogeneic BMT. Qualitative data suggest that this decision is contingent on the perceived acuity, severity, and currency of the psychosocial issue, patient ability to comply with treatment given the issue, and its manageability as a risk factor for treatment related vulnerability and outcomes.

  19. Feasibility of combination allogeneic stem cell therapy for spinal cord injury: a case report

    Directory of Open Access Journals (Sweden)

    Ichim Thomas E

    2010-11-01

    Full Text Available Abstract Cellular therapy for spinal cord injury (SCI is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI.

  20. Allogeneic radiation chimeras respond to TNP-modified donor and host targets

    International Nuclear Information System (INIS)

    Lattime, E.C.; Gershon, H.E.; Stutman, O.

    1980-01-01

    Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 x DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 x CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells

  1. Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

    International Nuclear Information System (INIS)

    McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

    1981-01-01

    We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease

  2. PD-1hiTIM-3+ T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation

    International Nuclear Information System (INIS)

    Kong, Y; Zhang, J; Claxton, D F; Ehmann, W C; Rybka, W B; Zhu, L; Zeng, H; Schell, T D; Zheng, H

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1 hi TIM-3 + cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1 hi TIM-3 + T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing T N and T EMRA subsets. Importantly, increase of PD-1 hi TIM-3 + cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation

  3. Screening and monitoring of MPL W515L mutation with real-time PCR in patients with myelofibrosis undergoing allogeneic-SCT.

    Science.gov (United States)

    Alchalby, H; Badbaran, A; Bock, O; Fehse, B; Bacher, U; Zander, A R; Kröger, N

    2010-09-01

    Monitoring of minimal residual disease (MRD) after allogeneic (allo)-SCT for myelofibrosis (MF) allows recognizing the depth of remission and thus guides application of appropriate therapeutic interventions. MPL W515L/K mutations, which are detected in 5-10% of JAK2V617F-negative patients, may be useful for this purpose. Using a highly sensitive quantitative PCR method, we tested 90 patients with MF who underwent allo-SCT for the presence of MPL W515L/K mutations. Two patients with primary MF were found to harbor MPLW515L while no patient was positive for MPLW515K mutation. Both patients were JAK2V617F negative and cleared the mutation rapidly after allo-SCT and remained negative for a median follow-up of 19 months. The results of molecular monitoring correlated well with other remission parameters such as normalization of peripheral blood counts and morphology and complete donor chimerism. We conclude that MPLW515L can be cleared after allo-SCT and hence may be used as an MRD marker in a proportion of JAK2V617F-negative MF patients.

  4. Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.

    Science.gov (United States)

    Koyama, M; Hashimoto, D; Nagafuji, K; Eto, T; Ohno, Y; Aoyama, K; Iwasaki, H; Miyamoto, T; Hill, G R; Akashi, K; Teshima, T

    2014-01-01

    Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

  5. Immune Response Generated With the Administration of Autologous Dendritic Cells Pulsed With an Allogenic Tumoral Cell-Lines Lysate in Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma

    Directory of Open Access Journals (Sweden)

    Daniel Benitez-Ribas

    2018-04-01

    Full Text Available Background and objectiveDiffuse intrinsic pontine glioma (DIPG is a lethal brainstem tumor in children. Dendritic cells (DCs have T-cell stimulatory capacity and, therefore, potential antitumor activity for disease control. DCs vaccines have been shown to reactivate tumor-specific T cells in both clinical and preclinical settings. We designed a phase Ib immunotherapy (IT clinical trial with the use of autologous dendritic cells (ADCs pulsed with an allogeneic tumors cell-lines lysate in patients with newly diagnosed DIPG after irradiation (radiation therapy.MethodsNine patients with newly diagnosed DIPG met enrollment criteria. Autologous dendritic cell vaccines (ADCV were prepared from monocytes obtained by leukapheresis. Five ADCV doses were administered intradermally during induction phase. In the absence of tumor progression, patients received three boosts of tumor lysate every 3 months during the maintenance phase.ResultsVaccine fabrication was feasible in all patients included in the study. Non-specific KLH (9/9 patients and specific (8/9 patients antitumor response was identified by immunologic studies in peripheral blood mononuclear cells (PBMC. Immunological responses were also confirmed in the T lymphocytes isolated from the cerebrospinal fluid (CSF of two patients. Vaccine administration resulted safe in all patients treated with this schema.ConclusionThese preliminary results demonstrate that ADCV preparation is feasible, safe, and generate a DIPG-specific immune response detected in PBMC and CSF. This strategy shows a promising backbone for future schemas of combination IT.

  6. Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

    Science.gov (United States)

    Locatelli, F; Masetti, R; Rondelli, R; Zecca, M; Fagioli, F; Rovelli, A; Messina, C; Lanino, E; Bertaina, A; Favre, C; Giorgiani, G; Ripaldi, M; Ziino, O; Palumbo, G; Pillon, M; Pession, A; Rutella, S; Prete, A

    2015-02-01

    We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.

  7. A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display.

    Science.gov (United States)

    Baskar, Sivasubramanian; Suschak, Jessica M; Samija, Ivan; Srinivasan, Ramaprasad; Childs, Richard W; Pavletic, Steven Z; Bishop, Michael R; Rader, Christoph

    2009-11-12

    Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only potentially curative treatment available for patients with B-cell chronic lymphocytic leukemia (B-CLL). Here, we show that post-alloHSCT antibody repertoires can be mined for the discovery of fully human monoclonal antibodies to B-CLL cell-surface antigens. Sera collected from B-CLL patients at defined times after alloHSCT showed selective binding to primary B-CLL cells. Pre-alloHSCT sera, donor sera, and control sera were negative. To identify post-alloHSCT serum antibodies and subsequently B-CLL cell-surface antigens they recognize, we generated a human antibody-binding fragment (Fab) library from post-alloHSCT peripheral blood mononuclear cells and selected it on primary B-CLL cells by phage display. A panel of Fab with B-CLL cell-surface reactivity was strongly enriched. Selection was dominated by highly homologous Fab predicted to bind the same antigen. One Fab was converted to immunoglobulin G1 and analyzed for reactivity with peripheral blood mononuclear cells from B-CLL patients and healthy volunteers. Cell-surface antigen expression was restricted to primary B cells and up-regulated in primary B-CLL cells. Mining post-alloHSCT antibody repertoires offers a novel route to discover fully human monoclonal antibodies and identify antigens of potential therapeutic relevance to B-CLL and possibly other cancers. Trials described herein were registered at www.clinicaltrials.gov as nos. NCT00055744 and NCT00003838.

  8. Systemic Administration of Allogeneic Mesenchymal Stem Cells Does Not Halt Osteoporotic Bone Loss in Ovariectomized Rats.

    Directory of Open Access Journals (Sweden)

    Shuo Huang

    Full Text Available Mesenchymal stem cells (MSCs have innate ability to self-renew and immunosuppressive functions, and differentiate into various cell types. They have become a promising cell source for treating many diseases, particular for bone regeneration. Osteoporosis is a common metabolic bone disorder with elevated systemic inflammation which in turn triggers enhanced bone loss. We hypothesize that systemic infusion of MSCs may suppress the elevated inflammation in the osteoporotic subjects and slow down bone loss. The current project was to address the following two questions: (1 Will a single dose systemic administration of allogenic MSCs have any effect on osteoporotic bone loss? (2 Will multiple administration of allogenic MSCs from single or multiple donors have similar effect on osteoporotic bone loss? 18 ovariectomized (OVX rats were assigned into 3 groups: the PBS control group, MSCs group 1 (receiving 2x106 GFP-MSCs at Day 10, 46, 91 from the same donor following OVX and MSCs group 2 (receiving 2x106 GFP-MSCs from three different donors at Day 10, 46, 91. Examinations included Micro-CT, serum analysis, mechanical testing, immunofluorescence staining and bone histomorphometry analysis. Results showed that BV/TV at Day 90, 135, BMD of TV and trabecular number at Day 135 in the PBS group were significantly higher than those in the MSCs group 2, whereas trabecular spacing at Day 90, 135 was significantly smaller than that in MSCs group 2. Mechanical testing data didn't show significant difference among the three groups. In addition, the ELISA assay showed that level of Rantes in serum in MSCs group 2 was significantly higher than that of the PBS group, whereas IL-6 and IL-10 were significantly lower than those of the PBS group. Bone histomorphometry analysis showed that Oc.S/BS and Oc.N/BS in the PBS group were significant lower than those in MSCs group 2; Ob.S/BS and Ob.N/BS did not show significant difference among the three groups. The current study

  9. Angioplasty and stent placement - peripheral arteries - discharge

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000234.htm Angioplasty and stent placement - peripheral arteries - discharge To use the sharing ... peripheral artery). You may have also had a stent placed. To perform the procedure: Your doctor inserted ...

  10. Hypothyroidism: Can It Cause Peripheral Neuropathy?

    Science.gov (United States)

    Hypothyroidism: Can it cause peripheral neuropathy? Can hypothyroidism cause peripheral neuropathy and, if so, how is it treated? Answers from Todd B. Nippoldt, M.D. Hypothyroidism — a condition in which your ...

  11. Development of PET Imaging to Visualize Activated Macrophages Accumulated in the Transplanted iPSc-Derived Cardiac Myocytes of Allogeneic Origin for Detecting the Immune Rejection of Allogeneic Cell Transplants in Mice.

    Directory of Open Access Journals (Sweden)

    Noriyuki Kashiyama

    Full Text Available Allogeneic transplantation (Tx of induced pluripotent stem cells (iPSCs is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET imaging targets translocator protein (TSPO, which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714 is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group, or Balb/c mice as an allogeneic model (allogeneic Tx group. 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune

  12. Coaching Peripheral Vision Training for Soccer Athletes

    Science.gov (United States)

    Marques, Nelson Kautzner, Jr.

    2010-01-01

    Brazilian Soccer began developing its current emphasis on peripheral vision in the late 1950s, by initiative of coach of the Canto do Rio Football Club, in Niteroi, Rio de Janeiro, a pioneer in the development of peripheral vision training in soccer players. Peripheral vision training gained world relevance when a young talent from Canto do Rio,…

  13. Peripheral Neuropathy – Clinical and Electrophysiological Considerations

    Science.gov (United States)

    Chung, Tae; Prasad, Kalpana; Lloyd, Thomas E.

    2013-01-01

    This article is a primer on the pathophysiology and clinical evaluation of peripheral neuropathy for the radiologist. Magnetic resonance neurography (MRN) has utility in the diagnosis of many focal peripheral nerve lesions. When combined with history, examination, electrophysiology, and laboratory data, future advancements in high-field MRN may play an increasingly important role in the evaluation of patients with peripheral neuropathy. PMID:24210312

  14. Monitoring sweep in peripheral waterflood

    International Nuclear Information System (INIS)

    Rouser, B.J.; Al-Askar, Y.A.; Hassoun, T.H.

    1991-01-01

    This paper examines the techniques used and the results obtained in monitoring the water advance in a peripheral waterflood of a carbonate reservoir. The peripheral pattern used in the subject reservoir gives a water advanced similar to that obtained in a water drive reservoir. However, monitoring this particular reservoir is complicated by the use of a low salinity brine for flooding and the areal shape of the reservoir. The use of pulsed neutron capture logging in conjunction with production logging has been effective in differentiating between oil and water in porous zones in existing producers. The use of the two logs has been successful despite the problems normally encountered when logging open hole completions in a reservoir being flooded with a low salinity brine. Results have been confirmed and enhanced by open hole logs of new wells being drilled in the water invaded areas

  15. Peripheral nerve conduits: technology update

    Directory of Open Access Journals (Sweden)

    Arslantunali D

    2014-12-01

    Full Text Available D Arslantunali,1–3,* T Dursun,1,2,* D Yucel,1,4,5 N Hasirci,1,2,6 V Hasirci,1,2,7 1BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU, Ankara, Turkey; 2Department of Biotechnology, METU, Ankara, Turkey; 3Department of Bioengineering, Gumushane University, Gumushane, Turkey; 4Faculty of Engineering, Department of Medical Engineering, Acibadem University, Istanbul, Turkey; 5School of Medicine, Department of Histology and Embryology, Acibadem University, Istanbul, Turkey; 6Department of Chemistry, Faculty of Arts and Sciences, METU, Ankara, Turkey; 7Department of Biological Sciences, Faculty of Arts and Sciences, METU, Ankara, Turkey *These authors have contributed equally to this work Abstract: Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers and designs (tubular, fibrous, and matrix type are being presented. Keywords: peripheral nerve injury, natural biomaterials, synthetic biomaterials

  16. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...SUPPLEMENTARY NOTES 14. ABSTRACT In current war trauma, 20-30% of all extremity injuries and >80% of penetrating injuries being associated with peripheral nerve...through both axonal advance and in revascularization of the graft following placement. We are confident that this technology may allow us to

  17. Communication, Consumption and Peripheral Politics

    Directory of Open Access Journals (Sweden)

    NÍZIA VILLAÇA

    2009-02-01

    Full Text Available This essay analyses central/peripheral dynamics and its new semantics in the big scenario of globalization. The processes of hybridization between the local and the global spaces are discussed focusing the strategies of inclusion and exclusion through some examples from media and cultural industry. The methodology helps to reflect about the theme using elements of epistemology communication, consumer society and cultural studies.

  18. Peripheral facial palsy in children.

    Science.gov (United States)

    Yılmaz, Unsal; Cubukçu, Duygu; Yılmaz, Tuba Sevim; Akıncı, Gülçin; Ozcan, Muazzez; Güzel, Orkide

    2014-11-01

    The aim of this study is to evaluate the types and clinical characteristics of peripheral facial palsy in children. The hospital charts of children diagnosed with peripheral facial palsy were reviewed retrospectively. A total of 81 children (42 female and 39 male) with a mean age of 9.2 ± 4.3 years were included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma, congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%) patients had recurrent attacks. In patients with Bell palsy, female/male and right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a history of preceding infection. The overall rate of complete recovery was 98.4%. A wide variety of disorders can present with peripheral facial palsy in children. Therefore, careful investigation and differential diagnosis is essential. © The Author(s) 2013.

  19. Allogeneic amniotic membrane-derived mesenchymal stromal cell transplantation in a porcine model of chronic myocardial ischemia

    Directory of Open Access Journals (Sweden)

    Kimura M

    2012-01-01

    Full Text Available Introduction. Amniotic membrane contains a multipotential stem cell population and is expected to possess the machinery to regulate immunological reactions. We investigated the safety and efficacy of allogeneic amniotic membrane-derived mesenchymal stromal cell (AMSC transplantation in a porcine model of chronic myocardial ischemia as a preclinical trial. Methods. Porcine AMSCs were isolated from amniotic membranes obtained by cesarean section just before delivery and were cultured to increase their numbers before transplantation. Chronic myocardial ischemia was induced by implantation of an ameroid constrictor around the left circumflex coronary artery. Four weeks after ischemia induction, nine swine were assigned to undergo either allogeneic AMSC transplantation or normal saline injection. Functional analysis was performed by echocardiography, and histological examinations were carried out by immunohistochemistry 4 weeks after AMSC transplantation. Results. Echocardiography demonstrated that left ventricular ejection fraction was significantly improved and left ventricular dilatation was well attenuated 4 weeks after AMSC transplantation. Histological assessment showed a significant reduction in percentage of fibrosis in the AMSC transplantation group. Injected allogeneic green fluorescent protein (GFP-expressing AMSCs were identified in the immunocompetent host heart without the use of any immunosuppressants 4 weeks after transplantation. Immunohistochemistry revealed that GFP colocalized with cardiac troponin T and cardiac troponin I. Conclusions. We have demonstrated that allogeneic AMSC transplantation produced histological and functional improvement in the impaired myocardium in a porcine model of chronic myocardial ischemia. The transplanted allogeneic AMSCs survived without the use of any immunosuppressants and gained cardiac phenotype through either their transdifferentiation or cell fusion.

  20. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    International Nuclear Information System (INIS)

    Belkacemi, Yazid; Labopin, Myriam; Hennequin, Christophe; Hoffstetter, Sylvette; Mungai, Raffaello; Wygoda, Marc; Lundell, Marie; Finke, Jurgen; Aktinson, Chris; Lorchel, Frederic; Durdux, Catherine; Basara, Nadezda

    2007-01-01

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population

  1. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

    Science.gov (United States)

    Berglund, A K; Schnabel, L V

    2017-07-01

    Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

  2. Peripheral doses from pediatric IMRT

    International Nuclear Information System (INIS)

    Klein, Eric E.; Maserang, Beth; Wood, Roy; Mansur, David

    2006-01-01

    Peripheral dose (PD) data exist for conventional fields (≥10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 to 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10 -10 scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from

  3. Allotransplanted neurons used to repair peripheral nerve injury do not elicit overt immunogenicity.

    Directory of Open Access Journals (Sweden)

    Weimin Liu

    Full Text Available A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05 while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001. Major histocompatibility complex I (MHC I molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold

  4. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

  5. Similar effect of autologous and allogeneic cell therapy for ischemic heart disease : Systematic review and meta-analysis of large animal studies

    NARCIS (Netherlands)

    Jansen of Lorkeers, Sanne J.; Eding, Joep Egbert Coenraad; Vesterinen, Hanna Mikaela; van der Spoel, Tycho Ids Gijsbert; Sena, Emily Shamiso; Duckers, Henricus Johannes; Doevendans, Pieter Adrianus; Macleod, Malcolm Robert; Chamuleau, Steven Anton Jozef

    2015-01-01

    Rationale: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell

  6. Progression and CSF Inflammation after Eradication of Oligoclonal Bands in an MS Patient Treated with Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma

    DEFF Research Database (Denmark)

    Braendstrup, P; Langkilde, Annika; Schreiber, K

    2012-01-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.......Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases....

  7. Hepatic abscess versus peripheral cholangiocarcinoma: Sonographic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Chung, Kyoo Byung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of); Lee, Chang Hee [Kunkuk University College of Medicine, Chung-Ju Hospital, Chung-Ju (Korea, Republic of)

    2000-12-15

    To find out the sonographic findings that are useful to differentiate hepatic abscess from peripheral cholangiocarcinoma. Twenty-two hepatic abscesses and 22 peripheral cholangiocarcinomas which had been confirmed histologically were included in this study. Objective points were echo characteristics of the lesion, internal septation, presence of peripheral low echoic rim, demarcation from normal liver(well or poorly defined), posterior enhancement, multiplicity, dilatation of bile duct(obstructive or non-obstructive), intrahepatic duct stone, pleural effusion, and intra-abdominal fluid collection. Echo characteristics of the lesion were classified in-to four types. Type I; Predominantly echogenic with hypoechoic portion, type II; Echogenic without hypoechoic portion, type III; Predominantly hypoechoic with echogenic portion, type IV; Hypoechoic without echogenic portion. 1)Nine abscesses and 2 peripheral cholangiocarcinomas were type I(p=0.037), 2)One abscess and 18 peripheral cholangiocarcinomas were type II(p=0.001), 3)Seven abscesses and none of peripheral cholangiocarcinomas were type III(p=0.001), 4)Five abscesses and 2 peripheral cholangiocarcinomas were type IV(p=0.410). Only 7 abscesses showed internal septations(p=0.013). One abscess and 9 peripheral cholangiocarcinomas showed peripheral hypoechoic halos(p=0.012). Only 9 peripheral cholangiocarcinomas showed obstructive bile duct dilatation (p=0.001). There were no statistically significant differences between abscess and peripheral cholangiocarcinoma on other objective points. Predominantly echogenic with hypoechoic portion, predominantly hypoechoic with echogenic portion, and internal septation are the features suggestive of hepatic abscess, and echogenic without hypoechoic portion, peripheral hypoechoic halo, obstructive bile duct dilatation are suggestive of peripheral cholangiocarcinoma. Therefore these sonographic findings are helpful to differentiate hepatic abscess from peripheral

  8. Do autologous blood transfusion systems reduce allogeneic blood transfusion in total knee arthroplasty?

    Science.gov (United States)

    Pawaskar, Aditya; Salunke, Abhijeet Ashok; Kekatpure, Aashay; Chen, Yongsheng; Nambi, G I; Tan, Junhao; Sonawane, Dhiraj; Pathak, Subodhkumar

    2017-09-01

    To study whether autologus blood transfusion systems reduce the requirement of allogneic blood transfusion in patients undergoing total knee arthroplasty. A comprehensive search of the published literature with PubMed, Scopus and Science direct database was performed. The following search terms were used: (total knee replacement) OR (total knee arthroplasty) OR (TKA) AND (blood transfusion) OR (autologous transfusion) OR (autologous transfusion system). Using search syntax, a total of 748 search results were obtained (79 from PubMed, 586 from Science direct and 83 from Scopus). Twenty-one randomized control trials were included for this meta-analysis. The allogenic transfusion rate in autologus blood transfusion (study) group was significantly lower than the control group (28.4 and 53.5 %, respectively) (p value 0.0001, Relative risk: 0.5). The median units of allogenic blood transfused in study control group and control group were 0.1 (0.1-3.0) and 1.3 (0.3-2.6), respectively. The median hospital stay in study group was 9 (6.7-15.6) days and control group was 8.7 (6.6-16.7) days. The median cost incurred for blood transfusion per patient in study and control groups was 175 (85.7-260) and 254.7 (235-300) euros, respectively. This meta-analysis demonstrates that the use of auto-transfusion systems is a cost-effective method to reduce the need for and quantity of allogenic transfusion in elective total knee arthroplasty. Level I.

  9. Electron beam irradiation to the allogeneic, xenogenic and synthetic bone materials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Soung Min; Park, Min Woo; Jeong, Hyun Oh [School of Dentistry Seoul National University, Seoul (Korea, Republic of); and others

    2013-07-01

    For the development of the biocompatible bony regeneration materials, allogenic, xenogenic and synthetic bone were irradiated by electron beam to change the basic components and structures. For the efficient electron beam irradiating condition of these allogenic, xenogenic and artificial bone substitutes, the optimal electron beam energy and their individual dose were established, to maximize the bony regeneration capacity. Commercial products of four allogenic bones, such as Accell (ISOTIS OrthogBiologics Co., USA), Allotis (Korea Bone Bank Co., Korea), Oragraft (LifeNet Co., USA), and Orthoblast (Integra Orthobiologics Inc., USA), six xenogenic bones, such as BBP (OscoTec Co., Korea), Bio-cera (OscoTec Co., Korea), Bio-oss (Geistlich Pharma AG, Switzerland), Indu-cera (OscoTec Co., Korea), OCS-B (Nibec Co., Korea), and OCS-H (Nibec Co., Korea), and six synthetic bones, such as BMP (Couellmedi Co., Korea), BoneMedik (Meta Biomed Co., Korea), Bone plus (Megagen Co., Korea), MBCP (Biomatlante Co., France), Osteon (Genoss Co., Korea), and Osteogen (Impladent LTD., USA), were used. We used 1.0 and 2.0 MeV superconduction accelerator, and/or microtrone with different individual 60, 120 kGy irradiation dose. Different dose irradiated specimens were divided 6 portions each, so total 360 groups were prepared. 4 portions were analyzed each by elementary analysis using FE-SEM (Field Emission Scanning Microscopy) and another 2 portions were grafted to the calvarial defect of Sprague-Dawley rat, following histologic, immunohistochemical analysis and TEM study were processed at the 8th and 16th weeks, in vivo. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MEST)

  10. Frozen allogeneic human epidermal cultured sheets for the cure of complicated leg ulcers.

    Science.gov (United States)

    Bolívar-Flores, Y J; Kuri-Harcuch, W

    1999-08-01

    Skin ulcers due to venous stasis or diabetes are common among the elderly and are difficult to treat. Repeated applications of cell-based products have been reported to result in cure or improvement of leg ulcers of small size in a fraction of patients. To examine the effects of frozen human allogeneic epidermal cultures for the treatment of acute and chronic ulcers. We treated a series of 10 consecutive patients with leg ulcers of different etiology and duration with frozen human allogeneic epidermal cultures stored frozen and thawed for 5-10 minutes at room temperature before application. Three patients had ulcers with exposed Achilles or extensor tendon. The ulcers treated were as large as 160 cm2 in area and of up to 20-years' duration. After preliminary preparation of the wounds by debridement to remove necrotic tissue and application of silver sulfadiazine to control infection, thawed cultures were applied biweekly from 2 to 15 times depending on the size and complexity of the ulcer. All ulcers healed, including those with tendon exposure. After the first few applications, granulation tissue formed in the ulcer bed and on exposed tendons, and epidermal healing took place through proliferation and migration of cells from the margins of the wound. The time required for complete healing ranged from 1 to 31 weeks after the first application. The use of frozen human allogeneic epidermal cultures is a safe and effective treatment for venous or diabetic ulcers, even those with tendon exposure. It seems possible that any leg ulcer will be amenable to successful treatment by this method.

  11. Reduced use of allogeneic platelets through high-yield perioperative autologous plateletpheresis and reinfusion.

    Science.gov (United States)

    Alberts, Melissa; Bandarenko, Nicholas; Gaca, Jeffrey; Lockhart, Evelyn; Milano, Carmelo; Alexander, Stanlin; Linder, Dean; Lombard, Frederick W; Welsby, Ian J

    2014-05-01

    Intraoperative autologous platelet (PLT) collection as part of a multimodal blood conservation program carries a Class IIa recommendation from the Societies of Thoracic Surgeons and Cardiovascular Anesthesiologists, but achieving a suitable PLT yield limits its application. A novel, autologous, intraoperative, high-yield plateletpheresis collection program was established and retrospectively analyzed to identify potential improvements over previously reported plateletpheresis protocols. Targeting complex cardiothoracic surgery patients without recent anti-PLT agents, thrombocytopenia, or severe anemia, the program aimed to achieve a PLT yield of at least one standard apheresis unit (3.0 × 10(11) ) within 60 to 90 minutes and using an automated plateletpheresis device (Trima, Terumo BCT). Anesthetized and invasively monitored patients underwent plateletpheresis via a large-bore, indwelling central line placed for the surgery. Collection-related data for quality control purposes and subsequent PLT transfusion requirements were analyzed and reported. Forty-two patients donated autologous PLTs between 2011 and 2012. PLT yield was 4.5 (3.9-5.0) × 10(11) , which significantly exceeds previously reported yields, and procedure duration was 53.2 (48.4-57.9) minutes. As anticipated, postcollection PLT count decreased from 268 (242-293) × 10(9) to 182 (163-201) × 10(9) /L; hypocalcemia was minimized by infusion of 1 g of CaCl2 . Autologous PLT yield was inversely correlated with allogeneic PLT use, and avoidance of allogeneic PLT transfusion was increased when the autologous yield was the equivalent of 2 or more apheresis units. High-yield, intraoperative autologous PLT collection is achievable using an automated plateletpheresis device. Initial experience shows a reduction in reliance on allogeneic PLTs for complex cardiothoracic surgery. © 2013 American Association of Blood Banks.

  12. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    Tsuno, Hiroaki; Yoshida, Toshiko; Nogami, Makiko; Koike, Chika; Okabe, Motonori; Noto, Zenko; Arai, Naoya; Noguchi, Makoto; Nikaido, Toshio

    2012-01-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAMα cells and induced to osteogenic status—their in vivo osteogenesis was subsequently investigated in rats. It was found that HAMα cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAMα cells. The expression of osteocalcin mRNA was increased in HAMα cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAMα cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: ► Human amniotic mesenchymal cells include cells (HAMα cells) that have the properties of MSCs. ► HAMα cells have excellent osteogenic differentiation potential. ► Osteogenic differentiation ability of HAMα was amplified by calcium phosphate scaffolds. ► HAMα cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  13. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  14. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

    Science.gov (United States)

    Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

    2014-10-01

    Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

    Science.gov (United States)

    Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

    2003-11-01

    To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

  16. How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

    Directory of Open Access Journals (Sweden)

    Sinem Civriz Bozdağ

    2012-03-01

    Full Text Available Clinical course of H1N1 infection in Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT patients is contraversial. We report three AHSCT patients who were infected with Influenza A/H1N1 infection. All of the patients were diagnosed with different hematological diagnosis and were at different stages of transplantation.All of them were treated with oseltamivir,zanamivir was switched with oseltamivir in one patient. All of the three patients were survived without any complication. Swine flu, can display with different courses and progress with bacterial or other viral infections in immunsupressed patients.

  17. Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in Acute Myeloid Leukemia

    DEFF Research Database (Denmark)

    Østgård, Lene Sofie Granfeldt; Lund, Jennifer L; Nørgaard, Jan Maxwell

    2018-01-01

    To examine the outcome of allogeneic stem cell transplantation (HSCT) in first complete remission (CR1) compared to chemotherapy alone in a population-based setting, we identified a cohort of acute myeloid leukemia (AML) patients aged 15-70 years diagnosed between 2000-2014 in Denmark. Using...... the Danish National Acute Leukemia Registry, we compared relapse risk, relapse-free survival (RFS), and overall survival between patients with non-favorable cytogenetic features receiving post-remission therapy with conventional chemotherapy-only versus those undergoing HSCT in CR1. To minimize immortal time...

  18. Indication of total body irradiation in adult allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kasai, Masaharu (Sapporo Hokuyu Hospital (Japan). Artificial Organ and Transplantation Hospital)

    1992-10-01

    Indication of total body irradiation (TBI) in adult allogeneic bone marrow transplantation was discussed in comparison with non-TBI method of busulfan and cyclophosphamide (BU+CY). Each method has unique advantages and disadvantages. Concerning adverse effects of interstitial pneumonia, liver dysfunction and so on, there are no significant differences in both methods. TBI method should be preferably indicated for lymphatic leukemias and leukemias involving central nervous systems. It is important to clarify what kinds of combination regimen depending on the type and the stage of disease are most suitable for the longer survival of patients with leukemia or aplastic anemia by multicentric randomized study. (author).

  19. Risk factors for treatment failure after allogeneic transplantation of patients with CLL

    DEFF Research Database (Denmark)

    Schetelig, J; de Wreede, L C; van Gelder, M

    2017-01-01

    For young patients with high-risk CLL, BTK-/PI3K-inhibitors or allogeneic stem cell transplantation (alloHCT) are considered. Patients with a low risk of non-relapse mortality (NRM) but a high risk of failure of targeted therapy may benefit most from alloHCT. We performed Cox regression analyses......, performance status, prior autologous HCT, remission status and sex-mismatch had a significant impact, whereas del(17p) did not. The model-based prediction of 5-year EFS was 55% and 64%, respectively, for male and female good-risk patients. Good-risk transplant candidates with high-risk CLL and limited...

  20. Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.

    Directory of Open Access Journals (Sweden)

    Marilène Binsfeld

    Full Text Available Multiple myeloma (MM is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD.Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor or autologous (Balb/cJ donor transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses

  1. Allogenic bone rods with freeze drying and gamma rays irradiation for treatment of fracture

    International Nuclear Information System (INIS)

    Zhou Zhenbin

    1999-01-01

    Opened reduction and internal fixation are the usual treatment of fracture, but both methods need a second operation for removal implants. The benefits of the bone rods are that they can avoid the removement of internal fixation and will be absorbed spontaneously. The bone rods are made of allogeneic compact bones with freeze-drying and gamma rays irradiation supplied by Shanxi Provincial Tissue Bank. The purpose of this study is to evaluate allograft reaction, the stability of the internal fixation, osteoinduction in the treatment of fracture using allogeneic bone rods with freeze drying and gamma rays irradiation. From May 1997 to May 1998, fourteen cases (male 12, female 2) of treatment were reviewed. The mean age was 37.3 (21-5 1). There were 3 medial malleolus fractures, 7 tibia and fibula fractures, 1 ulna and radius fracture, 1 lateral condyle of humerus fracture. The clinical results were satisfactory. Because the strength of the bone rods are weaker than that of screws, the bone rods are only indicated in the fixation of cancellous bones fracture and unloaded bone fracture. It can be used as a supplementary fixation of loaded bone. It is not indicated for fixation of comminuted fracture. More than two bone rods may be used in the fixation of fracture in order to get stability of the fracture and decrease stress between rods which will prevent the break of the bone rods. Allogeneic bone rods with freeze-drying and gamma rays irradiation can be used as implants of non-immunogenicity. There are no allograft reactions in all cases (including fever, leukocytosis, exudation or swelling in the wound). Although plenty of experimental studies have showed that freeze drying with gamma rays irradiation (below 50 KGy) would not destroy BMP of bone allograft, but there is no osteoinduction in our cases. The healing of a fracture and bridging external callus are similar as other operations. This new technique may have the following advantages compare with the screws: 1

  2. Transplantation of cryopreserved allogeneic bone marrow after its long-term storage to lethally irradiated dogs

    International Nuclear Information System (INIS)

    Novikova, N.N.; Fedotenkov, A.G.; Sukyasyan, G.V.; Timakova, L.A.

    1982-01-01

    The study of the dog bone marrow preserved at -196 deg C during 6-12 years has shown that in the body of lethally irradiated animals (8Gy), due to the antigenic difference in the tissues of the donor and the irradiated recipients, the cells of cryopreserved allogeneic bone marrow were differentiated by the lymphoid type similar to that observed in transplantation of freshly prepared myelocaryocytes. However, their proliferative activity in the period of active lymphocyte transformation was quantitatively less manifest than in freshly transplanted cells. The results of the study evidence that the bone marrow cells cryopreserved during 6-12 years retain their functional activity

  3. Post-influenzal triazole-resistant aspergillosis following allogeneic stem cell transplantation.

    Science.gov (United States)

    Talento, Alida Fe; Dunne, Katie; Murphy, Niamh; O'Connell, Brian; Chan, Grace; Joyce, Eimear Ann; Hagen, Ferry; Meis, Jacques F; Fahy, Ruauri; Bacon, Larry; Vandenberge, Elisabeth; Rogers, Thomas R

    2018-03-23

    Influenza virus infection is now recognised as a risk factor for invasive pulmonary aspergillosis (IPA). Delays in diagnosis contribute to delayed commencement of antifungal therapy. Additionally, the emergence of resistance to first-line triazole antifungal agents puts emphasis on early detection to prevent adverse outcomes. We present 2 allogeneic stem cell transplant patients who developed IPA due to triazole-resistant Aspergillus fumigatus following influenza infection. We underline the challenges faced in the management of these cases, the importance of early diagnosis and need for surveillance given the emergence of triazole-resistance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Solid organ transplantation after allogeneic hematopoietic stem cell transplantation: a retrospective, multicenter study of the EBMT

    DEFF Research Database (Denmark)

    Koenecke, C; Hertenstein, B; Schetelig, J

    2010-01-01

    To analyze the outcome of solid organ transplantation (SOT) in patients who had undergone allogeneic hematopoietic stem cell transplantation (HSCT), a questionnaire survey was carried out within 107 European Group of Blood and Marrow Transplantation centers. This study covered HSCT between 1984...... for underlying malignant diseases was 4% at 5 years (95% CI, 0% to 12%). In summary, this study shows that selected patients receiving SOT after HSCT have a remarkably good overall and organ survival. These data indicate that SOT should be considered in selected patients with single organ failure after HSCT....

  5. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

    International Nuclear Information System (INIS)

    Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

    1980-01-01

    A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation

  6. Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Andersen, J; Heilmann, C; Jacobsen, N

    2006-01-01

    The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti.......002), followed by VP-16 (184%, P=0.03), cyclophosphamide (129%, P=0.03) and total body irradiation (148%, P=0.0005). Administration of i.v. busulfan (Busilvex; BU) was not associated with significant changes in sTNFRI levels. At day 0 (the day of stem cell infusion) the sTNFRI levels were not only elevated...

  7. Clinicopathologic findings following intra-articular injection of autologous and allogeneic placentally derived equine mesenchymal stem cells in horses.

    Science.gov (United States)

    Carrade, Danielle D; Owens, Sean D; Galuppo, Larry D; Vidal, Martin A; Ferraro, Gregory L; Librach, Fred; Buerchler, Sabine; Friedman, Michael S; Walker, Naomi J; Borjesson, Dori L

    2011-04-01

    The development of an allogeneic mesenchymal stem cell (MSC) product to treat equine disorders would be useful; however, there are limited in vivo safety data for horses. We hypothesized that the injection of self (autologous) and non-self (related allogeneic or allogeneic) MSC would not elicit significant alterations in physical examination, gait or synovial fluid parameters when injected into the joints of healthy horses. Sixteen healthy horses were used in this study. Group 1 consisted of foals (n = 6), group 2 consisted of their dams (n = 5) and group 3 consisted of half-siblings (n = 5) to group 1 foals. Prior to injection, MSC were phenotyped. Placentally derived MSC were injected into contralateral joints and MSC diluent was injected into a separate joint (control). An examination, including lameness evaluation and synovial fluid analysis, was performed at 0, 24, 48 and 72 h post-injection. MSC were major histocompatibility complex (MHC) I positive, MHC II negative and CD86 negative. Injection of allogeneic MSC did not elicit a systemic response. Local responses such as joint swelling or lameness were minimal and variable. Intra-articular MSC injection elicited marked inflammation within the synovial fluid (as measured by nucleated cell count, neutrophil number and total protein concentration). However, there were no significant differences between the degree and type of inflammation elicited by self and non-self-MSC. The healthy equine joint responds similarly to a single intra-articular injection of autologous and allogeneic MSC. This pre-clinical safety study is an important first step in the development of equine allogeneic stem cell therapies.

  8. Peripheral Mechanisms of Ischemic Myalgia

    Directory of Open Access Journals (Sweden)

    Luis F. Queme

    2017-12-01

    Full Text Available Musculoskeletal pain due to ischemia is present in a variety of clinical conditions including peripheral vascular disease (PVD, sickle cell disease (SCD, complex regional pain syndrome (CRPS, and even fibromyalgia (FM. The clinical features associated with deep tissue ischemia are unique because although the subjective description of pain is common to other forms of myalgia, patients with ischemic muscle pain often respond poorly to conventional analgesic therapies. Moreover, these patients also display increased cardiovascular responses to muscle contraction, which often leads to exercise intolerance or exacerbation of underlying cardiovascular conditions. This suggests that the mechanisms of myalgia development and the role of altered cardiovascular function under conditions of ischemia may be distinct compared to other injuries/diseases of the muscles. It is widely accepted that group III and IV muscle afferents play an important role in the development of pain due to ischemia. These same muscle afferents also form the sensory component of the exercise pressor reflex (EPR, which is the increase in heart rate and blood pressure (BP experienced after muscle contraction. Studies suggest that afferent sensitization after ischemia depends on interactions between purinergic (P2X and P2Y receptors, transient receptor potential (TRP channels, and acid sensing ion channels (ASICs in individual populations of peripheral sensory neurons. Specific alterations in primary afferent function through these receptor mechanisms correlate with increased pain related behaviors and altered EPRs. Recent evidence suggests that factors within the muscles during ischemic conditions including upregulation of growth factors and cytokines, and microvascular changes may be linked to the overexpression of these different receptor molecules in the dorsal root ganglia (DRG that in turn modulate pain and sympathetic reflexes. In this review article, we will discuss the

  9. Isotopic diagnosis of peripheral thrombosis

    International Nuclear Information System (INIS)

    Cornu, Pierre; Scalet, Michel

    1975-01-01

    Radio-isotope diagnosis of peripheral venous thrombosis, using tracer doses of iodine-labelled fibrinogen, provides an important contribution to the solution of the worrying problem of pulmonary embolism due to latent phlebitis. This elegant and precise technique permits early diagnosis of venous thrombosis of the lower limbs at a subclinical stage. It has permitted determination of the frequency, both after surgery and after myocardial infarction, and above all, it provides an objective criterion for assessment of the efficacy of prophylactic measures proposed [fr

  10. Transdermal optogenetic peripheral nerve stimulation

    Science.gov (United States)

    Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

    2017-06-01

    Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

  11. Diagnostic approach to peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Misra Usha

    2008-01-01

    Full Text Available Peripheral neuropathy refers to disorders of the peripheral nervous system. They have numerous causes and diverse presentations; hence, a systematic and logical approach is needed for cost-effective diagnosis, especially of treatable neuropathies. A detailed history of symptoms, family and occupational history should be obtained. General and systemic examinations provide valuable clues. Neurological examinations investigating sensory, motor and autonomic signs help to define the topography and nature of neuropathy. Large fiber neuropathy manifests with the loss of joint position and vibration sense and sensory ataxia, whereas small fiber neuropathy manifests with the impairment of pain, temperature and autonomic functions. Electrodiagnostic (EDx tests include sensory, motor nerve conduction, F response, H reflex and needle electromyography (EMG. EDx helps in documenting the extent of sensory motor deficits, categorizing demyelinating (prolonged terminal latency, slowing of nerve conduction velocity, dispersion and conduction block and axonal (marginal slowing of nerve conduction and small compound muscle or sensory action potential and dennervation on EMG. Uniform demyelinating features are suggestive of hereditary demyelination, whereas difference between nerves and segments of the same nerve favor acquired demyelination. Finally, neuropathy is classified into mononeuropathy commonly due to entrapment or trauma; mononeuropathy multiplex commonly due to leprosy and vasculitis; and polyneuropathy due to systemic, metabolic or toxic etiology. Laboratory investigations are carried out as indicated and specialized tests such as biochemical, immunological, genetic studies, cerebrospinal fluid (CSF examination and nerve biopsy are carried out in selected patients. Approximately 20% patients with neuropathy remain undiagnosed but the prognosis is not bad in them.

  12. Comparison of Allogeneic and Syngeneic Rat Glioma Models by Using MRI and Histopathologic Evaluation.

    Science.gov (United States)

    Biasibetti, Elena; Valazza, Alberto; Capucchio, Maria T; Annovazzi, Laura; Battaglia, Luigi; Chirio, Daniela; Gallarate, Marina; Mellai, Marta; Muntoni, Elisabetta; Peira, Elena; Riganti, Chiara; Schiffer, Davide; Panciani, Pierpaolo; Lanotte, Michele

    2017-03-01

    Research in neurooncology traditionally requires appropriate in vivo animal models, on which therapeutic strategies are tested before human trials are designed and proceed. Several reproducible animal experimental models, in which human physiologic conditions can be mimicked, are available for studying glioblastoma multiforme. In an ideal rat model, the tumor is of glial origin, grows in predictable and reproducible patterns, closely resembles human gliomas histopathologically, and is weakly or nonimmunogenic. In the current study, we used MRI and histopathologic evaluation to compare the most widely used allogeneic rat glioma model, C6-Wistar, with the F98-Fischer syngeneic rat glioma model in terms of percentage tumor growth or regression and growth rate. In vivo MRI demonstrated considerable variation in tumor volume and frequency between the 2 rat models despite the same stereotactic implantation technique. Faster and more reproducible glioma growth occurred in the immunoresponsive environment of the F98-Fischer model, because the immune response is minimized toward syngeneic cells. The marked inability of the C6-Wistar allogeneic system to generate a reproducible model and the episodes of spontaneous tumor regression with this system may have been due to the increased humoral and cellular immune responses after tumor implantation.

  13. Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

    Science.gov (United States)

    Epple-Farmer, Jessica; Debeb, Bisrat G.; Smithies, Oliver; Binas, Bert

    2012-01-01

    In view of the well-known phenomenon of trophoblast immune privilege, trophoblast stem cells (TSCs) might be expected to be immune privileged, which could be of interest for cell or gene therapies. Yet in the ectopic sites tested so far, TSC transplants fail to show noticeable immune privilege and seem to lack physiological support. However, we show here that after portal venous injection, green fluorescent protein (GFP)-labeled TSCs survive for several months in the livers of allogeneic female but not male mice. Gonadectomy experiments revealed that this survival does not require the presence of ovarian hormones but does require the absence of testicular factors. By contrast, GFP-labeled allogeneic embryonic stem cells (ESCs) are reliably rejected; however, these same ESCs survive when mixed with unlabeled TSCs. The protective effect does not require immunological compatibility between ESCs and TSCs. Tumors were not observed in animals with either successfully engrafted TSCs or coinjected ESCs. We conclude that in a suitable hormonal context and location, ectopic TSCs can exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as a new model for studying trophoblast immunology and physiology. PMID:19523327

  14. Hematopoietic stem cells from NOD mice exhibit autonomous behavior and a competitive advantage in allogeneic recipients.

    Science.gov (United States)

    Chilton, Paula M; Rezzoug, Francine; Ratajczak, Mariusz Z; Fugier-Vivier, Isabelle; Ratajczak, Janina; Kucia, Magda; Huang, Yiming; Tanner, Michael K; Ildstad, Suzanne T

    2005-03-01

    Type 1 diabetes is a systemic autoimmune disease that can be cured by transplantation of hematopoietic stem cells (HSCs) from disease-resistant donors. Nonobese diabetic (NOD) mice have a number of features that distinguish them as bone marrow transplant recipients that must be understood prior to the clinical application of chimerism to induce tolerance. In the present studies, we characterized NOD HSCs, comparing their engraftment characteristics to HSCs from disease-resistant strains. Strikingly, NOD HSCs are significantly enhanced in engraftment potential compared with HSCs from disease-resistant donors. Unlike HSCs from disease-resistant strains, they do not require graft-facilitating cells to engraft in allogeneic recipients. Additionally, they exhibit a competitive advantage when coadministered with increasing numbers of syngeneic HSCs, produce significantly more spleen colony-forming units (CFU-Ss) in vivo in allogeneic recipients, and more granulocyte macrophage-colony-forming units (CFU-GMs) in vitro compared with HSCs from disease-resistant controls. NOD HSCs also exhibit significantly enhanced chemotaxis to a stromal cell-derived factor 1 (SDF-1) gradient and adhere significantly better on primary stroma. This enhanced engraftment potential maps to the insulin-dependent diabetes locus 9 (Idd9) locus, and as such the tumor necrosis factor (TNF) receptor family as well as ski/sno genes may be involved in the mechanism underlying the autonomy of NOD HSCs. These findings may have important implications to understand the evolution of autoimmune disease and impact on potential strategies for cure.

  15. The fate of allogenic radiation sterilized bone grafts controlled by the electron spin resonance spectrometry

    International Nuclear Information System (INIS)

    Ostrowski, K.; Dziedzic-Goclawska, A.

    1981-01-01

    The normal fate of bone grafts is their resorption and substitution by the own host's bone tissue. This phenomenon described as creeping substitution process was controlled using biopsies from the grafted region in allogenic experimental system. Electron spin resonance (ESR) spectrometry was used for independent evaluation of resorption and substitution processes. The measurements were based on the process of induction in the hydroxyapatite (HA) crystals of bone mineral of stable paramagnetic centers which can be detected by ESR spectrometry. The loss of total amount of spins connected with the paramagnetic centers expressed in percent describes the kinetics of resorption. The changes in the concentration of spins due to the ''dilution'' of spins implanted with the graft by the nonirradiated ingrowing host's own bone describe the kinetics of the substitution process. Allogenic bone of calvaria was grafted orthotopically into rabbits after lyophilization and radiation sterilization with a dose of 3.5 Mrads. The process of graft's rebuilding was evaluated using the described ESR method. The application of the described technique in the human clinic is possible. (author)

  16. Durable responses to ibrutinib in patients with relapsed CLL after allogeneic stem cell transplantation.

    Science.gov (United States)

    Link, C S; Teipel, R; Heidenreich, F; Rücker-Braun, E; Schmiedgen, M; Reinhardt, J; Oelschlägel, U; von Bonin, M; Middeke, J M; Muetherig, A; Trautmann-Grill, K; Platzbecker, U; Bornhäuser, M; Schetelig, J

    2016-06-01

    Ibrutinib, a recently approved inhibitor of Bruton's tyrosine kinase (BTK), has shown great efficacy in patients with high-risk CLL. Nevertheless, there are few data regarding its use in patients who relapsed after allogeneic stem cell transplantation (alloSCT). We report clinical data from five CLL patients treated with ibrutinib for relapse after first or even second allogeneic transplantation. Additionally, we performed analyses on cytokine levels and direct measuring of CD4 Th1 and CD4 Th2 cells to evaluate possible clinically relevant immunomodulatory effects of ibrutinib. All patients achieved partial responses including one minimal residual disease (MRD)-negative remission. Within 1 year of follow-up, no relapse was observed. One patient died of severe pneumonia while on ibrutinib treatment. Beside this, no unexpected adverse events were observed. Flow cytometry and analyses of T cell-mediated cytokine levels (IL10 and TNFα) did not reveal substantial changes in T-cell distribution in favor of a CD4 Th1 T-cell shift in our patients. No acute exacerbation of GvHD was reported. In conclusion, these results support further evaluation of ibrutinib in CLL patients relapsing after alloSCT.

  17. Interactions of diffuse and focused allogenic recharge in an eogenetic karst aquifer (Florida, USA)

    Science.gov (United States)

    Langston, Abigail L.; Screaton, Elizabeth J.; Martin, Jonathan B.; Bailly-Comte, Vincent

    2012-06-01

    The karstic upper Floridan aquifer in north-central Florida (USA) is recharged by both diffuse and allogenic recharge. To understand how recharged water moves within the aquifer, water levels and specific conductivities were monitored and slug tests were conducted in wells installed in the aquifer surrounding the Santa Fe River Sink and Rise. Results indicate that diffuse recharge does not mix rapidly within the aquifer but instead flows horizontally. Stratification may be aided by the high matrix porosity of the eogenetic karst aquifer. Purging wells for sample collection perturbed conductivity for several days, reflecting mixing of the stratified water and rendering collection of representative samples difficult. Interpretive numerical simulations suggest that diffuse recharge impacts the intrusion of allogenic water from the conduit by increasing hydraulic head in the surrounding aquifer and thereby reducing influx to the aquifer from the conduit. In turn, the increase of head within the conduits affects flow paths of diffuse recharge by moving newly recharged water vertically as the water table rises and falls. This movement may result in a broad vertical zone of dissolution at the water table above the conduit system, with thinner and more focused water-table dissolution at greater distance from the conduit.

  18. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells.

    Science.gov (United States)

    Gornalusse, Germán G; Hirata, Roli K; Funk, Sarah E; Riolobos, Laura; Lopes, Vanda S; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G; Hanafi, Laïla-Aïcha; Clegg, Dennis O; Turtle, Cameron; Russell, David W

    2017-08-01

    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this 'missing-self' response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8 + T cells, do not bind anti-HLA antibodies and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression.

  19. HLA-E-expressing pluripotent stem cells escape allogeneic responses and lysis by NK cells

    Science.gov (United States)

    Gornalusse, Germán G.; Hirata, Roli K.; Funk, Sarah; Riolobos, Laura; Lopes, Vanda S.; Manske, Gabriel; Prunkard, Donna; Colunga, Aric G.; Hanafi, Laïla-Aïcha; Clegg, Dennis O.; Turtle, Cameron; Russell, David W.

    2017-01-01

    Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell (PSC)-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin (B2M) gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Here we show that this ‘missing self’ response can be prevented by forced expression of minimally polymorphic HLA-E molecules. We use adeno-associated virus (AAV)-mediated gene editing to knock in HLA-E genes at the B2M locus in human PSCs in a manner that confers inducible, regulated, surface expression of HLA-E single-chain dimers (fused to B2M) or trimers (fused to B2M and a peptide antigen), without surface expression of HLA-A, B or C. These HLA-engineered PSCs and their differentiated derivatives are not recognized as allogeneic by CD8+ T cells, do not bind anti-HLA antibodies, and are resistant to NK-mediated lysis. Our approach provides a potential source of universal donor cells for applications where the differentiated derivatives lack HLA class II expression. PMID:28504668

  20. Postoperative blood salvage versus allogeneic blood transfusion in total knee and hip arthroplasty: a literature review.

    Science.gov (United States)

    Leigheb, Massimiliano; Pogliacomi, Francesco; Bosetti, Michela; Boccafoschi, Francesca; Sabbatini, Maurizio; Cannas, Mario; Grassi, Federico

    2016-04-15

    We aimed to compare Postoperative Blood Salvage (PBS) with Allogeneic Blood Transfusion (ABT) in patients undergoing Total Hip and Knee Arthroplasty (THA, TKA).  A bibliographic research was carried out in order to review the literature dedicated to postoperative blood salvage in major orthopaedic surgery, excluding papers dealing exclusively with preoperative autologous donation, intraoperative blood salvage and ABT. PBS and ABT were compared according to complications, costs and duration of hospitalization. PBS effectiveness in reducing ABT was also assessed. PBS system is useful for reducing the complication rate and the length of hospital stay if compared to ABT. Costs for the reinfusion of unwashed shed blood, washed blood, and allogeneic transfusion are controversial among the different authors. Several papers demonstrate that PBS significantly reduces the need of postoperative ABT in both THA and TKA, while there is low evidence that PBS does not affect the risk of surgical wound complications. To reduce potential risks related to PBS, including non-hemolytic febrile reaction, the reinfusion of saved blood should begin within 4-6 hours after the start of collection through the wound drainage. According to literature, PBS appears to be a valid alternative to ABT, which is the standard treatment for postoperative anemia in THA and TKA. Contraindications to PBS must be ruled out before recommending it to patients undergoing major orthopaedic procedures.

  1. Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid Leukemia.

    Science.gov (United States)

    Elmariah, Hany; Pratz, Keith W

    2017-07-01

    Adult acute myeloid leukemia (AML) is often associated with a poor prognosis, with allogeneic transplantation representing the greatest chance of cure for eligible patients. Historically, the preferred donor source is a human leukocyte antigen-matched blood relative, although only approximately 30% of patients have access to such a donor. Alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical related donors, are available for almost every patient and are increasingly being used for patients without a matched related donor. Survival outcomes with these alternative donor sources now approximate those of matched related donor transplants. Given the safety and success of alternative donor transplants, comparative trials are needed to reassess the optimal donor source for patients with AML. This review summarizes the available data on these alternative donor transplants. Further investigation is needed to contemporize donor selection algorithms, but, in the current era, donor availability should no longer preclude a patient's eligibility for an allogeneic blood or marrow transplant. Copyright © 2017 by the National Comprehensive Cancer Network.

  2. Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Hensley, Michael Taylor; Tang, Junnan; Woodruff, Kathleen; Defrancesco, Teresa; Tou, Sandra; Williams, Christina M; Breen, Mathew; Meurs, Kathryn; Keene, Bruce; Cheng, Ke

    2017-08-01

    Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  3. Proliferation and Differentiation of Autologic and Allogenic Stem Cells in Supralethally X-Irradiated Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, I. L. [Department of Radiobiology, Central Institute of Haematology and Blood Transfusion, Moscow, USSR (Russian Federation)

    1967-07-15

    Full text: Allogenic bone marrow after transplantation into dogs irradiated with 1000 R X-rays differentiates in the normal way only for 3-4 days, afterwards transforming into lymphoid cells. This transformation is due to the antigen stimulus of the host on the grafted stem cells. The lymphoid cells, obtained from the host's blood on the 7-8th day after grafting, showed specific, immune activity under the Immune Lymphocyte Transfer test. Within a short duration of the immune response immunoblasts and immunocytes Undergo degenerative changes: destroyed mitochondria, formation of autophagic vacuoles and, finally, lysis of the cells. These changes are suggested to be the result of overloading of immune cells with antigen. Preliminary sensitization of the donor with prospective host's haemopoietic tissue does not hasten the immune transformation of haemopoiesis. Injections of bacterial pyrogen, cortisone or 6-mercaptopurine into recipients, as well as incubation of bone marrow at 37 Degree-Sign C for 2 hours, do not prevent the immune transformation. Preliminary thymectomy of the prospective recipients prevents in some of the cases immune transformation of the bone-marrow graft. The delay of allogenic bone-marrow transplantation for 5-6 days prevents in some dogs (X-irradiated with 1000 R, but not with 1200 R) the immune transformation. Transplantation of autologic bone marrow or shielding of the legs during irradiation is accompanied with good restoration of normal haemopoiesis without lymphoid transformation. (author)

  4. Avascular necrosis of bone following allogeneic hematopoietic cell transplantation in children and adolescents

    Science.gov (United States)

    Li, Xiaxin; Brazauskas, Ruta; Wang, Zhiwei; Al-Seraihy, Amal; Baker, K. Scott; Cahn, Jean-Yves; Frangoul, Haydar A.; Gajewski, James L.; Hale, Gregory A.; Hsu, Jack W.; Kamble, Rammurti T.; Lazarus, Hillard M.; Marks, David I.; Maziarz, Richard T.; Savani, Bipin N.; Shah, Ami J.; Shah, Nirali; Sorror, Mohamed L.; Wood, William A.; Majhail, Navneet S.

    2014-01-01

    We conducted a nested case-control study within a cohort of 6,244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents following allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States and had survived ≥ 6 months from transplantation. Overall, 160 cases with AVN and 478 controls matched by year of transplant, length of followup and transplant center were identified. Cases and controls were confirmed via central review of radiology, pathology and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared to patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with non-malignant diseases and those who had received reduced intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression post-HCT for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication. PMID:24388803

  5. Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: an Italian multicenter experience.

    Science.gov (United States)

    Faraci, Maura; Zecca, Marco; Pillon, Marta; Rovelli, Attilio; Menconi, Maria Cristina; Ripaldi, Mimmo; Fagioli, Franca; Rabusin, Marco; Ziino, Ottavio; Lanino, Edoardo; Locatelli, Franco; Daikeler, Thomas; Prete, Arcangelo

    2014-02-01

    Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  6. Association between thymic function and allogeneic hematopoietic stem cell transplantation outcome: results of a pediatric study.

    Science.gov (United States)

    Saglio, Francesco; Cena, Silvia; Berger, Massimo; Quarello, Paola; Boccasavia, Viola; Ferrando, Federica; Pittana, Laura; Bruno, Benedetto; Fagioli, Franca

    2015-06-01

    Robust T cell function recovery has been shown to be crucial in determining allogeneic hematopoietic stem cell transplantation (HSCT) outcome, and there is growing evidence that the thymus plays a central role in regulating this process. We performed a long-term analysis of the role of thymic activity recovery in a population of pediatric patients undergoing allogeneic HSCT by signal joint T cell receptor excision circle (sjTREC) quantification. In this study, characterized by a long-term follow-up (median, 72 months), we found patients with higher levels of sjTRECs before transplantation had a statistically significant reduced risk of death compared with patients with lower values (relative risk, .31; 95% confidence interval, .30 to .32; P = .02), showing this different outcome was mainly related to a reduction of relapse incidence (14% versus 43%, P = .02). Unlike previous reports, we observed no correlation between sjTREC levels and lymphocyte recovery. Moreover, we confirmed that only graft-versus-host disease influenced thymic activity after transplantation. In conclusion, our results suggest an association between pretransplantation thymic activity and the long-term outcome of pediatric patients undergoing HSCT, mainly through a reduction of relapse opportunities. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Eosinophils from hematopoietic stem cell recipients suppress allogeneic T cell proliferation.

    Science.gov (United States)

    Andersson, Jennie; Cromvik, Julia; Ingelsten, Madeleine; Lingblom, Christine; Andersson, Kerstin; Johansson, Jan-Erik; Wennerås, Christine

    2014-12-01

    Eosinophilia has been associated with less severe graft-versus-host disease (GVHD), but the underlying mechanism is unknown. We hypothesized that eosinophils diminish allogeneic T cell activation in patients with chronic GVHD. The capacity of eosinophils derived from healthy subjects and hematopoietic stem cell (HSC) transplant recipients, with or without chronic GVHD, to reduce allogeneic T cell proliferation was evaluated using a mixed leukocyte reaction. Eosinophil-mediated inhibition of proliferation was observed for the eosinophils of both healthy subjects and patients who underwent HSC transplantation. Eosinophils from patients with and without chronic GVHD were equally suppressive. Healthy eosinophils required cell-to-cell contact for their suppressive capacity, which was directed against CD4(+) T cells and CD8(+) T cells. Neither eosinophilic cationic protein, eosinophil-derived neurotoxin, indoleamine 2,3-dioxygenase, or increased numbers of regulatory T cells could account for the suppressive effect of healthy eosinophils. Real-time quantitative PCR analysis revealed significantly increased mRNA levels of the immunoregulatory protein galectin-10 in the eosinophils of both chronic GVHD patients and patients without GVHD, as compared with those from healthy subjects. The upregulation of galectin-10 expression in eosinophils from patients suggests a stimulatory effect of HSC transplantation in itself on eosinophilic galectin-10 expression, regardless of chronic GVHD status. To conclude, eosinophils from HSC transplant recipients and healthy subjects have a T cell suppressive capacity. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Intraoperative Ultrasound for Peripheral Nerve Applications.

    Science.gov (United States)

    Willsey, Matthew; Wilson, Thomas J; Henning, Phillip Troy; Yang, Lynda J-S

    2017-10-01

    Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Peripheral Vestibular System Disease in Vestibular Schwannomas

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

    2015-01-01

    density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas...... are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which...

  10. Peripheral refractive correction and automated perimetric profiles.

    Science.gov (United States)

    Wild, J M; Wood, J M; Crews, S J

    1988-06-01

    The effect of peripheral refractive error correction on the automated perimetric sensitivity profile was investigated on a sample of 10 clinically normal, experienced observers. Peripheral refractive error was determined at eccentricities of 0 degree, 20 degrees and 40 degrees along the temporal meridian of the right eye using the Canon Autoref R-1, an infra-red automated refractor, under the parametric conditions of the Octopus automated perimeter. Perimetric sensitivity was then undertaken at these eccentricities (stimulus sizes 0 and III) with and without the appropriate peripheral refractive correction using the Octopus 201 automated perimeter. Within the measurement limits of the experimental procedures employed, perimetric sensitivity was not influenced by peripheral refractive correction.

  11. Peripheral visual performance enhancement by neurofeedback training.

    Science.gov (United States)

    Nan, Wenya; Wan, Feng; Lou, Chin Ian; Vai, Mang I; Rosa, Agostinho

    2013-12-01

    Peripheral visual performance is an important ability for everyone, and a positive inter-individual correlation is found between the peripheral visual performance and the alpha amplitude during the performance test. This study investigated the effect of alpha neurofeedback training on the peripheral visual performance. A neurofeedback group of 13 subjects finished 20 sessions of alpha enhancement feedback within 20 days. The peripheral visual performance was assessed by a new dynamic peripheral visual test on the first and last training day. The results revealed that the neurofeedback group showed significant enhancement of the peripheral visual performance as well as the relative alpha amplitude during the peripheral visual test. It was not the case in the non-neurofeedback control group, which performed the tests within the same time frame as the neurofeedback group but without any training sessions. These findings suggest that alpha neurofeedback training was effective in improving peripheral visual performance. To the best of our knowledge, this is the first study to show evidence for performance improvement in peripheral vision via alpha neurofeedback training.

  12. Peripheral iridotomy for pigmentary glaucoma

    Science.gov (United States)

    Michelessi, Manuele; Lindsley, Kristina

    2016-01-01

    Background Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome. Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. Objectives The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. Search methods We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. Selection criteria We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. Data collection and analysis We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility

  13. Atherectomy for peripheral arterial disease.

    Science.gov (United States)

    Ambler, Graeme K; Radwan, Rami; Hayes, Paul D; Twine, Christopher P

    2014-03-17

    Symptomatic peripheral arterial disease may be treated by a number of options including exercise therapy, angioplasty, stenting and bypass surgery. Atherectomy is an alternative technique where atheroma is excised by a rotating cutting blade. The objective of this review was to analyse randomised controlled trials comparing atherectomy against any established treatment for peripheral arterial disease in order to evaluate the effectiveness of atherectomy. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). Trials databases were searched for details of ongoing or unpublished studies. Randomised controlled trials (RCTs) comparing atherectomy and other established treatments were selected for inclusion. All participants had symptomatic peripheral arterial disease with either claudication or critical limb ischaemia and evidence of lower limb arterial disease. Two review authors (GA and CT) screened studies for inclusion, extracted data and assessed the quality of the trials. Any disagreements were resolved through discussion. Four trials were included with a total of 220 participants (118 treated with atherectomy, 102 treated with balloon angioplasty) and 259 treated vessels (129 treated with atherectomy, 130 treated with balloon angioplasty). All studies compared atherectomy with angioplasty. No study was properly powered or assessors blinded to the procedures and there was a high risk of selection, attrition, detection and reporting biases.The estimated risk of success was similar between the treatment modalities although the confidence interval (CI) was compatible with small benefits of either treatment for the initial procedural success rate (Mantel-Haenszel risk ratio (RR) 0.92, 95% CI 0.44 to 1.91, P = 0.82), patency at six months (Mantel-Haenszel RR 0.92, 95% CI 0.51 to 1.66, P = 0.79) and patency at 12 months (Mantel-Haenszel RR 1.17, 95% CI 0

  14. Contrast-enhanced peripheral MRA

    DEFF Research Database (Denmark)

    Nielsen, Yousef W; Thomsen, Henrik S

    2012-01-01

    MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic......-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged...... intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal...

  15. Taxane-Induced Peripheral Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Roser Velasco

    2015-04-01

    Full Text Available Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment. Among them, paclitaxel and docetaxel are most commonly administered, but newer formulations are being investigated. Taxane antineoplastic activity is mainly based on the ability of the drugs to promote microtubule assembly, leading to mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the major non-hematological adverse effect of taxane, often manifested as painful neuropathy experienced during treatment, and it is sometimes irreversible. Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the initiation of treatment. The present review aims to dissect current knowledge on real incidence, underlying pathophysiology, clinical features and predisposing factors related with the development of taxane-induced neuropathy.

  16. Outcomes of allogeneic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria with or without aplastic anemia.

    Science.gov (United States)

    Lee, Sung-Eun; Park, Sung Soo; Jeon, Young-Woo; Yoon, Jae-Ho; Cho, Byung-Sik; Eom, Ki-Sung; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Kim, Hee-Je; Cho, Seok-Goo; Kim, Dong-Wook; Min, Woo-Sung; Lee, Jong Wook

    2017-10-01

    The aim of this study was to evaluate the long-term outcomes of allogeneic stem cell transplantation (SCT) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with or without aplastic anemia (AA). A total of 33 patients with PNH clones who underwent allogeneic SCT were analyzed. After a median follow-up of 57 months (range, 6.0-151.3), the 5-year estimated overall survival rate was 87.9±5.7%. Four patients died of transplant-related mortality (TRM). With the exception of one patient with early TRM, 32 patients were engrafted. Two patients who had developed delayed GF received a second transplant and recovered. The cumulative incidences of acute graft-vs-host disease (GVHD) (≥grade II) and chronic GVHD (≥moderate) were 27.3±7.9% and 18.7±7.0%, respectively. Twenty-one patients receiving SCT with reduced-intensity conditioning (RIC) had available follow-up data for PNH cell population for the first 6 months post-transplant. Analysis of these data revealed that the PNH clones disappeared within approximately 2 months. RIC regimen was sufficient to eradicate PNH clones with sustained donor-type engraftment after allogeneic SCT. Therefore, application of allogeneic SCT with RIC should be considered in patients with PNH, in accordance with the severity of the underlying bone marrow failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Perioperative allogenic blood transfusion is a poor prognostic factor after hepatocellular carcinoma surgery: a multi-center analysis.

    Science.gov (United States)

    Wada, Hiroshi; Eguchi, Hidetoshi; Nagano, Hiroaki; Kubo, Shoji; Nakai, Takuya; Kaibori, Masaki; Hayashi, Michihiro; Takemura, Shigekazu; Tanaka, Shogo; Nakata, Yasuyuki; Matsui, Kosuke; Ishizaki, Morihiko; Hirokawa, Fumitoshi; Komeda, Koji; Uchiyama, Kazuhisa; Kon, Masanori; Doki, Yuichiro; Mori, Masaki

    2018-01-01

    The influence of allogenic blood transfusion on the postoperative outcomes of hepatocellular carcinoma (HCC) surgery remains controversial. This study aims to clarify the clinical impacts of perioperative allogenic blood transfusion on liver resection outcome in HCC patients. We analyzed data collected over 5 years for 642 patients who underwent hepatectomy for HCC at one of the five university hospitals. We investigated the impact of allogenic blood transfusion on postoperative outcome after surgery in all patients and in 74 matched pairs, using a propensity score. Of the 642 patients, 198 (30.8%) received perioperative allogenic blood transfusion (AT group) and 444 (69.2%) did not (non-AT group). Overall survival was lower in the AT group than in the non-AT group in univariate (P blood transfusion was found to be a poor prognostic factor for HCC patients. In this multi-center study, perioperative blood transfusion was an independent factor for poor prognosis after curative surgery for primary HCC in the patient group and in pairs matched by propensity scores.

  18. Correction of lysosomal enzyme deficiency in various organs of beta-glucuronidase-deficient mice by allogeneic bone marrow transplantation

    NARCIS (Netherlands)

    Hoogerbrugge, P. M.; Poorthuis, B. J.; Mulder, A. H.; Wagemaker, G.; Dooren, L. J.; Vossen, J. M.; van Bekkum, D. W.

    1987-01-01

    The correction of lysosomal enzyme deficiency was investigated for various organs of beta-glucuronidase-deficient C3H/Rij mice after allogeneic bone marrow transplantation from an enzymatically normal donor strain (C57BL/Rij). In the hemopoietic organs, the enzyme level increased to levels found in

  19. Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

    Directory of Open Access Journals (Sweden)

    Paul Lohan

    2017-11-01

    Full Text Available Mesenchymal stromal cells (MSC have been used to treat a broad range of disease indications such as acute and chronic inflammatory disorders, autoimmune diseases, and transplant rejection due to their potent immunosuppressive/anti-inflammatory properties. The breadth of their usage is due in no small part to the vast quantity of published studies showing their ability to modulate multiple immune cell types of both the innate and adaptive immune response. While patient-derived (autologous MSC may be the safer choice in terms of avoiding unwanted immune responses, factors including donor comorbidities may preclude these cells from use. In these situations, allogeneic MSC derived from genetically unrelated individuals must be used. While allogeneic MSC were initially believed to be immune-privileged, substantial evidence now exists to prove otherwise with multiple studies documenting specific cellular and humoral immune responses against donor antigens following administration of these cells. In this article, we will review recent published studies using non-manipulated, inflammatory molecule-activated (licensed and differentiated allogeneic MSC, as well as MSC extracellular vesicles focusing on the immune responses to these cells and whether or not such responses have an impact on allogeneic MSC-mediated safety and efficacy.

  20. Ex Vivo Oncolytic Virotherapy with Myxoma Virus Arms Multiple Allogeneic Bone Marrow Transplant Leukocytes to Enhance Graft versus Tumor

    NARCIS (Netherlands)

    Lilly, Cameron L.; Villa, Nancy Y.; Lemos de Matos, Ana; Ali, Haider M.; Dhillon, Jess-Karan S.; Hofland, Tom; Rahman, Masmudur M.; Chan, Winnie; Bogen, Bjarne; Cogle, Christopher; McFadden, Grant

    2017-01-01

    Allogeneic stem cell transplant-derived T cells have the potential to seek and eliminate sites of residual cancer that escaped primary therapy. Oncolytic myxoma virus (MYXV) exhibits potent anti-cancer efficacy against human cancers like multiple myeloma (MM) and can arm transplant-derived T cells

  1. In vitro evaluation of allogeneic bone screws for use in internal fixation of transverse fractures created in proximal sesamoid bones obtained from equine cadavers.

    Science.gov (United States)

    Sasaki, Naoki; Takakuwa, Jun; Yamada, Haruo; Mori, Ryuji

    2010-04-01

    To evaluate effectiveness of allogeneic bone screws and pins for internal fixation of midbody transverse fractures of equine proximal sesamoid bones (PSBs) in vitro. 14 forelimbs from cadavers of 3-year-old Thoroughbreds. Allogeneic cortical bone fragments were collected from the limbs of a male Thoroughbred, and cortical bone screws were prepared from the tissue by use of a precision desktop microlathe programmed with the dimensions of a metal cortical bone screw. A midbody transverse osteotomy of each PSB was performed by use of a bone-shaping oscillating saw and repaired via 1 of 3 internal fixation techniques: 1 allogeneic bone screw with 1 allogeneic bone pin (type I; n = 6 PSBs), 2 allogeneic bone screws (type II; 8), or 1 stainless steel cortical bone screw (control repair; 6). Mechanical tension measurements were obtained by use of a commercially available materials testing system. Mean +/- SD tensile strength (TS) was 668.3 +/- 216.6 N for type I repairs, 854.4 +/- 253.2 N for type II repairs, and 1,150.0 +/- 451.7 N for control repairs. Internal fixation of PSB fractures by the use of allogeneic bone screws and bone pins was successful. Although mean TS of control repairs with stainless steel cortical bone screws was greater than the mean TS of type I and type II repairs, the difference between type II and control repairs was not significant. Allogeneic screws may advance healing and result in fewer complications in a clinical setting.

  2. Peripheral Developing Odontoma or Peripheral Ameloblastic Fibroodontoma: A Rare Challenging Case

    Directory of Open Access Journals (Sweden)

    Saede Atarbashi Moghadam

    2016-01-01

    Full Text Available Peripheral odontogenic lesions are considered to be rare within the classification of odontogenic tumors. They share the same microscopic characteristics of their central counterparts. Here, we report an ulcerated mass of the maxillary gingiva that on histopathological examination was diagnosed as peripheral developing odontoma or peripheral ameloblastic fibroodontoma. The diagnosis of this tumor is challenging and may lead to unnecessary treatment.

  3. Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

    Science.gov (United States)

    Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; Chun, Tae-Wook; Rhame, Frank; Baker, Jason V; Busch, Michael P; Chomont, Nicolas; Dean, Patrick G; Fromentin, Rémi; Haase, Ashley T; Hampton, Dylan; Keating, Sheila M; Lada, Steven M; Lee, Tzong-Hae; Natesampillai, Sekar; Richman, Douglas D; Schacker, Timothy W; Wietgrefe, Stephen; Yu, Xu G; Yao, Joseph D; Zeuli, John; Lichterfeld, Mathias; Badley, Andrew D

    2017-11-01

    Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

  4. Short- and long-term follow-up of thyroid dysfunction after allogeneic bone marrow transplantation without the use of preparative total body irradiation.

    Science.gov (United States)

    Toubert, M E; Socié, G; Gluckman, E; Aractingi, S; Espérou, H; Devergie, A; Ribaud, P; Parquet, N; Schlageter, M H; Beressi, J P; Rain, J D; Vexiau, P

    1997-08-01

    We studied the incidence and potential prognostic value of thyroid abnormalities after allogeneic bone marrow transplantation (BMT) without total body irradiation (TBI) conditioning. 77 consecutive patients who received a chemotherapy-alone-based conditioning regimen pretransplant were included. Free serum thyroxine (FT4), free serum triiodothyronine (FT3) and serum thyrotropin (TSH) levels were assayed before and 3 and 14 months after BMT. Patients were classified in three categories: normal thyroid profile if FT3 and FT4 were within the normal range and TSH was normal or low, peripheral thyroid insufficiency (PTI) if TSH was >4 mIU/l, or an 'euthyroid sick syndrome' (ETS) if FT3 and/or FT4 were low and TSH was normal or low. The incidence of thyroid dysfunction at 3 months was 57%, and 29% at 14 months. This was mostly due to the occurrence of ETS which was more frequent at 3 months (48%, 29/61) than at 14 months (19%, 9/48). Furthermore, at 3 months, survival was significantly lower in the ETS group (34.5%) than in the euthyroid group (96.2%), or in the PTI group (83.3%) (P < 0.0001). PTI was observed even in the absence of TBI in 11 patients (14%) and was equally distributed at 3 months (n = 6) and 14 months (n = 5). In conclusion, thyroid dysfunction is not a rare complication even without pretransplant TBI conditioning regimen. Hypothyroidism prevalence was 10%, and ETS, which was more frequently observed, displayed a dismal predictive value at 3 months.

  5. Imaging of the peripheral vascular system

    International Nuclear Information System (INIS)

    Gould, S.A.; Pond, G.D.; Pinsky, S.; Moss, G.S.; Srikantaswamy, S.; Ryo, U.Y.

    1984-01-01

    This book is limited neither to the peripheral vascular system nor to diagnostic imaging techniques. Its 18 chapters cover nonimaging blood-flow techniques (Doppler ultrasound, plethysmography) as well as noninvasive and invasive imaging techniques (ultrasound, computed tomography, radionuclide digital-subtraction angiography, and contrast angiography). These are applied not only to the peripheral vascular system but also to the aorta and vena cava

  6. Beauty and cuteness in peripheral vision

    Science.gov (United States)

    Kuraguchi, Kana; Ashida, Hiroshi

    2015-01-01

    Guo et al. (2011) showed that attractiveness was detectable in peripheral vision. Since there are different types of attractiveness (Rhodes, 2006), we investigated how beauty and cuteness are detected in peripheral vision with a brief presentation. Participants (n = 45) observed two Japanese female faces for 100 ms, then were asked to respond which face was more beautiful (or cuter). The results indicated that both beauty and cuteness were detectable in peripheral vision, but not in the same manner. Discrimination rates for judging beauty were invariant in peripheral and central vision, while discrimination rates for judging cuteness declined in peripheral vision as compared with central vision. This was not explained by lower resolution in peripheral vision. In addition, for male participants, it was more difficult to judge cuteness than beauty in peripheral vision, thus suggesting that gender differences can have a certain effect when judging cuteness. Therefore, central vision might be suitable for judging cuteness while judging beauty might not be affected by either central or peripheral vision. This might be related with the functional difference between beauty and cuteness. PMID:25999883

  7. Late taste disorders in bone marrow transplantation: clinical evaluation with taste solutions in autologous and allogeneic bone marrow recipients.

    Science.gov (United States)

    Marinone, M G; Rizzoni, D; Ferremi, P; Rossi, G; Izzi, T; Brusotti, C

    1991-01-01

    The aim of this work was to determine the type and the significance of taste disorders in allogeneic bone marrow transplanted patients. In a retrospective study the taste threshold of a cohort of 15 allogeneic bone marrow transplanted patients, 4-51 months after transplantation (mean: 30.6 +/- 15.8), was compared to the taste threshold of 8 autologous bone marrow recipients, 4-48 months after transplantation (mean: 24.12 +/- 12.18), and to the taste threshold of a group of 20 consecutive normal subjects. Allogeneic bone marrow transplanted patients showed a significant hypogeusia for salt (Pearson's chi square p = 0.0002; Yates' correction p = 0.0007) and sour (Pearson's chi square p = 0.001; Yates' correction p = 0.008). No significant variations were observed for sweet and bitter. Autologous bone marrow recipients did not show any significant variation of taste acuity for sweet, salt or sour; a constant reduction of the taste threshold for bitter was observed, but the values were not significantly different from normal (Pearson's chi square p = 0.47; Yates' correction p = 0.83). So, late and selective taste disorders are observed in allogeneic bone marrow transplanted patients. Since the severity of the disorders is not strictly related to the severity of chronic oral G.V.H.D., taste analysis could discover the slightest, clinically undetectable cases of chronic oral G.V.H.D. The mechanism of immune aggression on the sensorial taste cells is poorly understood. Further trials are needed to define variations of taste acuity not only after allogeneic bone marrow transplantation, but also in systemic immune diseases.

  8. Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera.

    Science.gov (United States)

    Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J

    2017-06-01

    Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

    Science.gov (United States)

    Weinger, Jason G; Plaisted, Warren C; Maciejewski, Sonia M; Lanier, Lewis L; Walsh, Craig M; Lane, Thomas E

    2014-10-01

    Transplantation of major histocompatibility complex-mismatched mouse neural precursor cells (NPCs) into mice persistently infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in rapid rejection that is mediated, in part, by T cells. However, the contribution of the innate immune response to allograft rejection in a model of viral-induced neurological disease has not been well defined. Herein, we demonstrate that the natural killer (NK) cell-expressing-activating receptor NKG2D participates in transplanted allogeneic NPC rejection in mice persistently infected with JHMV. Cultured NPCs derived from C57BL/6 (H-2(b) ) mice express the NKG2D ligand retinoic acid early precursor transcript (RAE)-1 but expression was dramatically reduced upon differentiation into either glia or neurons. RAE-1(+) NPCs were susceptible to NK cell-mediated killing whereas RAE-1(-) cells were resistant to lysis. Transplantation of C57BL/6-derived NPCs into JHMV-infected BALB/c (H-2(d) ) mice resulted in infiltration of NKG2D(+) CD49b(+) NK cells and treatment with blocking antibody specific for NKG2D increased survival of allogeneic NPCs. Furthermore, transplantation of differentiated RAE-1(-) allogeneic NPCs into JHMV-infected BALB/c mice resulted in enhanced survival, highlighting a role for the NKG2D/RAE-1 signaling axis in allograft rejection. We also demonstrate that transplantation of allogeneic NPCs into JHMV-infected mice resulted in infection of the transplanted cells suggesting that these cells may be targets for infection. Viral infection of cultured cells increased RAE-1 expression, resulting in enhanced NK cell-mediated killing through NKG2D recognition. Collectively, these results show that in a viral-induced demyelination model, NK cells contribute to rejection of allogeneic NPCs through an NKG2D signaling pathway. © 2014 AlphaMed Press.

  10. Efficacy of tranexamic acid in reducing allogeneic blood products in adolescent idiopathic scoliosis surgery.

    Science.gov (United States)

    Sui, Wen-yuan; Ye, Fang; Yang, Jun-lin

    2016-04-27

    Adolescent idiopathic scoliosis (AIS) surgery usually require prolonged operative times with extensive soft tissue dissection and significant perioperative blood loss, and allogeneic blood products are frequently needed. Methods to reduce the requirement for transfusion would have a beneficial effect on these patients. Although many previous studies have revealed the efficacy of tranexamic acid (TXA) in spinal surgery, there is still a lack of agreement concerning the reduction of both blood loss and transfusion requirements of large dose tranexamic acid (TXA) in surgery for adolescent idiopathic scoliosis (AIS). The objective of this study was to elevate the efficacy and safety of a large dose tranexamic acid (TXA) in reducing transfusion requirements of allogeneic blood products in adolescent idiopathic scoliosis (AIS) surgery using a retrospective study designed with historical control group. One hundred thirty seven consecutive AIS patients who underwent surgery treatment with posterior spinal pedicle systems from August 2011 to March 2015 in our scoliosis center were retrospectively reviewed. Patients were divided into two groups, the TXA group and the historical recruited no TXA group (NTXA). Preoperative demographics, radiographic parameters, operative parameters, estimated blood loss (EBL), total irrigation fluid, number of patients requiring blood transfusion, mean drop of Hb (Pre-op Hb-Post-op Hb), haematocrit pre and post-surgery, mean volume of blood transfusion, hospitalization time, and adverse effect were recorded and compared. All the patients were successfully treated with satisfied clinical and radiographic outcomes. There were 71 patients in the TXA group and 66 patients in the NTXA group. The preoperative demographics were homogeneity between two groups (P > 0.05). There were no significant difference in average operative time between two groups (209 min vs 215 min, p >0.05). Number of patients in the TXA group showed a significant decrease in

  11. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    International Nuclear Information System (INIS)

    Dhollander, A.A.M.; Huysse, W.C.J.; Verdonk, P.C.M.; Verstraete, K.L.; Verdonk, R.; Verbruggen, G.; Almqvist, K.F.

    2010-01-01

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  12. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Dhollander, A.A.M., E-mail: Aad.Dhollander@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Huysse, W.C.J., E-mail: Wouter.Huysse@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, P.C.M., E-mail: pverdonk@yahoo.co [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verstraete, K.L., E-mail: Koenraad.Verstraete@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, R., E-mail: Rene.Verdonk@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verbruggen, G., E-mail: Gust.Verbruggen@Ugent.b [Laboratory of Connective Tissue Biology, Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Almqvist, K.F., E-mail: Fredrik.Almqvist@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium)

    2010-07-15

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  13. Peripherally applied opioids for postoperative pain

    DEFF Research Database (Denmark)

    Nielsen, B N; Henneberg, S W; Schmiegelow, K

    2015-01-01

    BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June...... 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity...... difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved...

  14. Transplante de células-tronco epiteliais límbicas alógenas expandidas ex vivo sobre membrana amniótica: relato de caso Transplantation of allogenic limbal epithelial stem cells cultivated ex vivo on amniotic membrane: case report

    Directory of Open Access Journals (Sweden)

    José Álvaro Pereira Gomes

    2009-04-01

    Full Text Available Paciente apresentou falência de transplante de limbo e conjuntiva de doador vivo alógeno no olho direito após ceratoconjuntivite epidêmica. Após alguns meses, foi submetida a transplante de células-tronco epiteliais límbicas alógenas cultivadas ex vivo sobre membrana amniótica (primeiro caso no Brasil, tendo evoluído com epitelização total da córnea e melhora da acuidade visual. Após o 3º mês da cirurgia, iniciou-se neovascularização superficial periférica com piora da transparência corneana. A visão manteve-se 0,1 após um ano de cirurgia.Case report of a patient who developed failure of an allogenic living related conjunctival limbal transplantation in the right eye after an episode of epidemic keratoconjunctivitis. After a few months, she underwent transplantation of allogenic limbal epithelial stem cells cultivated ex vivo on amniotic membrane (first case in Brazil. The patient evolved with total corneal epithelialization and improvement of the visual acuity. Three months after the surgery, peripheral superficial neovascularization with worsening of the corneal transparency was observed. The vision remained 0.1 after one year of the transplantation.

  15. A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

    2007-01-01

    Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

  16. Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors

    International Nuclear Information System (INIS)

    Sato, Tatsusuke; Suga, Michio; Kudo, Hajime; Waga, Takashi; Ogasawara, Masamichi

    1980-01-01

    Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (Tetraploid type, 10 5 cells) after repeated immunization with gamma-irradiated (13,000 rads 60 Co) allogeneic non-viral tumors of ascites type (Tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation. (author)

  17. Allogeneic Hematopoietic Cell Transplantation for Dyskeratosis Congenita: A Report of 3 Cases.

    Science.gov (United States)

    Tamura, Shinichi; Imamura, Toshihiko; Urata, Takayo; Kobayashi, Miki; Gen, Mari; Tomii, Toshihiro; Do, Junko; Osone, Shinya; Ishida, Hiroyuki; Hosoi, Hajime; Kuroda, Hiroshi

    2017-10-01

    Although bone marrow failure in patients with dyskeratosis congenita (DKC) can be successfully treated with allogeneic hematopoietic cell transplantation (allo-HCT) using a reduced intensity conditioning (RIC) regimen, the outcome of nonhematological disorders in patients with DKC treated with allo-HCT using RIC has not been fully elucidated. Here, we describe the clinical course of nonhematological disorders after allo-HCT with RIC in 3 consecutive patients with DKC. Allo-HCT with RIC was feasible in all cases; however, patient 1 developed lethal pulmonary disease and patient 2 experienced progression of hepatic fibrosis. Careful follow-up of patient-specific complications is required after allo-HCT in patients with DKC.

  18. Co-Culturing of Multipotent Mesenchymal Stromal Cells with Autological and Allogenic Lymphocytes.

    Science.gov (United States)

    Kapranov, N M; Davydova, Yu O; Gal'tseva, I V; Petinati, N A; Bakshinskaitė, M V; Drize, N I; Kuz'mina, L A; Parovichnikova, E N; Savchenko, V G

    2018-03-01

    We studied the effect of autologous and allogeneic lymphocytes on multipotent mesenchymal stromal cells in co-culture. It is shown that changes in multipotent mesenchymal stromal cells and in lymphocytes did not depend on the source of lymphocytes. Contact with lymphocytes triggers expression of HLA-DR molecules on multipotent mesenchymal stromal cells and these cells lose their immune privilege. In multipotent mesenchymal stromal cells, the relative level of expression of factors involved in immunomodulation (IDO1, PTGES, and IL-6) and expression of adhesion molecule ICAM1 increased, while expression of genes involved in the differentiation of multipotent mesenchymal stromal cells remained unchanged. Priming of multipotent mesenchymal stromal cells with IFN did not affect these changes. In turn, lymphocytes underwent activation, expression of HLA-DR increased, subpopulation composition of lymphocytes changed towards the increase in the content of naïve T cells. These findings are important for cell therapy.

  19. Process change evaluation framework for allogeneic cell therapies: impact on drug development and commercialization.

    Science.gov (United States)

    Hassan, Sally; Huang, Hsini; Warren, Kim; Mahdavi, Behzad; Smith, David; Jong, Simcha; Farid, Suzanne S

    2016-04-01

    Some allogeneic cell therapies requiring a high dose of cells for large indication groups demand a change in cell expansion technology, from planar units to microcarriers in single-use bioreactors for the market phase. The aim was to model the optimal timing for making this change. A development lifecycle cash flow framework was created to examine the implications of process changes to microcarrier cultures at different stages of a cell therapy's lifecycle. The analysis performed under assumptions used in the framework predicted that making this switch earlier in development is optimal from a total expected out-of-pocket cost perspective. From a risk-adjusted net present value view, switching at Phase I is economically competitive but a post-approval switch can offer the highest risk-adjusted net present value as the cost of switching is offset by initial market penetration with planar technologies. The framework can facilitate early decision-making during process development.

  20. [Perioperative management of Jehovah's Witness patients. Special consideration of religiously motivated refusal of allogeneic blood transfusion].

    Science.gov (United States)

    Habler, O; Voss, B

    2010-04-01

    The religious organization of Jehovah's Witnesses numbers more than 7 million members worldwide, including 165,000 members in Germany. Although Jehovah's Witnesses strictly refuse the transfusion of allogeneic red blood cells, platelets and plasma, Jehovah's Witness patients may nevertheless benefit from modern therapeutic concepts including major surgical procedures without facing an excessive risk of death. The present review describes the perioperative management of surgical Jehovah's Witness patients aiming to prevent fatal anemia and coagulopathy. The cornerstones of this concept are 1) education of the patient about blood conservation techniques generally accepted by Jehovah's Witnesses, 2) preoperative optimization of the cardiopulmonary status and correction of preoperative anemia and coagulopathy, 3) perioperative collection of autologous blood, 4) minimization of perioperative blood loss and 5) utilization of the organism's natural anemia tolerance and its acute accentuation in the case of life-threatening anemia.

  1. Where does allogeneic stem cell transplantation fit in the treatment of chronic lymphocytic leukemia?

    Science.gov (United States)

    Dreger, Peter; Montserrat, Emili

    2015-03-01

    Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been considered as the treatment of choice for patients with high-risk chronic lymphocytic leukemia (CLL) (i.e., refractory to purine analogs, short response (CLL treatment armamentarium. These signal transduction inhibitors (STI) will change the algorithms of high-risk CLL (HR-CLL) management. Despite the limited body of evidence, there is sufficient rationale for withholding alloHSCT in patients with 17p-/TP53mut CLL in first remission. In contrast, the perspectives of patients with relapsed 17p-/TP53mut CLL remain uncertain even if responding to STI. The same accounts for patients with HR-CLL progressing under STI. In both scenarios, it is reasonable to consider alloHSCT, ideally after response to alternative STI regimens.

  2. Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

    Science.gov (United States)

    Khouri, I F; Sui, D; Jabbour, E J; Samuels, B I; Turturro, F; Alatrash, G; Anderlini, P; Ahmed, S; Oran, B; Ciurea, S O; Marin, D; Olson, A; Patel, K K; Popat, U R; Ledesma, C; Kadia, T M; Ferrajoli, A; Burger, J A; Jorgensen, J L; Medeiros, L J; Bassett, R L; Gulbis, A M

    2017-01-01

    Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

  3. Acute Fibrinous and Organizing Pneumonia Associated With Allogenic Hematopoietic Stem Cell Transplant Successfully Treated With Corticosteroids

    Directory of Open Access Journals (Sweden)

    Lam-Phuong Nguyen DO

    2016-04-01

    Full Text Available Acute fibrinous and organizing pneumonia (AFOP is an extremely rare, relatively new, and distinct histological pattern of acute lung injury characterized predominately by the presence of intra-alveolar fibrin and associated organizing pneumonia. AFOP may be idiopathic or associated with a wide spectrum of clinical conditions. It has a variable clinical presentation from mild respiratory symptoms to that similar to the acute respiratory distress syndrome. Currently there is no consensus on treatment, and corticosteroids previously were of unclear benefit. To date, there are less than 40 cases of AFOP reported in the literature and only one has been linked to hematopoietic stem cell transplantation. Here we report the first case series of 2 patients who developed AFOP following allogenic stem cell transplant that were successfully treated with high-dose corticosteroids.

  4. Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

    DEFF Research Database (Denmark)

    Pedersen, Alma B; Mehnert, Frank; Overgaard, Søren

    2009-01-01

    BACKGROUND: Allogeneic red blood cell transfusion is frequently used in total hip replacement surgery (THR). However, data on the prognosis of transfused patients are sparse. In this study we compared the risk of complications following THR in transfused and non-transfused patients. METHODS......: A population-based follow-up study was performed using data from medical databases in Denmark. We identified 28,087 primary THR procedures performed from 1999 to 2007, from which we computed a propensity score for red blood cell transfusion based on detailed data on patient-, procedure-, and hospital......-related characteristics. We were able to match 2,254 transfused with 2,254 non-transfused THR patients using the propensity score. RESULTS: Of the 28,087 THR patients, 9,063 (32.3%) received at least one red blood cell transfusion within 8 days of surgery. Transfused patients had higher 90-day mortality compared...

  5. The impact of allogenic blood transfusion on the outcomes of total pancreatectomy with islet autotransplantation.

    Science.gov (United States)

    Yoshimatsu, Gumpei; Shahbazov, Rauf; Saracino, Giovanna; Lawrence, Michael C; Kim, Peter T; Onaca, Nicholas; Beecherl, Ernest E; Naziruddin, Bashoo; Levy, Marlon F

    2017-11-01

    Allogenic blood transfusion (ABT) may be needed for severe bleeding during total pancreatectomy with autotransplantation (TPIAT), but may induce inflammation. This study investigated the impact of ABT. With a population of 83 patients who underwent TPIAT from 2006 to 2014, this study compared cytokine levels, patient characteristics, islet characteristics, metabolic outcomes, insulin requirements, and hemoglobin A1c for those who received a blood transfusion (BT) versus no blood transfusion (NBT). Initially, proinflammatory cytokines were moderately higher in the BT group than the NBT group. Despite longer procedures and more severe bleeding, the BT group had similar values to the NBT group for insulin requirements, serum C-peptide, hemoglobin A1c, and insulin independence rate. The probability of insulin independence was slightly higher in patients receiving ≥3 units of blood. ABT induced elevation of proinflammatory cytokines during the perioperative period in TPIAT, but these changes did not significantly change posttransplant islet function. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Inhibition of IL-1 activity induced with allogeneic transfusion of UV-irradiated blood

    International Nuclear Information System (INIS)

    Horvat, B.; Poljak-Blazi, M.; Hadija, M.

    1991-01-01

    Treatment with UV-irradiated donor-specific blood transfusion is known to induce specific unresponsiveness in recipient animals and prolong allograft survival. Mixed lymphocyte response in transfused mice was decreased towards spleen cells of the blood donor strain, but was not altered to third-party cells. Sera from treated mice showed significantly lower interleukin-1 (IL-1) activity, which was increased with higher dilutions of sera, indicating the presence of IL-1 inhibitor. Furthermore, sera decreased rIL-1-induced cell proliferation in dose-dependent manner, while the response to rIL-2 neither depended on the concentration of sera, nor differed between non-treated controls and treated mice. These results indicate that UV-irradiated allogeneic blood transfusion could induce an inhibitor, specifically directed to IL-1 activity, which may be involved in the generation of immunological unresponsiveness in treated animals. (author)

  7. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

    Science.gov (United States)

    Carson, Jeffrey L; Carless, Paul A; Hebert, Paul C

    2012-04-18

    Most clinical practice guidelines recommend restrictive red cell transfusion practices, with the goal of minimising exposure to allogeneic blood. The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). To examine the evidence for the effect of transfusion thresholds on the use of allogeneic and/or autologous red cell transfusion, and the evidence for any effect on clinical outcomes. We identified trials by searching; The Cochrane Injuries Group Specialised Register (searched 01 Feb 2011), Cochrane Central Register of Controlled Trials 2011, issue 1 (The Cochrane Library), MEDLINE (Ovid) 1948 to January Week 3 2011, EMBASE (Ovid) 1980 to 2011 (Week 04), ISI Web of Science: Science Citation Index Expanded (1970 to Feb 2011), ISI Web of Science: Conference Proceedings Citation Index- Science (1990 to Feb 2011). We checked reference lists of other published reviews and relevant papers to identify any additional trials. Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered. Risk ratios of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials, using a random effects model. Data extraction and assessment of the risk of bias was performed by two people. Nineteen trials involving a total of 6264 patients were identified, and were similar enough that the results could be combined. Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39% (RR 0.61, 95% CI 0.52 to 0.72). This equates to an average absolute risk reduction (ARR) of 34% (95% CI 24% to 45%). The volume of RBCs transfused was reduced on average by 1

  8. Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat

    International Nuclear Information System (INIS)

    Tanaka, S.; Sakai, A.

    1979-01-01

    The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulatng capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3 H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude

  9. Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Karlsson, Lene; Forestier, Erik; Hasle, Henrik

    2017-01-01

    Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children...... relapsed. The influence of disease characteristics, first line treatment, relapse therapy and duration of first remission on outcome was analysed. Second complete remission (CR2) was achieved in 146 (70%) patients. Estimated 5-year overall survival (OS5y ) was 39 ± 4% for the whole group and 43 ± 4......, no allogeneic stem cell transplantation (SCT) in first remission and core binding factor AML were independent favourable prognostic factors for survival. For the 128 children (124 in CR2) that received SCT as consolidation therapy after relapse, OS5y was 61 ± 5%. Four of 19 children (21%) survived without...

  10. Prognosis of Allogeneic Haematopoietic Stem Cell Recipients Admitted to the Intensive Care Unit

    DEFF Research Database (Denmark)

    Lindgaard, Sidsel Christy; Nielsen, Jonas; Lindmark, Anders

    2016-01-01

    BACKGROUND: Allogeneic haematopoietic stem cell transplantation (HSCT) is a procedure with inherent complications and intensive care may be necessary. We evaluated the short- and long-term outcomes of the HSCT recipients requiring admission to the intensive care unit (ICU). METHODS: We...... ventilation had a statistically significant effect on in-ICU (p = 0.02), 6-month (p = 0.049) and 1-year (p = 0.014) mortality. Renal replacement therapy also had a statistically significant effect on in-hospital (p = 0.038) and 6-month (p = 0.026) mortality. Short ICU admissions, i.e. ... to the ICU was confirmed in our study. Mechanical ventilation, renal replacement therapy and an ICU admission of ≥10 days were each risk factors for mortality in the first year after ICU admission....

  11. Successful allogeneic stem cells transplantation in severe aplastic anaemia complicated by dengue fever

    International Nuclear Information System (INIS)

    Ullah, K.; Satti, T.M.; Ahmed, P.; Raza, A.; Akhtar, F.M.; Tariq, W.U.Z.

    2007-01-01

    Aplastic anaemia is characterized by severe compromise of haematopoiesis and hypocellular bone marrow. Haemorrhagic episodes in patients with aplastic anemia occur usually secondary to thrombocytopenia and require frequent support with platelet concentrates and other blood products. Infection with dengue virus (particularly dengue sero type-2 of South Asian genotype) is associated with dengue haemorrhagic fever. Dengue infection further worsens the disease process in patients with aplastic anaemia due to uncontrolled haemorrhagic diathesis and major organ failure, which may prove fatal in these already immunocompromised patients, if not treated in time. Recent epidemics of dengue haemorrhagic fever has not only affected the southern region of our country but also spread to other areas of the country. With this background, we report a case of aplastic anaemia complicated by dengue haemorrhagic fever who achieved successful engraftment after allogeneic stem cell transplantation from sibling brother and is having normal healthy post transplant life. (author)

  12. Homing regularity of different doses bone marrow transplantation in allogeneic hosts

    International Nuclear Information System (INIS)

    Sun Suping; Cai Jianming; Xiang Yingsong; Zhao Fang; Huang Dingde; Gao Jianguo; Yang Rujun

    2001-01-01

    Objective: To explore the homing regularity of different doses of bone marrow cell transplantation. Method: An allogeneic mouse model was used. The homing status of different dose groups from the first day to the forth day after transplantation were observed. Results: The rate of positive cells in bone marrow and spleen: differences among four groups was not significant. The rate of positive cells of third day was highest among four days (P<0.01). A phenomenon that homing-mobilization-re-homing could be observed. The homing efficiency: low dose groups were higher than that high dose groups (P<0.01). Conclusion: The homing efficiency of low dose groups is higher than that of the high dose groups in certain range, the routine method of transplanting a large quantities cells by a single injection may be an waste

  13. Late Mortality and Causes of Death among Long-Term Survivors after Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Atsuta, Yoshiko; Hirakawa, Akihiro; Nakasone, Hideki; Kurosawa, Saiko; Oshima, Kumi; Sakai, Rika; Ohashi, Kazuteru; Takahashi, Satoshi; Mori, Takehiko; Ozawa, Yukiyasu; Fukuda, Takahiro; Kanamori, Heiwa; Morishima, Yasuo; Kato, Koji; Yabe, Hiromasa; Sakamaki, Hisashi; Taniguchi, Shuichi; Yamashita, Takuya

    2016-09-01

    We sought to assess the late mortality risks and causes of death among long-term survivors of allogeneic hematopoietic stem cell transplantation (HCT). The cases of 11,047 relapse-free survivors of a first HCT at least 2 years after HCT were analyzed. Standardized mortality ratios (SMR) were calculated and specific causes of death were compared with those of the Japanese population. Among relapse-free survivors at 2 years, overall survival percentages at 10 and 15 years were 87% and 83%, respectively. The overall risk of mortality was significantly higher compared with that of the general population. The risk of mortality was significantly higher from infection (SMR = 57.0), new hematologic malignancies (SMR = 2.2), other new malignancies (SMR = 3.0), respiratory causes (SMR = 109.3), gastrointestinal causes (SMR = 3.8), liver dysfunction (SMR = 6.1), genitourinary dysfunction (SMR = 17.6), and external or accidental causes (SMR = 2.3). The overall annual mortality rate showed a steep decrease from 2 to 5 years after HCT; however, the decrease rate slowed after 10 years but was still higher than that of the general population at 20 years after HCT. SMRs in the earlier period of 2 to 4 years after HCT and 5 years or longer after HCT were 16.1 and 7.4, respectively. Long-term survivors after allogeneic HCT are at higher risk of mortality from various causes other than the underlying disease that led to HCT. Screening and preventive measures should be given a central role in reducing the morbidity and mortality of HCT recipients on long-term follow-up. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. The ability of natural tolerance to be applied to allogeneic tissue: determinants and limits

    Directory of Open Access Journals (Sweden)

    Razavy Haide

    2007-04-01

    Full Text Available Abstract Background Transplant rejection has been considered to occur primarily because donor antigens are not present during the development of the recipient's immune system to induce tolerance. Thus, transplantation prior to recipient immune system development (pre-immunocompetence transplants should induce natural tolerance to the donor. Surprisingly, tolerance was often not the outcome in such 'natural tolerance models'. We explored the ability of natural tolerance to prevent immune responses to alloantigens, and the reasons for the disparate outcomes of pre-immunocompetence transplants. Results We found that internal transplants mismatched for a single minor-H antigen and 'healed-in' before immune system development were not ignored but instead induced natural tolerance. In contrast, multiple minor-H or MHC mismatched transplants did not consistently induce natural tolerance unless they carried chimerism generating passenger lymphocytes. To determine whether the systemic nature of passenger lymphocytes was required for their tolerizing capacity, we generated a model of localized vs. systemic donor lymphocytes. We identified the peritoneal cavity as a site that protects allogeneic lymphocytes from killing by NK cells, and found that systemic chimerism, but not chimerism restricted to the peritoneum, was capable of generating natural tolerance. Conclusion These data provide an explanation for the variable results with pre-immunocompetence transplants and suggest that natural tolerance to transplants is governed by the systemic vs. localized nature of donor antigen, the site of transplantation, and the antigenic disparity. Furthermore, in the absence of systemic lymphocyte chimerism the capacity to establish natural tolerance to allogeneic tissue appears strikingly limited. Reviewers This article was reviewed by Matthias von Herrath, Irun Cohen, and Wei-Ping Min (nominated by David Scott.

  15. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.

    1977-01-01

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  16. Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies.

    Science.gov (United States)

    Simaria, Ana S; Hassan, Sally; Varadaraju, Hemanthram; Rowley, Jon; Warren, Kim; Vanek, Philip; Farid, Suzanne S

    2014-01-01

    For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 10(9) cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway. © 2013 Wiley Periodicals, Inc.

  17. Iodoacetate and allogenous cartilage particles as models for arthritis induction in equine

    Directory of Open Access Journals (Sweden)

    Ahmed Elmesiry

    2014-12-01

    Full Text Available Experimental models of osteoarthritis (OA have been widely developed in different animal species, because of the high incidence of osteoarthritis diseases in humans and animals. To date, no ideal OA animal model has been reported. The present study compare different osteoarthritis models to determine which one is suitable for inducing experimental equine OA. Fifteen donkeys were divided into three equal groups (n = 5. The radio carpal joints of the right forelimb of 15 donkeys were injected with 25 mg monoiodoacetate (MIA (group A, 50 mg allogenous cartilage particles (ACP (group B, or vehicle solution (group C over a period of 70 days. Osteoarthritis induction was evaluated weekly through lameness score, carpal circumference, joint flexion angel, synovial fluid analysis (total protein and WBC count, and radiology. Animal were euthanized and joints histopathology were performed at 70 days. Lameness score and joint circumference was increased in both group A and B however joint flexion angel was decreased compared to group C (p < 0.05. Osteophytes were observed in MIA injected joints only accompanied with subchondral bone sclerosis. Cartilage damage was observed grossly and histologically in Group A together with synovial membrane fibrosis. Group B had on cartilage damage grossly however histological examination revealed some cartilage surface discontinuity with synovial membrane edema. Injection of monoiodoacetate in the donkey is a successful model to create the acute clinical signs of joint disease as well as cartilage damage. However, allogenous cartilage particles injection need more investigation to be applied.

  18. Allogeneic hematopoietic stem cell transplantation in Primary Cutaneous T Cell Lymphoma.

    Science.gov (United States)

    Cudillo, Laura; Cerretti, Raffaella; Picardi, Alessandra; Mariotti, Benedetta; De Angelis, Gottardo; Cantonetti, Maria; Postorino, Massimiliano; Ceresoli, Eleonora; De Santis, Giovanna; Nasso, Daniela; Pisani, Francesco; Scala, Enrico; Di Piazza, Fabio; Lanti, Alessandro

    2018-06-01

    In our retrospective study, 16 patients affected by advanced cutaneous T cell lymphoma (CTCL) underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two patients (12.5%) were in complete remission (CR), nine (56.3%) in partial remission (PR), and five (31.2%) with active disease. The patients were transplanted from an HLA-identical (n = 7) from a mismatched (n = 1) or haploidentical (n = 1) sibling, from matched unrelated donor (n = 5), or from a single cord blood unit (n = 2). Conditioning regimen was standard myeloablative in 6 patients and at reduced intensity in 10. Seven patients died from non relapse mortality (NRM) and four patients relapsed or progressed, three of them achieved a second CR after donor lymphocyte infusion (DLI) or chemotherapy plus DLI. To date, with a median follow-up of 76 months (range 6-130), nine patients are alive, eight in CR, and one with active disease. Overall survival (OS) and disease-free survival (DFS) at 1 and 10 years are 61% (95% CI 40-91%) and 54% (95% CI 33-86%), 40% (95% CI 22-74%), and 34% (95% CI 16-68%), respectively. The time from diagnosis to transplant seems to influence negatively both OS (log-rank p < 0.04) and DFS (log-rank p < 0.05). Our results confirm on a long follow-up that CTCL appears particularly susceptible to the graft versus lymphoma (GVL) effect, so that allogeneic HSCT represents a possibility of cure for advanced CTCL. The timing of HSCT in the clinical course of disease remains an open issue.

  19. Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents.

    Science.gov (United States)

    Li, Xiaxin; Brazauskas, Ruta; Wang, Zhiwei; Al-Seraihy, Amal; Baker, K Scott; Cahn, Jean-Yves; Frangoul, Haydar A; Gajewski, James L; Hale, Gregory A; Hsu, Jack W; Kamble, Rammurti T; Lazarus, Hillard M; Marks, David I; Maziarz, Richard T; Savani, Bipin N; Shah, Ami J; Shah, Nirali; Sorror, Mohamed L; Wood, William A; Majhail, Navneet S

    2014-04-01

    We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived ≥ 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  20. Posaconazole plasma exposure correlated to intestinal mucositis in allogeneic stem cell transplant patients.

    Science.gov (United States)

    Vanstraelen, Kim; Prattes, Juergen; Maertens, Johan; Lagrou, Katrien; Schoemans, Hélène; Peersman, Nele; Vermeersch, Pieter; Theunissen, Koen; Mols, Raf; Augustijns, Patrick; Annaert, Pieter; Hoenigl, Martin; Spriet, Isabel

    2016-08-01

    Low posaconazole plasma concentrations (PPCs) are frequently encountered in allogeneic hematopoietic stem cell transplant (HSCT) patients, due to variable gastrointestinal absorption. In this study, the impact of intestinal mucositis on posaconazole exposure is investigated. A prospective pharmacokinetic study was performed including allogeneic HSCT patients receiving posaconazole prophylaxis with the oral suspension or tablets. Steady state PPCs were determined using high-performance liquid chromatography-fluorescence detection at the day of transplantation (=day 0), day +7, and +14. Citrulline was measured using liquid chromatography-tandem mass spectrometry to evaluate severity of mucositis, at baseline (day -7 or -6), and at day 0, +7 and +14. Additionally, citrulline plasma concentrations and steady state trough PPCs were determined in hematological patients without HSCT or mucositis. Thirty-four HSCT patients received posaconazole oral suspension together with 25 cL of Coca Cola, 6 HSCT patients received posaconazole tablets and 33 hematological patients not receiving HSCT received posaconazole oral suspension. The median (interquartile range) average PPC was 0.26 mg/L (0.17-0.43), 0.67 mg/L (0.27-1.38), and 1.08 mg/L (0.96-1.38), with suspension in HSCT patients, suspension in hematological patients and tablets in HSCT patients, respectively. A higher trough PPC was encountered with the oral suspension when citrulline plasma concentrations were above 10 μmol/L compared to values below 10 μmol/L (p < 0.001), whereas for tablets, average PPCs remained high with citrulline plasma concentrations below or above 10 μmol/L (p = 0.64). Posaconazole tablets should be preferred to suspension in HSCT patients immediately after transplantation to prevent insufficient plasma exposure due to intestinal mucositis.

  1. Changes in the expression of FGFR3 in patients with chronic myeloid leukaemia receiving transplants of allogeneic peripheral blood stem cells

    Czech Academy of Sciences Publication Activity Database

    Dvořáková, D.; Krejčí, P.; Mayer, J.; Fajkus, Jiří; Hampl, Aleš; Dvořák, Petr

    2001-01-01

    Roč. 113, č. 3 (2001), s. 832-835 ISSN 0007-1048 R&D Projects: GA ČR GA312/97/0393; GA MŠk ME 198 Institutional research plan: CEZ:AV0Z5045916 Keywords : fibroblast growth factor receptor 3 * chronic myeloid leukaemia * stem cell transplantation Subject RIV: BO - Biophysics Impact factor: 2.815, year: 2001

  2. Ionic mechanisms in peripheral pain.

    Science.gov (United States)

    Fransén, Erik

    2014-01-01

    Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs. © 2014 Elsevier Inc. All rights reserved.

  3. Peripheral Blood stem cell transplantation in children with Beta-thalassemia major

    International Nuclear Information System (INIS)

    Farzana, T.; Shamsi, T.S.; Irfan, M.; Ansari, S.H.; Baig, M.I.; Shakoor, N.

    2003-01-01

    Objective: To share the preliminary data on stem cell transplantation in Pakistan. Results: Engraftment was achieved in all patients except one who required a second dose of bone marrow graft on day +21. Median time to achieve absolute neutrophil count of > 0.5 x 10/sup 9/ /l was 9.0 days (range 8 - 31 days) and platelet count of > 20 x 10/sup 9/ /l was 14 days (12 - 35 days). Acute GVHD was seen in 3 patients, one patient had grade IV gut GVHD; another patient had grade III gut GVHD while third patient had grade II skin GVHD. Median hospital stay was 29 days. Six patients were well and transfusion independent 3 to 36 months post transplant. One episode of primary graft failure required a second dose of bone marrow harvest. Another episode of graft rejection received two doses of donor lymphocytes infusion. There were 4 deaths due to grade IV gut GVHD because of uncontrolled systemic Candida infection and one due to hepatic veno-occlusive (VOD) disease. Conclusion: Allogeneic peripheral blood stem cell transplantation can be safely and economically carried out in Pakistan. Although there had been 4 deaths during 36 months follow-up, with increasing understanding and experience the outcome is expected to improve. (author)

  4. Differential induction from X-irradiated human peripheral blood monocytes to dendritic cells

    International Nuclear Information System (INIS)

    Yoshino, Hironori; Takahashi, Kenji; Monzen, Satoru; Kashiwakura, Ikuo

    2008-01-01

    Dendritic cells (DCs) are a type of antigen-presenting cell which plays an essential role in the immune system. To clarify the influences of ionizing radiation on the differentiation to DCs, we focused on human peripheral blood monocytes and investigated whether X-irradiated monocytes can differentiate into DCs. The non-irradiated monocytes and 5 Gy-irradiated monocytes were induced into immature DCs (iDCs) and mature DCs (mDCs) with appropriate cytokine stimulation, and the induced cells from each monocyte expressed each DC-expressing surface antigen such as CD40, CD86 and HLA-DR. However, the expression levels of CD40 and CD86 on the iDCs derived from the 5 Gy-irradiated monocytes were higher than those of iDCs derived from non-irradiated monocytes. Furthermore, the mDCs derived from 5 Gy-irradiated monocytes had significantly less ability to stimulate allogeneic T cells in comparison to the mDCs derived from non-irradiated monocytes. There were no significant differences in the phagocytotic activity of the iDCs and cytokines detected in the supernatants conditioned by the DCs from the non-irradiated and irradiated monocytes. These results suggest that human monocytes which are exposed to ionizing radiation can thus differentiate into DCs, but there is a tendency that X-irradiation leads to an impairment of the function of DCs. (author)

  5. In vitro X-ray irradiation of human peripheral blood T lymphocytes enhances suppressor function

    International Nuclear Information System (INIS)

    Ogawa, H.; Tsunematsu, T.

    1983-01-01

    The effect of in vitro X-ray irradiation on human peripheral blood T lymphocytes was studied with regard to their suppressor activity related to the concanavalin A (Con A)-induced suppressor system. To generate suppressor T lymphocytes, purified human T lymphocytes were incubated for 3 days in the first culture, with or without Con A. These lymphocytes were irradiated with various doses of X-ray before, mid or after the culture. After doing a second culture for 6 days, the suppressive influence of these cells on T lymphocyte proliferation rates stimulated with allogeneic mononuclear cells, and B lymphocyte proliferation rates stimulated with pokeweed mitogen was measured. Irradiation of cultures to which Con A had not been added induced much the same level of suppressor activity as seen in the cultures with Con A. The suppressor activity gradually increased with time from the irradiation to the suppressor cell assay. Suppressor T lymphocytes were resistant to X-ray irradiation and independent of DNA synthesis. However, irradiation-induced enhancement was minimal in cultures incubated with con A, regardless of the irradiation time. (author)

  6. Cognate CD4 T-cell licensing of dendritic cells heralds anti-CMV CD8 T-cell immunity after human allogeneic umbilical cord blood transplantation

    NARCIS (Netherlands)

    Flinsenberg, T W H; Spel, Lotte; Jansen, M; Koning, D; de Haar, C; Plantinga, M; Scholman, R; van Loenen, M M; Nierkens, S; Boon, L; van Baarle, D; Heemskerk, M H M; Boelens, J J; Boes, M

    2014-01-01

    Reactivation of human cytomegalovirus (CMV) is hazardous to patients undergoing allogeneic cord-blood transplantation (CBT), lowering survival rates by approximately 25%. While antiviral treatment ameliorates viremia, complete viral control requires CD8(+) T-cell-driven immunity. Mouse studies

  7. Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fiona C. Lewis, BSc, PhD

    2017-12-01

    Full Text Available Skeletal muscle-derived PW1pos/Pax7neg interstitial cells (PICs express and secrete a multitude of proregenerative growth factors and cytokines. Utilizing a porcine preclinical skeletal muscle injury model, delivery of allogeneic porcine PICs (pPICs significantly improved and accelerated myofiber regeneration and neocapillarization, compared with saline vehicle control-treated muscles. Allogeneic pPICs did not contribute to new myofibers or capillaries and were eliminated by the host immune system. In conclusion, allogeneic pPIC transplantation stimulated the endogenous stem cell pool to bring about enhanced autologous skeletal muscle repair and regeneration. This allogeneic cell approach is considered a cost-effective, easy to apply, and readily available regenerative therapeutic strategy.

  8. Immunodeficiency after allogeneic bone marrow transplantation in man. Effect of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187) in vitro

    DEFF Research Database (Denmark)

    Møller, J; Hofmann, B; Langhoff, E

    1989-01-01

    This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found...

  9. Peripheral cemento-ossifying fibroma of maxilla.

    Science.gov (United States)

    Chatterjee, Anirban; Ajmera, Neha; Singh, Amit

    2010-07-01

    Peripheral cemento-ossifying fibroma is a reactive gingival overgrowth occurring frequently in anterior maxilla. It is a slow-growing benign tumor which may lead to pathologic migration and other periodontal problems, so it should be excised as soon as possible. The recurrence rate of peripheral cemento-ossifying fibroma is reported to be 8% to 20%, so a close postoperative follow-up is required. Herein, we are reporting a similar case of peripheral cemento-ossifying fibroma in the maxillary anterior region.

  10. CT characteristics of peripheral organizing pneumonia

    International Nuclear Information System (INIS)

    Yang, Seong Oh; Choi, Chul Soon; Kim, Myung Joon; Lee, Kyung Soo; Choi, Hyung Sik; Jun, Young Hwan; Park, Yong Koo

    1988-01-01

    Diagnostic dilemma of persistent mass-forming parenchymal opacity in the lung periphery occurs occasionally in the realm of diagnostic radiology. Until recently, literature on the role of computed tomography in peripheral organizing pneumonia, which is difficult to differentiate from malignancy, has little been published. We experienced one case of pathologically proven organizing pneumonia diagnosed preoperatively by chest CT. When it comes to solitary peripheral mass density in the lung, we think that CT can be proved useful in the diagnosis of benign organizing pneumonia by showing regular and smoothly corrugate margin, peripheral contrast enhancement with inner low density, and air-trapping by intervening normal lung parenchyma.

  11. Peripheral facial nerve dysfunction: CT evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Disbro, M.A.; Harnsberger, H.R.; Osborn, A.G.

    1985-06-01

    Peripheral facial nerve dysfunction may have a clinically apparent or occult cause. The authors reviewed the clinical and radiographic records of 36 patients with peripheral facial nerve dysfunction to obtain information on the location of the suspected lesion and the number, sequence, and type of radiographic evaluations performed. Inadequate clinical evaluations before computed tomography (CT) was done and unnecessary CT examinations were also noted. They have suggested a practical clinical and radiographic scheme to evaluate progressive peripheral facial dysfunction with no apparent cause. If this scheme is applied, unnecessary radiologic tests and delays in diagnosis and treatment may be avoided.

  12. Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

    International Nuclear Information System (INIS)

    Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L.

    1991-01-01

    Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days

  13. The role of HLA antibodies in allogeneic SCT: is the 'type-and-screen' strategy necessary not only for blood type but also for HLA?

    Science.gov (United States)

    Yoshihara, S; Taniguchi, K; Ogawa, H; Saji, H

    2012-12-01

    The role of HLA antibodies in SCT has drawn increasing attention because of the significantly increased number of patients who receive HLA-mismatched SCT, including cord blood transplantation, haploidentical SCT and unrelated SCT. Technical advancements in the methods of HLA Ab testing have realized rapid, accurate and objective identification, as well as quantification of specific HLA antibodies. Recent clinical studies have suggested that the presence of donor-specific HLA antibodies (DSA) in patients is associated with graft failure in HLA-mismatched SCT when the above-listed stem cell sources are used and results in different impacts. Of note, most of the 'HLA-matched' unrelated SCT actually involve HLA mismatches in HLA-DP and the presence of antibodies against this locus has been reported to be associated with graft failure. Thus, HLA Ab should be examined as a work-up for all patients who undergo SCT from 'alternative donors.' The simplest route for preventing HLA Ab-mediated graft failure in Ab-positive patients is to avoid donors who possess the target Ag of HLA antibodies. If SCT from such donors must be performed, treatment for DSA before SCT may improve the chances of successful donor engraftment.

  14. Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Morling, N

    1988-01-01

    .01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data...... monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c...

  15. Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

    International Nuclear Information System (INIS)

    Massenkeil, G.; Zschieschang, P.; Thiel, G.; Hemmati, P. G.; Budach, V.; Dörken, B.; Pross, J.; Arnold, R.

    2015-01-01

    Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

  16. АВ0-INCOMPATIBILITY IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: 15-YEARS EXPERIENCE OF R.M. GORBACHEVA MEMORIAL RESEARCH INSTITUTE FOR CHILDREN ONCOLOGY, HEMATOLOGY AND TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. A. Kucher

    2016-01-01

    Full Text Available Introduction. AB0-incompatibility in different types of allogeneic hematopoietic stem cell transplantation (HSCT may be an additional aggravating factor for the development of immunological complications and decrease treatment efficacy.Materials and methods. From May 1999 to December 2015 in R.M. Gorbacheva Memorial Research Institute for Children Oncology, Hematology and Transplantation 1131 patients with malignancies and hereditary diseases were included to the study, which were performed 1428 allogeneic HSCT: allogeneic unrelated – 814 (57.0 %, allogeneic related – 344 (24.1 %, haploidentical – 267 (18.7 %, umbilical cord blood in 3 patients (0.2 %. Age was 0–76 years, median – 25 years.Results. In 54.6 % of cases (n = 780 АВ0-incompatibility was determined: major – 37.8 % (n = 295; minor – 45.4 % (n = 354; combined – 16.8 % (n = 131. АВ0-incompatibility in allogeneic HSCT did not influence overall survival (p = 0.56, frequency of acute graftversus-host disease (GVHD (p = 0.2. There was an increased frequency of acute GVHD in combination with reduced intensity conditioning regimens and АВ0-incompatibility (30.8 % compared with myeloablative regimens (15.3 %; p = 0.002.Conclusion. The presence of АВ0-incompatibility is not a limiting factor to perform allogeneic HSCT, however, it demands high quality prophylaxis and sophisticated transfusion therapy to prevent immune complications.

  17. EDITORIAL MODERN TECHNOLOGY IN PERIPHERAL HEALTH ...

    African Journals Online (AJOL)

    hi-tech

    2004-06-01

    Jun 1, 2004 ... new technology to peripheral health care systems in developing countries. ... and maintenance of medical equipment in Africa, citing information ... operating laboratory equipment, and for emergency lighting for operating ...

  18. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  19. Side Effects: Nerve Problems (Peripheral Neuropathy)

    Science.gov (United States)

    Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

  20. Angioplasty and stent placement - peripheral arteries

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007393.htm Angioplasty and stent placement - peripheral arteries To use the sharing features ... inside the arteries and block blood flow. A stent is a small, metal mesh tube that keeps ...

  1. Peripheral myelin protein 22 alters membrane architecture

    Science.gov (United States)

    Mittendorf, Kathleen F.; Marinko, Justin T.; Hampton, Cheri M.; Ke, Zunlong; Hadziselimovic, Arina; Schlebach, Jonathan P.; Law, Cheryl L.; Li, Jun; Wright, Elizabeth R.; Sanders, Charles R.; Ohi, Melanie D.

    2017-01-01

    Peripheral myelin protein 22 (PMP22) is highly expressed in myelinating Schwann cells of the peripheral nervous system. PMP22 genetic alterations cause the most common forms of Charcot-Marie-Tooth disease (CMTD), which is characterized by severe dysmyelination in the peripheral nerves. However, the functions of PMP22 in Schwann cell membranes remain unclear. We demonstrate that reconstitution of purified PMP22 into lipid vesicles results in the formation of compressed and cylindrically wrapped protein-lipid vesicles that share common organizational traits with compact myelin of peripheral nerves in vivo. The formation of these myelin-like assemblies depends on the lipid-to-PMP22 ratio, as well as on the PMP22 extracellular loops. Formation of the myelin-like assemblies is disrupted by a CMTD-causing mutation. This study provides both a biochemical assay for PMP22 function and evidence that PMP22 directly contributes to membrane organization in compact myelin. PMID:28695207

  2. Peripheral Arterial Disease Can Be a Killer

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Special Section Peripheral Arterial Disease Can Be a Killer Past Issues / ... Color changes in skin, paleness, or blueness Lower temperature in one leg compared to the other leg ...

  3. Management of peripheral facial nerve palsy

    OpenAIRE

    Finsterer, Josef

    2008-01-01

    Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell?s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the...

  4. Atherectomy in Peripheral Artery Disease: A Review.

    Science.gov (United States)

    Bhat, Tariq M; Afari, Maxwell E; Garcia, Lawrence A

    2017-04-01

    Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.

  5. Passive Scalar Evolution in Peripheral Region

    OpenAIRE

    Lebedev, V. V.; Turitsyn, K. S.

    2003-01-01

    We consider evolution of a passive scalar (concentration of pollutants or temperature) in a chaotic (turbulent) flow. A universal asymptotic behavior of the passive scalar decay (homogenization) related to peripheral regions (near walls) is established. The passive scalar moments and its pair correlation function in the peripheral region are analyzed. A special case investigated in our paper is the passive scalar decay along a pipe.

  6. Peripheral Circulatory Features during High-Frequency Jet Ventilation

    Directory of Open Access Journals (Sweden)

    M. B. Kontorovich

    2010-01-01

    Full Text Available The paper gives the results of a study of peripheral circulatory features during high-frequency jet ventilation (HFJV. The main specific features of peripheral circulation and oxygen transport during HFJV are formulated on the basis of a study of cardiac output (impedance cardiography, peripheral vascular resistance, peripheral vascular blood filling (photoplethysmogram analysis, adaptive peripheral blood flow reactions (spectral analysis of peripheral vascular pulsation. HFJV gives rise to the peculiar pattern of peripheral hemodynamics and tissue gas exchange, which is characterized by higher oxygen uptake without a decrease in mixed venous blood saturation, with normal extraction coefficient and preserved low peripheral vascular resistance. During HFJV, unlike traditional ventilation, the main peripheral hemodynamic feature is the increased capillary bed blood volume caused by the blood flow involvement of reserve capillaries under control of volume (parasympathetic regulation of adaptive peripheral hemodynamic reactions. Key words: high-frequency jet ventilation, oxygen transport, peripheral hemodynamics.

  7. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia

    DEFF Research Database (Denmark)

    Craddock, Charles; Labopin, Myriam; Robin, Marie

    2016-01-01

    Disease relapse is the most common cause of treatment failure after allogeneic stem cell transplantation for acute myeloid leukemia and myelodysplastic syndromes, yet treatment options for such patients remain extremely limited. Azacitidine is an important new therapy in high-risk myelodysplastic...... syndromes and acute myeloid leukemia but its role in patients who relapse post allograft has not been defined. We studied the tolerability and activity of azacitidine in 181 patients who relapsed after an allograft for acute myeloid leukemia (n=116) or myelodysplastic syndromes (n=65). Sixty-nine patients...... conclude that azacitidine represents an important new therapy in selected patients with acute myeloid leukemia/myelodysplastic syndromes who relapse after allogeneic stem cell transplantation. Prospective studies to confirm optimal treatment options in this challenging patient population are required....

  8. The effect of in vitro irradiation on the responses of human lymphocytes to PHA, PPD and allogeneic cells

    International Nuclear Information System (INIS)

    Herva, E.; Kiviniitty, K.; Oulu Univ.

    1975-01-01

    The effect of X-ray, cobalt and 45 MeV electron irradiation on the responses of lymphocytes to PHA, PPD and allogeneic cells was studied using a semimicro lymphocyte culture technique. The responses to PPD and allogeneic cells were found to be more sensitive to irradiation than the response to PHA, even when the time factor was taken into account, i.e. the effect of irradiation was measured on the same day irrespective the type os stimulation. At the doses used, 500, 3,000 and 6,000 rd, there was no difference between the effects of the three types of radiation used. The possible explanations for the findings are discussed. (orig.) [de

  9. The Basel experience with total body irradiation for conditioning patients with acute leukemia for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    Speck, B.; Cornu, P.; Nissen, C.; Gratwohl, A.; Sartorius, J.

    1979-01-01

    We are reporting our experience with 13 patients suffering from end stage acute leukemia that were prepared for allogeneic bone marrow transplantation by combined chemotherapy followed by high dose cyclophosphamide (Cy) and total body irradiation (TBI). Only one patient became a long term survivor. Of the evaluable 12 patients, 6 died of interstitial pneumonia, 4 of GvH and 1 of recurrent leukemia. We conclude that adding combined chemotherapy to the standard conditioning program with Cy and TBI probably increases the risk of developing fatal interstitial pneumonia without eliminating the risk of recurrent leukemia. We suggest that allogenic marrow grafts should be performed earlier in the course of refractory acute leukemias, because in patients with end stage disease its chances of being curative are small

  10. Mini-review: Far peripheral vision.

    Science.gov (United States)

    Simpson, Michael J

    2017-11-01

    The region of far peripheral vision, beyond 60 degrees of visual angle, is important to the evaluation of peripheral dark shadows (negative dysphotopsia) seen by some intraocular lens (IOL) patients. Theoretical calculations show that the limited diameter of an IOL affects ray paths at large angles, leading to a dimming of the main image for small pupils, and to peripheral illumination by light bypassing the IOL for larger pupils. These effects are rarely bothersome, and cataract surgery is highly successful, but there is a need to improve the characterization of far peripheral vision, for both pseudophakic and phakic eyes. Perimetry is the main quantitative test, but the purpose is to evaluate pathologies rather than characterize vision (and object and image regions are no longer uniquely related in the pseudophakic eye). The maximum visual angle is approximately 105 0 , but there is limited information about variations with age, race, or refractive error (in case there is an unexpected link with the development of myopia), or about how clear cornea, iris location, and the limiting retina are related. Also, the detection of peripheral motion is widely recognized to be important, yet rarely evaluated. Overall, people rarely complain specifically about this visual region, but with "normal" vision including an IOL for >5% of people, and increasing interest in virtual reality and augmented reality, there are new reasons to characterize peripheral vision more completely. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Treatment of painful diabetic peripheral neuropathy.

    Science.gov (United States)

    Rosenberg, Casandra J; Watson, James C

    2015-02-01

    Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

  12. Peripheral Red Blood Cell Split Chimerism as a Consequence of Intramedullary Selective Apoptosis of Recipient Red Blood Cells in a Case of Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    Marco Marziali

    2014-08-01

    Full Text Available Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia. After the transplant, the patient showed 36% donor hematopoietic stem cells in the bone marrow, whereas in the peripheral blood there was evidence of 80%  circulating donor red blood cells (RBC. The analysis of apoptosis at the Bone Marrow  level suggests that Fas might contribute to the cell death of host erythroid precursors. The increase in NK cells and the regulatory T cell population observed in this patient suggests that these cells might contribute to the condition of mixed chimerism.

  13. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

    Science.gov (United States)

    Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

    2016-03-15

    Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

  14. Vascular access in neonatology: peripherally inserted central catheter and peripheral venous catheter

    Directory of Open Access Journals (Sweden)

    Marcia Lienemann

    2014-04-01

    The objective of this paper is to present aspects of peripherally inserted central catheter and peripheral venous catheter, highlighting important points in choosing the type of access. For the passage of peripherally inserted central catheter is previously performing specific course necessary, while the primary indication occurs when it is necessary to access the patient's stay for a long period of time. Whereas peripheral venipuncture is the most appropriate in cases of needing an IV line quickly and safely, for the administration of fluids, blood collection, blood transfusion and other.

  15. A tritherapy combination of inactivated allogeneic leukocytes infusion and cell vaccine with cyclophosphamide in a sequential regimen enhances antitumor immunity

    OpenAIRE

    Yishu Tang; Wenbo Ma; Chunxia Zhou; Dongmei Wang; Shuren Zhang

    2018-01-01

    Background: Tumor-induced immunosuppression can impede tumor-specific immune responses and limit the effects of cancer immunotherapy. The aim of this study was to investigate the possible effects of sequential chemoimmunotherapeutic strategies to enhance antitumor immune responses. Methods: Using the E7-expressing tumor TC-1 as the tumor model, the treatment groups were divided into the following groups: (1) inactivated allogeneic leukocyte infusion (ALI), (2) ALI + MMC-inactivated TC-1 cell ...

  16. Multicentre standardisation of a clinical grade procedure for the preparation of allogeneic platelet concentrates from umbilical cord blood

    Science.gov (United States)

    Rebulla, Paolo; Pupella, Simonetta; Santodirocco, Michele; Greppi, Noemi; Villanova, Ida; Buzzi, Marina; De Fazio, Nicola; Grazzini, Giuliano

    2016-01-01

    Background In addition to a largely prevalent use for bleeding prophylaxis, platelet concentrates from adult blood have also been used for many years to prepare platelet gels for the repair of topical skin ulcers. Platelet gel can be obtained by activation of fresh, cryopreserved, autologous or allogeneic platelet concentrates with calcium gluconate, thrombin and/or batroxobin. The high content of tissue regenerative factors in cord blood platelets and the widespread availability of allogeneic cord blood units generously donated for haematopoietic transplant but unsuitable for this use solely because of low haematopoietic stem cell content prompted us to develop a national programme to standardise the production of allogeneic cryopreserved cord blood platelet concentrates (CBPC) suitable for later preparation of clinical-grade cord blood platelet gel. Materials and methods Cord blood units collected at public banks with total nucleated cell counts 150×109/L and volume >50 mL, underwent soft centrifugation within 48 hours of collection. Platelet-rich plasma was centrifuged at high speed to obtain a CBPC with target platelet concentration of 800–1,200×109/L, which was cryopreserved, without cryoprotectant, below −40 °C. Results During 14 months, 13 banks produced 1,080 CBPC with mean (± standard deviation) volume of 11.4±4.4 mL and platelet concentration of 1,003±229×109/L. Total platelet count per CBPC was 11.3±4.9×109. Platelet recovery from cord blood was 47.7±17.8%. About one-third of cord blood units donated for haematopoietic transplant could meet the requirements for preparation of CBPC. The cost of preparation was € 160.92/CBPC. About 2 hours were needed for one technician to prepare four CBPC. Discussion This study yielded valuable scientific and operational information regarding the development of clinical trials using allogeneic CBPC. PMID:26509822

  17. A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient

    DEFF Research Database (Denmark)

    Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik

    2013-01-01

    Post-transplant infections in allogeneic haematopoietic cell transplant (allo-HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need...... for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non-fatal case of Lichtheimia corymbifera infection in an allo-HCT recipient....

  18. Allogeneic cultured keratinocytes vs. cadaveric skin to cover wide-mesh autogenous split-thickness skin grafts.

    Science.gov (United States)

    Monstrey, S; Beele, H; Kettler, M; Van Landuyt, K; Blondeel, P; Matton, G; Naeyaert, J M

    1999-09-01

    Improved shock therapy has extended the limits of survival in patients with massive burns, and nowadays skin coverage has become the major problem in burn management. The use of mesh skin grafts is still the simplest technique to expand the amount of available donor skin. However, very wide-mesh skin grafts take a very long time to heal, often resulting in unaesthetic scar formation. On the other hand, allogeneic cultured keratinocytes have been reported as a natural source of growth factors and thus could be useful to improve wound healing of these wide-mesh grafts. A clinical study was performed to compare the use of cryopreserved allogeneic cultured keratinocytes vs. the traditional cadaveric skin as a double layer over widely expanded autogenous skin grafts. This procedure was performed in 18 pairs of full-thickness burn wounds (with similar depth and location) in 11 severely burned patients. Early clinical evaluation was made at 2, 3, and 4 to 5 weeks. Parameters such as epithelialization, granulation tissue formation, infection, and scar formation were evaluated. Biopsies were taken to compare the histological characteristics of the epidermis, the epidermal-dermal junction, and the dermis. Late evaluations were performed at 6 and 12 months regarding color, softness, thickness, and subjective feeling of the scar tissue. Aside from a faster (p keratinocyte group at 2 weeks, there were no statistically different results in any of the early evaluated parameters, neither clinically nor histologically. At long-term follow-up, clinical results and scar characteristics were not significantly different in the two compared groups. It is concluded from the results of this study that, during the early phase, epithelialization was faster with allogeneic cultured keratinocytes compared with cadaveric skin. However, taking into account the substantial difference in costs, the described use of cryopreserved allogeneic cultured keratinocytes as a double layer on meshed

  19. Impact of oral gut decontamination on Staphylococcus aureus colonisation in patients undergoing allogeneic haematopoietic stem cell transplantation.

    Science.gov (United States)

    Wilk, C Matthias; Weber, Isabel; Seidl, Kati; Rachmühl, Carole; Holzmann-Bürgel, Anne; Müller, Antonia M S; Kuster, Stefan P; Schanz, Urs; Zinkernagel, Annelies S

    2017-12-01

    Recipients of allogeneic haematopoietic stem cell transplantation (allo-HSCT) are severely immunocompromised and are at increased risk of infection. In this prospective, observational, single-centre study including 110 allo-HSCT recipients, the rate of Staphylococcus aureus colonisation was reduced from 11.8% to 0% (P <0.001) following peritransplant oral gut decontamination. No invasive S. aureus infections were observed. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Angioinvasive pulmonary aspergillosis after allogeneic bone marrow transplantation: clinical and high-resolution computed tomography findings in 12 cases

    OpenAIRE

    Gasparetto, Emerson L.; Souza, Carolina A.; Tazoniero, Priscilla; Davaus, Taisa; Escuissato, Dante L.; Marchiori, Edson

    2007-01-01

    The aim of this study was to present the clinical and high-resolution CT scan findings of angioinvasive pulmonary aspergillosis (APA) in 12 patients who underwent allogeneic bone marrow transplantation (BMT). The CT scans were reviewed by three chest radiologists who assessed the pattern and distribution of findings by consent. There were 7 (58%) female and 5 (42%) male patients, with aging between 5 and 50 years (average of 26 years). All patients were submitted to BMT for the treatment of h...

  1. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML).

    Science.gov (United States)

    Goodyear, Oliver C; Dennis, Mike; Jilani, Nadira Y; Loke, Justin; Siddique, Shamyla; Ryan, Gordon; Nunnick, Jane; Khanum, Rahela; Raghavan, Manoj; Cook, Mark; Snowden, John A; Griffiths, Mike; Russell, Nigel; Yin, John; Crawley, Charles; Cook, Gordon; Vyas, Paresh; Moss, Paul; Malladi, Ram; Craddock, Charles F

    2012-04-05

    Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD.

  2. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

    International Nuclear Information System (INIS)

    Nakamura, H.; Gress, R.E.

    1990-01-01

    Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

  3. Allogenic bone graft viability after hip revision arthroplasty assessed by dynamic [18F]fluoride ion positron emission tomography

    International Nuclear Information System (INIS)

    Piert, M.; Becker, H.D.; Winter, E.; Becker, G.A.; Bilger, K.; Machulla, H.J.; Mueller-Schauenburg, W.; Bares, R.

    1999-01-01

    The biological fate of allogenic bone grafts in the acetabular cavity and their metabolic activity after acetabular augmentation is uncertain but is most important for the stability of hip implants after hip revision arthroplasty. The aim of this study was to quantify regional bone metabolism after hip replacement operations. Dynamic [ 18 F]fluoride ion positron emission tomography (PET) was used to investigate the metabolic activity of acetabular allogenic bone grafts and genuine bone, either 3-6 weeks (short-term group, n = 9) or 5 months to 9 years (long-term group, n = 10) after hip revision arthroplasty. Applying a three-compartment model, the fluoride influx constant was calculated from individually fitted rate constants (K nlf ) and by Patlak graphical analysis (K pat ). The results were compared with genuine cancellous and cortical acetabular bone of contralateral hips without surgical trauma (n = 7). In genuine cortical bone, K nlf was significantly increased in short- (+140.9%) and long-term (+100.0%) groups compared with contralateral hips. Allogenic bone grafts were characterised by a significantly increased K nlf in the short-term group (+190.9%) compared with contralateral hips, but decreased almost to the baseline levels of contralateral hips (+45.5%) in the long-term. Values of K nlf cor-related with the rate constant K 1 in genuine (r = 0.89, P pat values were highly correlated with K nlf measurements in all regions. (orig.)

  4. Allogeneic stem cell transplantation for acute myeloid leukemia with del(7q) following untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    DeFilipp, Zachariah; Huynh, Donny V; Fazal, Salman; Sahovic, Entezam

    2012-01-01

    The development of hematologic malignancy in the presence of chronic lymphocytic leukemia (CLL) is rare. We present a case of acute myeloid leukemia (AML) with del(7q) occurring in a patient with a 4-year history of untreated CLL. Application of flow cytometry and immunohistochemistry allowed for characterization of two distinct coexisting malignant cell populations. After undergoing induction and consolidation chemotherapy, the patient achieved complete remission of AML with the persistence of CLL. Allogeneic transplantation was pursued given his unfavorable cytogenetics. Subsequent matched unrelated donor allogeneic stem cell transplantation resulted in full engraftment and complete remission, with no evidence of AML or CLL. Due to a scarcity of reported cases, insight into treatment and prognosis in cases of concurrent AML and CLL is limited. However, prognosis seems dependent on the chemosensitivity of AML. CLL did not have a detrimental effect on treatment or transplant outcome in our case. This is the first reported case of concomitant de novo AML and CLL to undergo allogeneic transplantation. The patient remained in complete hematologic and cytogenetic remission of both malignancies over a year after transplantation.

  5. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    Science.gov (United States)

    Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L

    2013-01-01

    To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

  6. Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients.

    Science.gov (United States)

    Yasu, Takeo; Konuma, Takaaki; Kato, Seiko; Kurokawa, Yosuke; Takahashi, Satoshi; Tojo, Arinobu

    2016-10-01

    Voriconazole (VRC) is widely used as prophylaxis and in the treatment of invasive fungal disease (IFD) after allogeneic hematopoietic cell transplantation (HCT). We retrospectively examined the results of VRC therapeutic drug monitoring (TDM) in allogeneic HCT recipients. A total of 474 samples were obtained from 59 adult patients who received VRC during the first 100 days following HCT between 2009 and 2014 in our institute. Seventeen patients received VRC for prophylaxis of IFD, and 42 received VRC for the empirical or preemptive therapy for IFD. A total of 299 samples (63 %) were obtained during the administration of the intravenous form of VRC. The median VRC daily dose based on the actual body weight was 6.68 mg/kg/day (range, 1.92-10.41 mg/kg/day). The median VRC trough level was 0.99 mg/l (range, lansoprazole as compared to rabeprazole (P lansoprazole and rabeprazole have different effects on the plasma VRC trough levels in the allogeneic HCT recipients.

  7. Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells

    International Nuclear Information System (INIS)

    Britt, L.D.; Scharp, D.W.; Lacy, P.E.; Slavin, S.

    1982-01-01

    Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression

  8. Effects of combined radiation-burn injury on survival rate of allogeneic skin grafts and immune reaction in rats

    International Nuclear Information System (INIS)

    Ran Xinze; Yan Yongtang; Cheng Tianmin; Li Yuan; Wei Shuqing

    1996-01-01

    The effects of combined radiation-burn injury on survival rate of allogeneic skin grafts and immune reaction were studied in rats with combined injury of 3-8 Gy 60 Co γ-ray irradiation plus 15% total body surface area full thickness burn induced by exposure to a 5 kw bromotungsten lamp. The allogeneic skin was transplanted 24 hours after injury. It was found that all the skin grafts failed to survive in 10 days and the immune reaction significantly increased in the early stage of burn injury. But the immune reaction was obviously suppressed by the combined radiation-burn injury. The survival rates of skin grafts were 20% and 30% in the combined injury of burn plus 3 and 4 Gy irradiation respectively. When the radiation doses increased to 5,6 and 8 Gy, the survival rates elevated to 69%, 88% and 100% respectively (in the group of 8 Gy, bone marrow transplantation was conducted before receiving skin graft). At day 30 post-transplantation the survival rates were still 36%, 42% and 100% respectively. Compared with burn group, there was a significant difference in survival rate when the radiation doses were higher than 5 Gy. These results indicate that the survival rate of the allogeneic skin graft increases concurrently with the increase in radiation dose and decreases with the elapse of the post-transplantation time

  9. Indicators of allogenic interactions of lymphocytes in spouses as additional diagnostic and prognostic criteria of immune forms of reproductive failures

    Directory of Open Access Journals (Sweden)

    Belenkova O.V.

    2013-12-01

    Full Text Available Research objective: to search new laboratory approaches to the diagnostics of immune forms of reproductive failures. Materials and methods. Retrospective research a case — control of 54 married couples with idiopathic reproductive failures (in the anamnesis — 3 and more spontaneously interrupted pregnancy in the 4-8th weeks and 47 married couples having two and more children has been conducted. Results. It has been revealed that at the immune form of reproductive failures increase of cells of level A- mononuclear cells, expression of HLDR takes place that promotes tolerance cancellation to allogenic germs and to immune interruption of pregnancy. At reproductive failures female au-toserum positively influences activation of T-lymphocyte (CD3 +/HLADR + that may lead to the death of half- allogenic germ. Conclusion. Level of expression of CD3 and HLADR on CD45 + of mixed allogenic mononuclear cells of spouses may serve as a diagnostic significant criterion for revealing immune reasons of reproductive failures.

  10. Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors

    Directory of Open Access Journals (Sweden)

    Chuan Jin

    2014-01-01

    Full Text Available Adoptive T-cell therapy of cancer is a treatment strategy where T cells are isolated, activated, in some cases engineered, and expanded ex vivo before being reinfused to the patient. The most commonly used T-cell expansion methods are either anti-CD3/CD28 antibody beads or the “rapid expansion protocol” (REP, which utilizes OKT-3, interleukin (IL-2, and irradiated allogeneic feeder cells. However, REP-expanded or bead-expanded T cells are sensitive to the harsh tumor microenvironment and often short-lived after reinfusion. Here, we demonstrate that when irradiated and preactivated allosensitized allogeneic lymphocytes (ASALs are used as helper cells to license OKT3-armed allogeneic mature dendritic cells (DCs, together they expand target T cells of high quality. The ASAL/DC combination yields an enriched Th1-polarizing cytokine environment (interferon (IFN-γ, IL-12, IL-2 and optimal costimulatory signals for T-cell stimulation. When genetically engineered antitumor T cells were expanded by this coculture system, they showed better survival and cytotoxic efficacy under oxidative stress and immunosuppressive environment, as well as superior proliferative response during tumor cell killing compared to the REP protocol. Our result suggests a robust ex vivo method to expand T cells with improved quality for adoptive cancer immunotherapy.

  11. Perioperative Allogeneic Red Blood-Cell Transfusion Associated with Surgical Site Infection After Total Hip and Knee Arthroplasty.

    Science.gov (United States)

    Everhart, Joshua S; Sojka, John H; Mayerson, Joel L; Glassman, Andrew H; Scharschmidt, Thomas J

    2018-02-21

    Perioperative allogeneic red blood-cell transfusion is a suspected risk factor for surgical site infection (SSI) after total joint arthroplasty (TJA), but the interrelationships among SSI risk, transfusion dose, preoperative anemia, and the presence of coagulopathies have not been well described. Data on SSI within 1 year after surgery as well as on transfusion with blood products within 30 days after surgery were obtained for 6,788 patients who had undergone primary or revision total hip or knee arthroplasty from 2000 to 2011 in a single hospital system. Multivariate logistic regression modeling was used to determine the independent association between allogeneic red blood-cell transfusion and SSI. There was a dose-dependent association between allogeneic red blood-cell transfusion and SSI, with the infection rate increasing as the transfusion dose increased from 1 unit (odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.38, 2.79; p 3 units (OR = 7.40; CI = 4.91, 11.03; p conservation strategies. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  12. Semi-allogeneic dendritic cells can induce antigen-specific T-cell activation, which is not enhanced by concurrent alloreactivity.

    Science.gov (United States)

    Wells, James W; Cowled, Chris J; Darling, David; Guinn, Barbara-Ann; Farzaneh, Farzin; Noble, Alistair; Galea-Lauri, Joanna

    2007-12-01

    Alloreactive T-cell responses are known to result in the production of large amounts of proinflammatory cytokines capable of activating and maturing dendritic cells (DC). However, it is unclear whether these allogeneic responses could also act as an adjuvant for concurrent antigen-specific responses. To examine effects of simultaneous alloreactive and antigen-specific T-cell responses induced by semi-allogeneic DC. Semi-allogeneic DC were generated from the F(1) progeny of inbred strains of mice (C57BL/6 and C3H, or C57BL/6 and DBA). We directly primed antigen-specific CD8(+) and CD4(+) T-cells from OT-I and OT-II mice, respectively, in the absence of allogeneic responses, in vitro, and in the presence or absence of alloreactivity in vivo. In vitro, semi-allogeneic DC cross-presented ovalbumin (OVA) to naïve CD8(+) OT-I transgenic T-cells, primed naïve CD4(+) OT-II transgenic T-cells and could stimulate strong alloreactive T-cell proliferation in a primary mixed lymphocyte reaction (MLR). In vivo, semi-allogeneic DC migrated efficiently to regional lymph nodes but did not survive there as long as autologous DC. In addition, they were not able to induce cytotoxic T-lymphocyte (CTL) activity to a target peptide, and only weakly stimulated adoptively transferred OT-II cells. The CD4(+) response was unchanged in allo-tolerized mice, indicating that alloreactive T-cell responses could not provide help for concurrently activated antigen-specific responses. In an EL4 tumour-treatment model, vaccination with semi-allogeneic DC/EL4 fusion hybrids, but not allogeneic DC/EL4 hybrids, significantly increased mouse survival. Expression of self-Major histocompatibility complex (MHC) by semi-allogeneic DC can cause the induction of antigen-specific immunity, however, concurrently activated allogeneic bystander responses do not provide helper or adjuvant effects.

  13. Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group.

    Science.gov (United States)

    Itonaga, H; Sawayama, Y; Taguchi, J; Honda, S; Taniguchi, H; Makiyama, J; Matsuo, E; Sato, S; Ando, K; Imanishi, D; Imaizumi, Y; Yoshida, S; Hata, T; Moriuchi, Y; Fukushima, T; Miyazaki, Y

    2015-04-01

    Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (PSCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.

  14. Case report of a patient with peripheral facial nerve palsy

    OpenAIRE

    Rysová, Jana

    2013-01-01

    Title of bachelor's thesis: Case report of a patient with peripheral facial nerve palsy Summary: Teoretical part of bachelor's thesis contains theoretical foundation of peripheral facial nerve palsy. Practical part of bachelor's thesis contains physiotherapeutic case report of patient with peripheral facial nerve palsy. Key words: peripheral facial nerve palsy, casuistry, rehabilitation

  15. Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

    Science.gov (United States)

    Hayashi-Takagi, Akiko; Vawter, Marquis P; Iwamoto, Kazuya

    2014-06-15

    Peripheral samples, such as blood and skin, have been used for decades in psychiatric research as surrogates for central nervous system samples. Although the validity of the data obtained from peripheral samples has been questioned and other state-of-the-art techniques, such as human brain imaging, genomics, and induced pluripotent stem cells, seem to reduce the value of peripheral cells, accumulating evidence has suggested that revisiting peripheral samples is worthwhile. Here, we re-evaluate the utility of peripheral samples and argue that establishing an understanding of the common signaling and biological processes in the brain and peripheral samples is required for the validity of such models. First, we present an overview of the available types of peripheral cells and describe their advantages and disadvantages. We then briefly summarize the main achievements of omics studies, including epigenome, transcriptome, proteome, and metabolome analyses, as well as the main findings of functional cellular assays, the results of which imply that alterations in neurotransmission, metabolism, the cell cycle, and the immune system may be partially responsible for the pathophysiology of major psychiatric disorders such as schizophrenia. Finally, we discuss the future utility of peripheral samples for the development of biomarkers and tailor-made therapies, such as multimodal assays that are used as a battery of disease and trait pathways and that might be potent and complimentary tools for use in psychiatric research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  16. Peripheral dose outside applicators in electron beams

    International Nuclear Information System (INIS)

    Chow, James C L; Grigorov, Grigor N

    2006-01-01

    The peripheral dose outside the applicators in electron beams was studied using a Varian 21 EX linear accelerator. To measure the peripheral dose profiles and point doses for the applicator, a solid water phantom was used with calibrated Kodak TL films. Peak dose spot was observed in the 4 MeV beam outside the applicator. The peripheral dose peak was very small in the 6 MeV beam and was ignorable at higher energies. Using the 10 x 10 cm 2 cutout and applicator, the dose peak for the 4 MeV beam was about 12 cm away from the field central beam axis (CAX) and the peripheral dose profiles did not change with depths measured at 0.2, 0.5 and 1 cm. The peripheral doses and profiles were further measured by varying the angle of obliquity, cutout and applicator size for the 4 MeV beam. The local peak dose was increased with about 3% per degree angle of obliquity, and was about 1% of the prescribed dose (angle of obliquity equals zero) at 1 cm depth in the phantom using the 10 x 10 cm 2 cutout and applicator. The peak dose position was also shifted 7 mm towards the CAX when the angle of obliquity was increased from 0 to 15 deg. (note)

  17. Should elderly patients with higher-risk myelodysplastic syndromes undergo allogeneic hematopoietic stem cell transplantation?

    Science.gov (United States)

    Zeidan, Amer M; Gore, Steven D

    2013-10-01

    Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies characterized by dysplastic changes, ineffective hematopoiesis and variable risk of leukemic progression. At diagnosis, 86% of MDS patients are ≥60 years. Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients, adds a median of only 9.5 months to life. Allogeneic stem cell transplantation (alloSCT) remains the only potentially curative approach. Despite recent improvements including use of reduced intensity conditioning (RIC) that decrease transplant-related mortality, alloSCT continues to be used rarely in elderly MDS. There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS patients, especially in direct comparison with azanucleosides. In this paper, the authors di