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.

Periodontal disease detection in primary and mixed dentitions.

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Nobre, C M Guimarães; Fernandes-Costa, A N; de Melo Soares, M S; Pugliesi, D M Carvalho; de Vasconcelos Gurgel, B C

2016-10-01

This was to compare the periodontal status of children with primary and mixed dentition at the time of their first consultation. Children (200), aged 0-12 years (156 with mixed and 44 with primary dentition), were examined by assessing their simplified plaque index (PI) and simplified periodontal record (PSR). Statistical analysis (Chi-square test) was performed with appropriate software to find any significant associations between sex, type of dentition and PI with the PSR codes (0, 1, 2, 3 and 4). There was no statistically significant difference with regard to gender (p = 0.82). Generalised PI was associated more significantly with mixed dentition (p = 0.025 and higher PSR scores (p periodontal examination in children to diagnose and prevent future periodontal disease and maintain their dentition as well as to identify any associated systemic conditions.

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

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.

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

Primary Issues of Mixed Convection Heat Transfer Phenomena

Energy Technology Data Exchange (ETDEWEB)

Chae, Myeong-Seon; Chung, Bum-Jin [Kyung Hee University, Yongin (Korea, Republic of)

2015-10-15

The computer code analyzing the system operating and transient behavior must distinguish flow conditions involved with convective heat transfer flow regimes. And the proper correlations must be supplied to those flow regimes. However the existing safety analysis codes are focused on the Light Water Reactor and they are skeptical to be applied to the GCRs (Gas Cooled Reactors). One of the technical issues raise by the development of the VHTR is the mixed convection, which occur when the driving forces of both forced and natural convection are of comparable magnitudes. It can be encountered as in channel of the stacked with fuel elements and a decay heat removal system and in VHTR. The mixed convection is not intermediate phenomena with natural convection and forced convection but independent complicated phenomena. Therefore, many researchers have been studied and some primary issues were propounded for phenomena mixed convection. This paper is to discuss some problems identified through reviewing the papers for mixed convection phenomena. And primary issues of mixed convection heat transfer were proposed respect to thermal hydraulic problems for VHTR. The VHTR thermal hydraulic study requires an indepth study of the mixed convection phenomena. In this study we reviewed the classical flow regime map of Metais and Eckert and derived further issues to be considered. The following issues were raised: (1) Buoyancy aided an opposed flows were not differentiated and plotted in a map. (2) Experimental results for UWT and UHF condition were also plotted in the same map without differentiation. (3) The buoyancy coefficient was not generalized for correlating with buoyancy coefficient. (4) The phenomenon analysis for laminarization and returbulization as buoyancy effects in turbulent mixed convection was not established. (5) The defining to transition in mixed convection regime was difficult.

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.

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.

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

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

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

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

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.

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.

Prices versus policy: An analysis of the drivers of the primary fossil fuel mix

International Nuclear Information System (INIS)

Atalla, Tarek; Blazquez, Jorge; Hunt, Lester C.; Manzano, Baltasar

2017-01-01

Energy policymakers often attempt to shape their countries' energy mix, rather than leave it purely to market forces. By calibrating and simulating a Dynamic Stochastic General Equilibrium (DSGE) model, this paper analyzes the primary fossil fuel mix in the USA and compares it to Germany and the UK, given the different evolution of the mixes and the different roles played by relative prices and policy in North America and Europe. It is found that the model explains well the evolution of the primary fossil fuel mix in the USA for the period 1980–2014, suggesting that relative fossil fuel prices generally dominated in determining the mix during this time. However, this is not the case for Germany and the UK. For both countries, the model performs well only for the period after the market-oriented reforms in the 1990s. Additionally, the volatility of private consumption and output for the pre- and post-reform periods is evaluated for Germany and the UK and it is found that the liberalized energy markets brought about a transition from coal to natural gas, but with increased macroeconomic volatility. - Highlights: • Macroeconomic analysis of the importance of prices vs policy in driving the primary fossil fuel mix. • USA primary fossil fuel mix chiefly driven by relative prices since the early 1980s. • Germany and UK primary fossil fuel mix chiefly driven by policy until 1990s. • Germany and UK primary fossil fuel mix chiefly driven by relative prices since early to mid-1990s. • Transition from coal to natural gas in Germany and UK increased macroeconomic volatility.

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).

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.

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.

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...

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

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.

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.

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.

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

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

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

The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

DEFF Research Database (Denmark)

Ødum, Niels; Hofmann, B; Jacobsen, N

1987-01-01

Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

A comparison of post-op haemoglobin levels and allogeneic blood transfusion rates following total knee arthroplasty without drainage or with reinfusion drains.

Science.gov (United States)

Hazarika, Shariff; Bhattacharya, Rajarshi; Bhavikatti, Mainudden; Dawson, Matthew

2010-02-01

The effects of re-infusion drains on the rate of allogeneic blood transfusion and post-op haemoglobin levels in Total Knee Arthroplasty were examined. A group of 22 patients undergoing primary Total Knee Arthroplasty using a CBCII Constavac Stryker re-infusion drainage system were compared with a group of 30 patients, matched for age, sex and type of prosthesis but without any drain usage. The re-infusion drain.group had a significantly lower day 1 and day 3 post-operative haemoglobin compared to the non-drainage group. The re-infusion drain group had a higher allogenic transfusion rate compared to the non-drainage group. There were no significant differences between the two groups regarding the rate of wound and transfusion related complications and mean length of post-operative stay. We found that reinfusion drains were ineffective in reducing allogeneic transfusion requirements as compared with non-drainage in total knee arthroplasty.

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.

Effects of T cell depletion in radiation bone marrow chimeras. I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD

International Nuclear Information System (INIS)

Sykes, M.; Sheard, M.; Sachs, D.H.

1988-01-01

The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation

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...

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.

[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.

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.

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.

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

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.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery

Science.gov (United States)

Warner, Matthew A; Welsby, Ian J; Norris, Phillip J; Silliman, Christopher C; Armour, Sarah; Wittwer, Erica D; Santrach, Paula J; Meade, Laurie A; Liedl, Lavonne M; Nieuwenkamp, Chelsea M; Douthit, Brian; van Buskirk, Camille M; Schulte, Phillip J; Kor, Daryl J

2017-01-01

Introduction The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. Methods and analysis This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon’s two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Ethics and dissemination Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC

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

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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.

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.

'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

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

Validation of ACG Case-mix for equitable resource allocation in Swedish primary health care.

Science.gov (United States)

Zielinski, Andrzej; Kronogård, Maria; Lenhoff, Håkan; Halling, Anders

2009-09-18

Adequate resource allocation is an important factor to ensure equity in health care. Previous reimbursement models have been based on age, gender and socioeconomic factors. An explanatory model based on individual need of primary health care (PHC) has not yet been used in Sweden to allocate resources. The aim of this study was to examine to what extent the ACG case-mix system could explain concurrent costs in Swedish PHC. Diagnoses were obtained from electronic PHC records of inhabitants in Blekinge County (approx. 150,000) listed with public PHC (approx. 120,000) for three consecutive years, 2004-2006. The inhabitants were then classified into six different resource utilization bands (RUB) using the ACG case-mix system. The mean costs for primary health care were calculated for each RUB and year. Using linear regression models and log-cost as dependent variable the adjusted R2 was calculated in the unadjusted model (gender) and in consecutive models where age, listing with specific PHC and RUB were added. In an additional model the ACG groups were added. Gender, age and listing with specific PHC explained 14.48-14.88% of the variance in individual costs for PHC. By also adding information on level of co-morbidity, as measured by the ACG case-mix system, to specific PHC the adjusted R2 increased to 60.89-63.41%. The ACG case-mix system explains patient costs in primary care to a high degree. Age and gender are important explanatory factors, but most of the variance in concurrent patient costs was explained by the ACG case-mix system.

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.

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.

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.

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.

Validation of ACG Case-mix for equitable resource allocation in Swedish primary health care

Directory of Open Access Journals (Sweden)

Kronogård Maria

2009-09-01

Full Text Available Abstract Background Adequate resource allocation is an important factor to ensure equity in health care. Previous reimbursement models have been based on age, gender and socioeconomic factors. An explanatory model based on individual need of primary health care (PHC has not yet been used in Sweden to allocate resources. The aim of this study was to examine to what extent the ACG case-mix system could explain concurrent costs in Swedish PHC. Methods Diagnoses were obtained from electronic PHC records of inhabitants in Blekinge County (approx. 150,000 listed with public PHC (approx. 120,000 for three consecutive years, 2004-2006. The inhabitants were then classified into six different resource utilization bands (RUB using the ACG case-mix system. The mean costs for primary health care were calculated for each RUB and year. Using linear regression models and log-cost as dependent variable the adjusted R2 was calculated in the unadjusted model (gender and in consecutive models where age, listing with specific PHC and RUB were added. In an additional model the ACG groups were added. Results Gender, age and listing with specific PHC explained 14.48-14.88% of the variance in individual costs for PHC. By also adding information on level of co-morbidity, as measured by the ACG case-mix system, to specific PHC the adjusted R2 increased to 60.89-63.41%. Conclusion The ACG case-mix system explains patient costs in primary care to a high degree. Age and gender are important explanatory factors, but most of the variance in concurrent patient costs was explained by the ACG case-mix system.

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.

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation

International Nuclear Information System (INIS)

Fuller, L.; Flaa, C.; Jaffe, D.; Strauss, J.; Kyriakides, G.K.; Miller, J.

1983-01-01

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The ''naturally occurring'' T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents

Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

International Nuclear Information System (INIS)

Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

1982-01-01

When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

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...

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

Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

Science.gov (United States)

de Masson, Adèle; Beylot-Barry, Marie; Bouaziz, Jean-David; de Latour, Régis Peffault; Aubin, François; Garciaz, Sylvain; d’Incan, Michel; Dereure, Olivier; Dalle, Stéphane; Dompmartin, Anne; Suarez, Felipe; Battistella, Maxime; Vignon-Pennamen, Marie-Dominique; Rivet, Jacqueline; Adamski, Henri; Brice, Pauline; François, Sylvie; Lissandre, Séverine; Turlure, Pascal; Wierzbicka-Hainaut, Ewa; Brissot, Eolia; Dulery, Rémy; Servais, Sophie; Ravinet, Aurélie; Tabrizi, Reza; Ingen-Housz-Oro, Saskia; Joly, Pascal; Socié, Gérard; Bagot, Martine

2014-01-01

The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38–0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41–0.77) and progression-free survival 31% (95%CI: 0.19–0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1–0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3–6.2; P=0.01) but also transplant-related mortality (HR=10−7, 95%CI: 4.10−8–2.10−7; P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides. PMID:24213148

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

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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.

Point-of-care washing of allogeneic red blood cells for the prevention of transfusion-related respiratory complications (WAR-PRC): a protocol for a multicenter randomised clinical trial in patients undergoing cardiac surgery.

Science.gov (United States)

Warner, Matthew A; Welsby, Ian J; Norris, Phillip J; Silliman, Christopher C; Armour, Sarah; Wittwer, Erica D; Santrach, Paula J; Meade, Laurie A; Liedl, Lavonne M; Nieuwenkamp, Chelsea M; Douthit, Brian; van Buskirk, Camille M; Schulte, Phillip J; Carter, Rickey E; Kor, Daryl J

2017-08-18

The transfusion-related respiratory complications, transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO), are leading causes of transfusion-related morbidity and mortality. At present, there are no effective preventive strategies with red blood cell (RBC) transfusion. Although mechanisms remain incompletely defined, soluble biological response modifiers (BRMs) within the RBC storage solution may play an important role. Point-of-care (POC) washing of allogeneic RBCs may remove these BRMs, thereby mitigating their impact on post-transfusion respiratory complications. This is a multicenter randomised clinical trial of standard allogeneic versus washed allogeneic RBC transfusion for adult patients undergoing cardiac surgery testing the hypothesis that POC RBC washing is feasible, safe, and efficacious and will reduce recipient immune and physiologic responses associated with transfusion-related respiratory complications. Relevant clinical outcomes will also be assessed. This investigation will enrol 170 patients at two hospitals in the USA. Simon's two-stage design will be used to assess the feasibility of POC RBC washing. The primary safety outcomes will be assessed using Wilcoxon Rank-Sum tests for continuous variables and Pearson chi-square test for categorical variables. Standard mixed modelling practices will be employed to test for changes in biomarkers of lung injury following transfusion. Linear regression will assess relationships between randomised group and post-transfusion physiologic measures. Safety oversight will be conducted under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained by the DSMB as well as the institutional review boards at each institution prior to enrolling the first study participant. This study aims to provide important information regarding the feasibility of POC washing of allogeneic RBCs and its potential impact on ameliorating

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

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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.

The effect of mixing on fermentation of primary solids, glycerol, and biodiesel waste.

Science.gov (United States)

Ghasemi, Marzieh; Randall, Andrew A

2018-03-01

In this study, the effect of mixing on volatile fatty acid (VFA) production and composition was investigated through running five identical bench-scale reactors that were filled with primary solid and dosed with either pure glycerol or biodiesel waste. Experimental results revealed that there was an inverse correlation between the mixing intensity and the VFA production. The total VFA production in the un-mixed reactor was 9,787 ± 3,601 mg COD/L, whereas in the reactor mixed at 100 rpm this dropped to 3,927 ± 1,175 mg COD/L, while both types of reactor were dosed with pure glycerol at the beginning of each cycle to reach the initial concentration of 1,000 mg/L (1,217 mg COD/L). Propionic acid was the dominant VFA in all the reactors except the reactor mixed at 30 rpm. It is hypothesized that low mixing facilitated hydrogen transfer between obligate hydrogen producing acetogens (OHPA) and hydrogen consuming acidogens in these non-methanogenic reactors. Also, in a narrower range of mixing (0 or 7 rpm), the total VFA production in biodiesel waste-fed reactors was considerably higher than that of pure glycerol-fed reactors.

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

Science.gov (United States)

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.

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.)

Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection

DEFF Research Database (Denmark)

Hokland, M; Jacobsen, N; Ellegaard, J

1988-01-01

Natural killer (NK) cell function was followed sequentially after allogeneic bone marrow transplantation (BMT) using three approaches: (1) chromium-release assay with purified mononuclear effector cells, (2) chromium-release assay with whole blood effectors, and 3) enumeration of lymphocytes......) infections (primary or reactivated). In contrast, the presence of graft-versus-host (GVH) disease did not associate with consistent changes in the NK parameters measured here. After the first month of increase, NK declined reaching levels near those observed in their respective bone marrow donors at day 90...

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.

Successful Treatment of Richter Transformation with Ibrutinib in a Patient with Chronic Lymphocytic Leukemia following Allogeneic Hematopoietic Stem Cell Transplant

Directory of Open Access Journals (Sweden)

Samip Master

2017-06-01

Full Text Available Patients with chronic lymphocytic leukemia (CLL who progress to Richter transformation (RT have a poor prognosis. Multi-agent chemotherapy regimens do not have good response rates. There are few case reports on the use of ibrutinib in RT. Here, we present a patient who was heavily pretreated for CLL, including allogeneic stem cell transplant, and progressed to RT. She had a mixed response to multi-agent chemotherapy and was started on ibrutinib. She had a complete response for 16 months on single-agent ibrutinib with minimal toxicity.

Allogenic and Autogenic Signals in the Detrital Zircon U-Pb Record of the Deep-Sea Bengal Fan

Science.gov (United States)

Blum, M. D.; Rogers, K. G.; Gleason, J. D.; Najman, Y.

2017-12-01

The Himalayan-sourced Ganges-Brahmaputra river system and the deep-sea Bengal Fan represent Earth's largest sediment-dispersal system. This presentation summarizes a new detrital zircon U-Pb (DZ) provenance record from the Bengal Fan from cores collected during IODP Expedition 354, with coring sites located 1350 km downdip from the shelf margin. Each of our 15 samples were collected from medium- to fine-grained turbidite sand and, based on shipboard biostratigraphic analyses, our samples are late Miocene to late Pleistocene in age. Each sample was analyzed by LA-ICPMS at the Arizona Laserchron facility, with an average of n=270 concordant U-Pb ages per sample. Our goals are to use these data to evaluate the influence of allogenic controls vs. autogenic processes on signal propagation from source-to-sink. At the first order, large-scale sediment transfer to the Bengal Fan clearly records the strong tectonic and climatic forcing associated with the Himalayas and Ganges-Brahmaputra system: after up to 2500 km of river transport, and 1350 km of transport in turbidity currents, the DZ record faithfully represents Himalayan source terrains. The sand-rich turbidite part of the record is nevertheless biased towards glacial periods when rivers extended across the shelf in response to climate-forced sea-level fall, and discharged directly to slope canyons. However, only part of the Bengal Fan DZ record represents either the Ganges or the Brahmaputra, with most samples representing varying degrees of mixing of sediments from the two systems: this mixing, or the lack thereof, represents the signal of autogenic avulsions on the delta plain that result in the two river systems delivering sediment separately to the shelf margin, or together as they do today. Within the allogenic framework established by tectonic processes, the climatic system, and global climate-forced sea-level change, the DZ U-Pb record of sediment mixing or the lack thereof provides a fingerprint of autogenic

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

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.

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

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

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.

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...

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

Mixed chimerism to induce tolerance for solid organ transplantation

International Nuclear Information System (INIS)

Wren, S.M.; Nalesnik, M.; Hronakes, M.L.; Oh, E.; Ildstad, S.T.

1991-01-01

Chimerism, or the coexistence of tissue elements from more than one genetically different strain or species in an organism, is the only experimental state that results in the induction of donor-specific transplantation tolerance. Transplantation of a mixture of T-cell-depleted syngeneic (host-type) plus T-cell-depleted allogeneic (donor) bone marrow into a normal adult recipient mouse (A + B----A) results in mixed allogeneic chimerism. Recipient mice exhibit donor-specific transplantation tolerance, yet have full immunocompetence to recognize and respond to third-party transplantation antigens. After complete hematolymphopoietic repopulation at 28 days, animals accept a donor-specific skin graft but reject major histocompatibility complex (MHC) locus-disparate third-party grafts. We now report that permanent graft acceptance can also be achieved when the graft is placed at the time of bone marrow transplantation. Histologically, grafts were viable and had only minimal inflammatory changes. This model may have potential future clinical application for the induction of donor-specific transplantation tolerance

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.

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)

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

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

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

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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

Delayed allogeneic skin graft rejection in CD26-deficient mice.

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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.

Should measures of patient experience in primary care be adjusted for case mix? Evidence from the English General Practice Patient Survey.

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Paddison, Charlotte; Elliott, Marc; Parker, Richard; Staetsky, Laura; Lyratzopoulos, Georgios; Campbell, John L; Roland, Martin

2012-08-01

Uncertainties exist about when and how best to adjust performance measures for case mix. Our aims are to quantify the impact of case-mix adjustment on practice-level scores in a national survey of patient experience, to identify why and when it may be useful to adjust for case mix, and to discuss unresolved policy issues regarding the use of case-mix adjustment in performance measurement in health care. Secondary analysis of the 2009 English General Practice Patient Survey. Responses from 2 163 456 patients registered with 8267 primary care practices. Linear mixed effects models were used with practice included as a random effect and five case-mix variables (gender, age, race/ethnicity, deprivation, and self-reported health) as fixed effects. Primary outcome was the impact of case-mix adjustment on practice-level means (adjusted minus unadjusted) and changes in practice percentile ranks for questions measuring patient experience in three domains of primary care: access; interpersonal care; anticipatory care planning, and overall satisfaction with primary care services. Depending on the survey measure selected, case-mix adjustment changed the rank of between 0.4% and 29.8% of practices by more than 10 percentile points. Adjusting for case-mix resulted in large increases in score for a small number of practices and small decreases in score for a larger number of practices. Practices with younger patients, more ethnic minority patients and patients living in more socio-economically deprived areas were more likely to gain from case-mix adjustment. Age and race/ethnicity were the most influential adjustors. While its effect is modest for most practices, case-mix adjustment corrects significant underestimation of scores for a small proportion of practices serving vulnerable patients and may reduce the risk that providers would 'cream-skim' by not enrolling patients from vulnerable socio-demographic groups.

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

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.

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.

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.

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

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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.

Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditionaing for Allogeneic Canine Marrow Transplantion

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Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

2003-06-15

Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A”-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up.

Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditioning for Allogeneic Canine Marrow Transplantion

International Nuclear Information System (INIS)

Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

2003-01-01

Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up

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.

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

Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

Science.gov (United States)

Davies, L; Brown, T J; Haynes, S; Payne, K; Elliott, R A; McCollum, C

2006-11-01

). Twelve published studies reported full economic evaluations. All but two of the transfusion strategies significantly reduced exposure to allogeneic blood. The relative risk of exposure to allogeneic blood was 0.59 for the pooled trials of cell salvage (95% confidence interval: 0.48 to 0.73). This varied by the type and timing of cell salvage and type of surgical procedure. For cell salvage, the relative risk of allogeneic blood transfusion was higher in cardiac surgery than in orthopaedic surgery. Cell salvage had lower costs and slightly higher quality-adjusted life years compared with all of the alternative transfusion strategies except ANH. The likelihood that cell salvage is cost-effective compared with strategies other than ANH is over 50%. Most of the secondary analyses indicated similar results to the primary analysis. However, the primary and secondary analyses indicated that ANH may be more cost-effective than cell salvage. The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfusion. However, ANH may be more cost-effective than cell salvage. The results of this analysis are subject to the low quality and reliability of the data used and the use of indirect comparisons. This may affect the reliability and robustness of the clinical and economic results. There is a need for further research that includes adequately powered high-quality RCTs to compare directly various blood transfusion strategies. These should include measures of health status, health-related quality of life and patient preferences for alternative transfusion strategies. Observational and tracking studies are needed to estimate reliably the incidence of adverse events and infections transmitted during blood transfusion and to identify the lifetime consequences of the serious hazards of transfusion on mortality, health status and health-related quality of life.

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

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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.

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

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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.

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

Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

Science.gov (United States)

Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

2012-08-15

Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

Proactive cancer care in primary care: a mixed-methods study.

Science.gov (United States)

Kendall, Marilyn; Mason, Bruce; Momen, Natalie; Barclay, Stephen; Munday, Dan; Lovick, Roberta; Macpherson, Stella; Paterson, Euan; Baughan, Paul; Cormie, Paul; Kiehlmann, Peter; Free, Amanda; Murray, Scott A

2013-06-01

Current models of post-treatment cancer care are based on traditional practices and clinician preference rather than evidence of benefit. To assess the feasibility of using a structured template to provide holistic follow-up of patients in primary care from cancer diagnosis onwards. A two-phase mixed methods action research project. An electronic cancer ongoing review document (CORD) was first developed with patients and general practitioners, and used with patients with a new diagnosis of cancer. This was evaluated through documentary analysis of the CORDs, qualitative interviews with patients, family carers and health professionals and record reviews. The records of 107 patients from 13 primary care teams were examined and 45 interviews conducted. The document was started in 54% of people with newly diagnosed cancer, and prompted clear documentation of multidimension needs and understanding. General practitioners found using the document helped to structure consultations and cover psychosocial areas, but they reported it needed to be better integrated in their medical records with computerized prompts in place. Few clinicians discussed the review openly with patients, and the template was often completed afterwards. Anticipatory cancer care from diagnosis to cure or death, 'in primary care', is feasible in the U.K. and acceptable to patients, although there are barriers. The process promoted continuity of care and holism. A reliable system for proactive cancer care in general practice supported by hospital specialists may allow more survivorship care to be delivered in primary care, as in other long-term conditions.

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.

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....

Primary Student-Teachers' Conceptual Understanding of the Greenhouse Effect: A mixed method study

Science.gov (United States)

Ratinen, Ilkka Johannes

2013-04-01

The greenhouse effect is a reasonably complex scientific phenomenon which can be used as a model to examine students' conceptual understanding in science. Primary student-teachers' understanding of global environmental problems, such as climate change and ozone depletion, indicates that they have many misconceptions. The present mixed method study examines Finnish primary student-teachers' understanding of the greenhouse effect based on the results obtained via open-ended and closed-form questionnaires. The open-ended questionnaire considers primary student-teachers' spontaneous ideas about the greenhouse effect depicted by concept maps. The present study also uses statistical analysis to reveal respondents' conceptualization of the greenhouse effect. The concept maps and statistical analysis reveal that the primary student-teachers' factual knowledge and their conceptual understanding of the greenhouse effect are incomplete and even misleading. In the light of the results of the present study, proposals for modifying the instruction of climate change in science, especially in geography, are presented.

Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

International Nuclear Information System (INIS)

Noguchi, M.; Ogasawara, M.; Iwabuchi, K.; Osgasawara, K.; Ishihara, T.; Good, R.A.; Morikawa, K.; Onoe, K.

1985-01-01

The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

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

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.

Treatment of non-vital primary molar using lesion sterilization and tissue repair (LSTR 3Mix-MP

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Tania Saskianti

2013-06-01

Full Text Available Background: Root canal preparation and anatomic variations of deciduous teeth often cause the child patient uncooperative and sometimes the treatment failure. the non-threatening treatment and non-invasive approaches is needed to obtain a good cooperation from child patient. Purpose: The study was aimed to clinically evaluate the use of 3Mix-MP- a combination of antibacterial drugs, i.e. metronidazole, minocycline and ciprofloxacin (3Mix, and macrogol and propylene glycol (MP - as pulp medicament on a necroses primary molar. Methods: Subject were the children patients of Pediatric Dental Clinic Universitas Airlangga Dental Hospital. Eight primary molars with pulp necroses due to dental caries were selected as samples. The treatment was done based on the concept of lesion sterilization and tissue repair (LSTR therapy. A slice of 3 Mix-MP pastes was placed in the cavity and then sealed with glassionomer cement. Subjects were asked for recall visit in 1, 3 and 6 months post treatment, for clinical and radiographic evaluation. The antibacterial effect of 3 Mix-MP was compared with tempophore on mixed bacteria of pulp cavity which was isolated prior to therapy. The antibacterial effect was determined by measuring the inhibition zone after 24 hours anaerobe incubation. Results: Seven out of 8 subjects on recall visit showed no acute or chronic clinical symptoms, such as fistulae, abscess, purulent exudates, swelling or feel any pain during mastication. Microbiological test result showed LSTR 3Mix-MP had antibacterial effect higher than tempophore (p<0.001. Conclusion: The study revealed that 3Mix-MP treatment showed clinical and radiographic positive response on necrose primary molar.Latar belakang: Preparasi saluran akar dan variasi anatomi gigi sulung seringkali menyebabkan pasien anak tidak kooperatif dan kadang menyebabkan kegagalan perawatan. Perawatan yang tidak menakutkan dan non-invasif diperlukan untuk mendapatkan kerjasama yang baik dari

Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission.

Science.gov (United States)

Yao, Jianfeng; Zhang, Guixin; Liang, Chen; Li, Gang; Chen, Xin; Ma, Qiaoling; Zhai, Weihua; Yang, Donglin; He, Yi; Jiang, Erlie; Feng, Sizhou; Han, Mingzhe

2017-04-01

Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRD neg after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario. Copyright © 2017 Elsevier Ltd. All rights reserved.

Primary oral and nasal transmissible venereal tumor in a mix-breed dog

OpenAIRE

Rezaei, Mahdieh; Azizi, Shahrzad; Shahheidaripour, Shima; Rostami, Sara

2016-01-01

Transmissible venereal tumor (TVT) is a coitally transmitted tumor of dogs with widespread distribution. The present study describes the occurrence of the primary oral and nasal TVT in a 10-year-old, female, mix-breed dog. The case was presented with a history of anorexia, inability to swallow and dyspnea. Clinical examinations revealed the emaciation, muzzle deformity due to the presence of a friable, fleshy, cauliflower-like mass in the oral cavity and submandibular lymphadenopathy. TVT was...

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....

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.

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.

Successful Reduced Intensity Allogeneic Transplant With Full Donor Chimerism and Good Quality of Life in Adolescent Patient With Wiskott-Aldrich Syndrome.

Science.gov (United States)

Ali, Salah; Gacsadi, Anna; McDougall, Elizabeth; Armstrong, Christine; Krueger, Joerg; Schechter, Tal; Ali, Muhammad

2017-07-01

Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema, immune deficiency, and autoimmune phenomena. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Myeloablative conditioning is the most common regimen used for HSCT in patients with WAS to avoid the risk of mixed donor chimerism and autoimmunity post-HSCT. There is limited data on the use of reduced intensity conditioning for HSCT in patients with WAS. Here, we report a case with severe phenotype of WAS transplanted successfully with reduced intensity conditioning, which is an acceptable conditioning regimen and can be considered in patients with WAS with significantly impaired organ functions.

Progressive changes in arch width from primary to early mixed dentition period: a longitudinal study.

Science.gov (United States)

Sangwan, S; Chawla, H S; Goyal, A; Gauba, K; Mohanty, U

2011-01-01

The present study was conducted to evaluate, on a longitudinal basis, the changes in intercanine and intermolar widths form the primary to the early mixed dentition periods. A total of 38 children aged 4-5 years, with normal occlusion without any proximal caries or any dental anomalies, were selected. The impressions were recorded and casts were prepared. Intercanine and intermolar widths were measured on these dental casts with the help of a digital vernier calliper. After 3 years follow-up, the impressions were recorded again and dental casts were prepared. Intercanine and intermolar widths were measured again at this stage and were compared with the baseline data using the paired t-test and the chi square test. There is a significant increase in the intercanine (3.93 + 1.70 mm) and intermolar width (1.49 + 1.77 mm) during the transition period from primary to early mixed dentition in both the arches and both the sexes. The gender-wise comparison showed a greater increase in males than in females, but this was not statistically significant. A thorough knowledge of growth changes during various stages of the mixed dentition period are important for a pediatric dentist to make an accurate diagnosis and treatment planning during preventive and interceptive orthodontics.

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...

Langerhans cells from human oral epithelium are more effective at stimulating allogeneic T cells in vitro than Langerhans cells from skin.

Science.gov (United States)

Hasséus, B; Jontell, M; Bergenholtz, G; Dahlgren, U I

2004-06-01

This report is focused on the functional capacity of Langerhans cells (LC) in the epithelium of skin and oral mucosa, which both meet different antigenic challenges. The capacity of LC from human oral and skin epithelium to provide co-stimulatory signals to T cells in vitro was compared. LC in a crude suspension of oral epithelial cells had a significantly enhanced T cell co-stimulatory capacity compared to skin epithelial cells. This applied both to cultures with concanavalin A (con-A)-stimulated syngeneic T cells and to a mixed epithelial cell lymphocyte reaction involving allogeneic T cells. The co-stimulatory capacity of oral and skin epithelial cells was reduced by >70% if monoclonal antibodies against HLA-DR, -DP and -DQ were added to the cultures with allogeneic T cells, indicating the involvement of HLA class II expressing LC. Immunohistochemistry revealed that 6% of the epithelial cells were CD1a + LC in sections from both oral and skin epithelium. Interleukin (IL)-8 production was higher in cultures of oral epithelial cells and con-A stimulated T cells than in corresponding cultures with skin epithelial cells as accessory cells. The results suggest that LC in human oral epithelium are more efficient at stimulating T cells than those of skin.

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.

Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

International Nuclear Information System (INIS)

Onoe, K.; Yasumizu, R.; Oh-Ishi, T.; Kakinuma, M.; Good, R.A.; Morikawa, K.

1981-01-01

Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient

Transplantation of Allogeneic PW1pos/Pax7neg Interstitial Cells Enhance Endogenous Repair of Injured Porcine Skeletal Muscle

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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.

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

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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

Splenocytes cultured in low concentrations of IL-2 generate NK cell specificities toward syngenic and allogenic targets

DEFF Research Database (Denmark)

Nissen, Mogens Holst; Jeppesen, M; Claesson, M H

2000-01-01

Splenocytes cultured in the presence of 30-60 units/ml IL-2 for 5 days develop natural killer activity toward syngeneic and allogeneic tumor cell targets. The IL-2 activated splenocytes, themselves, are partially resistant, whereas concanavalin A-activated T blast cells are completely resistant...... to killing. Surprisingly, major histocompatibility complex (MHC)-I-negative target cells are also resistant to natural killer (NK)-cell-mediated killing. Cells resistant to killing were unable to block NK-cell-mediated killing of sensitive targets as judged from cold target cell inhibition experiments......, and one type of target cells sensitive to killing did generally not cross-block killing of other killing-sensitive target cell types. Alloantigen exposure of splenocytes, i.e., one-way mixed lymphocyte cultures, partially prevents the development of NK-cell activity. Our data suggest that target...

Social Orders and Interactions among Children in Age-Mixed Classes in Primary Schools--New Perspectives from a Synthesis of Ethnographic Data

Science.gov (United States)

Huf, Christina; Raggl, Andrea

2015-01-01

The article synthesises data from two ethnographic projects, which both explore interactions of children in age-mixed groups in primary schools. It illuminates critical perspectives on social orders and children's interactions in age-mixed classes by showing how pupils in age-mixed groups become involved in power relations and how the teacher's…

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.

Turbulent Mixing of Primary and Secondary Flow Streams in a Rocket-Based Combined Cycle Engine

Science.gov (United States)

Cramer, J. M.; Greene, M. U.; Pal, S.; Santoro, R. J.; Turner, Jim (Technical Monitor)

2002-01-01

This viewgraph presentation gives an overview of the turbulent mixing of primary and secondary flow streams in a rocket-based combined cycle (RBCC) engine. A significant RBCC ejector mode database has been generated, detailing single and twin thruster configurations and global and local measurements. On-going analysis and correlation efforts include Marshall Space Flight Center computational fluid dynamics modeling and turbulent shear layer analysis. Potential follow-on activities include detailed measurements of air flow static pressure and velocity profiles, investigations into other thruster spacing configurations, performing a fundamental shear layer mixing study, and demonstrating single-shot Raman measurements.

Preliminary study of the primary nozzle position of a supersonic air ejector with a constant-area mixing chamber

Directory of Open Access Journals (Sweden)

Kracik Jan

2017-01-01

Full Text Available This work aims at investigating the primary nozzle position in a proposed supersonic air ejector device. The ejector is primarily made up of a supersonic primary nozzle, which is located in the axis of the ejector, a suction chamber or secondary stream inlet, a mixing chamber and a diffuser. The ejector design allows to translate the primary nozzle in the axis direction and fix it in a chosen distance from the beginning of the mixing chamber and hence influence the secondary mass flow rate. In a limit case, it is possible to set the nozzle to such a position where no secondary flow occurs. If we ignore the case where no secondary flow occurs, five different nozzle distances have been investigated in this paper. Some cases seem to be alike and there are no significant dissimilarities between them. Courses of relative back-pressure ratio are carried out against the entrainment ratio and transition between on-design and off-design regimes is determined. Measurements of the mixed flow based on the standard ISO 5167 are performed by means of orifice plate method. In addition, a comparison between experiments and simulations performed by Ansys Fluent software is presented in order to indicate further improvements to the numerical model.

Preliminary results of lab-scale investigations of products of incomplete combustion during incineration of primary and mixed digested sludge.

Science.gov (United States)

Braguglia, C M; Bagnuolo, G; Gianico, A; Mininni, G; Pastore, C; Mascolo, G

2016-03-01

Separation between primary and secondary sludge treatment could be a valuable solution for sludge management. According to this approach, secondary sludge can be conveniently used in agriculture while primary sludge could be easily dried and incinerated. It follows that some concern may arise from incinerating primary sludge with respect to the current practice to incinerate mixed digested sludge. Incineration of primary and mixed digested municipal sludge was investigated with a lab-scale equipment in terms of emissions of products of incomplete combustion (PICs) during incineration failure modes. PICs can be grouped in three sub-categories, namely aliphatic hydrocarbons (alkanes and alkenes), compounds with a single aromatic ring, and polycyclic aromatic hydrocarbons (PAHs). After-burning temperature was the most important parameter to be controlled in order to minimize emissions of alkanes and alkenes. As for mono-aromatic compounds, benzene and toluene are the most thermally resistant compounds, and in some cases, an after-burning temperature of 1100 °C was not enough to get the complete destruction of benzene leading to a residual emission of 18 mg/kgsludge. PAHs showed an opposite trend with respect to aliphatic and mono-aromatic hydrocarbons being the thermal failure mode the main responsible of PIC emissions. A proper oxygen concentration is more important than elevated temperature thus reflecting the high thermal stability of PAHs. Overall, obtained results, even though obtained under flameless conditions that are different from those of the industrial plants, demonstrated that separation of primary and secondary sludge does not pose any drawbacks or concern regarding primary sludge being disposed of by incineration even though it is more contaminated than mixed digested sludge in terms of organic pollutants.

Progressive changes in arch width from primary to early mixed dentition period: A longitudinal study

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S Sangwan

2011-01-01

Full Text Available Objective: The present study was conducted to evaluate, on a longitudinal basis, the changes in intercanine and intermolar widths form the primary to the early mixed dentition periods. Materials and Methods: A total of 38 children aged 4-5 years, with normal occlusion without any proximal caries or any dental anomalies, were selected. The impressions were recorded and casts were prepared. Intercanine and intermolar widths were measured on these dental casts with the help of a digital vernier calliper. After 3 years follow-up, the impressions were recorded again and dental casts were prepared. Intercanine and intermolar widths were measured again at this stage and were compared with the baseline data using the paired t-test and the chi square test. Results: There is a significant increase in the intercanine (3.93 + 1.70 mm and intermolar width (1.49 + 1.77 mm during the transition period from primary to early mixed dentition in both the arches and both the sexes. The gender-wise comparison showed a greater increase in males than in females, but this was not statistically significant. Conclusion: A thorough knowledge of growth changes during various stages of the mixed dentition period are important for a pediatric dentist to make an accurate diagnosis and treatment planning during preventive and interceptive orthodontics.

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.)

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....

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

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.

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

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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.

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.

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

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

Connecting the dots and merging meaning: using mixed methods to study primary care delivery transformation.

Science.gov (United States)

Scammon, Debra L; Tomoaia-Cotisel, Andrada; Day, Rachel L; Day, Julie; Kim, Jaewhan; Waitzman, Norman J; Farrell, Timothy W; Magill, Michael K

2013-12-01

To demonstrate the value of mixed methods in the study of practice transformation and illustrate procedures for connecting methods and for merging findings to enhance the meaning derived. An integrated network of university-owned, primary care practices at the University of Utah (Community Clinics or CCs). CC has adopted Care by Design, its version of the Patient Centered Medical Home. Convergent case study mixed methods design. Analysis of archival documents, internal operational reports, in-clinic observations, chart audits, surveys, semistructured interviews, focus groups, Centers for Medicare and Medicaid Services database, and the Utah All Payer Claims Database. Each data source enriched our understanding of the change process and understanding of reasons that certain changes were more difficult than others both in general and for particular clinics. Mixed methods enabled generation and testing of hypotheses about change and led to a comprehensive understanding of practice change. Mixed methods are useful in studying practice transformation. Challenges exist but can be overcome with careful planning and persistence. © Health Research and Educational Trust.

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...

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...

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.

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

Intravenous versus topical tranexamic acid administration in primary total knee arthroplasty: a meta-analysis.

Science.gov (United States)

Shin, Young-Soo; Yoon, Jung-Ro; Lee, Hoon-Nyun; Park, Se-Hwan; Lee, Dae-Hee

2017-11-01

This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in haemoglobin levels. Studies were included in this meta-analysis to check whether they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in haemoglobin levels before and after surgery in primary TKA with TXA administered through both the IV and topical routes. Ten studies were included in this meta-analysis. The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95 % CI 0.63-2.81; n.s.) and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95 % CI 0.41 to 1.77; n.s.) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95 % CI -50.74 to 185.66 mL; n.s.), 52.1 mL greater estimated blood loss (95 % CI -155.27 to 51.03 mL; n.s.), and 51.4 mL greater total blood loss (95 % CI -208.16 to 105.31 mL; n.s.) in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in haemoglobin levels (0.02 g/dL, 95 % CI -0.36 to 0.39 g/dL; n.s.). In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in haemoglobin levels between the IV and topical administration of TXA. In addition, results from subgroup analysis evaluating the effect of the times of TXA administration through the IV route suggested that double IV dose of TXA is more effective than single dose in terms of the

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

Alloreactive regulatory T cells allow the generation of mixed chimerism and transplant tolerance

Directory of Open Access Journals (Sweden)

Paulina eRuiz

2015-11-01

Full Text Available The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant protocol using retinoic acid induced alloantigen-specific Tregs, clinically available immunosuppressive drugs and lower doses of irradiation. We demonstrate that retinoic acid induced alloantigen-specific Tregs in addition to a non-myeloablative bone-marrow transplant protocol generates stable mixed chimerism and induce tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

Science.gov (United States)

Sohn, Sang Kyun; Moon, Joon Ho

2015-08-01

According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Allogeneic stem cell transplantation in acute myeloid leukemia

Directory of Open Access Journals (Sweden)

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%.

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.

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.

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

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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.

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

OpenAIRE

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

2009-01-01

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 w...

Anti-Donor Immune Responses Elicited by Allogeneic Mesenchymal Stem Cells and Their Extracellular Vesicles: Are We Still Learning?

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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.

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

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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.□

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.

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.

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...

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

Screening mixed depression and bipolarity in the postpartum period at a primary health care center.

Science.gov (United States)

Çelik, Sercan Bulut; Bucaktepe, Gamze Erten; Uludağ, Ayşegül; Bulut, İbrahim Umud; Erdem, Özgür; Altınbaş, Kürşat

2016-11-01

Mixed depression is a clinical condition accompanied by the symptoms of (hypo)mania and is considered to be a predictor for bipolar disorder. Compared to pure major depression, mixed depression is worse in progress. There are limited data on the prevalence of mixed depression since it is a relatively new entity. Therefore, the present study aimed to investigate the prevalence of mixed depression during the postpartum period which is risky for mood disorders. The study included 63 postpartum women. The participants were administered Beck Depression Scale, Edinburgh Postnatal Depression Scale (EPDS), Mood Disorders Questionnaire (MDQ), and Modified Hypomania Symptom Checklist-32 (mHCL-32). The MDQ scores of the women with expected depression according to the EPDS cut-off scores, were significantly higher than the women with lower EPDS scores (t=-4.968; pdepression scores compared to the women under EPDS cut-off scores (t=-4.713; pdepression, respectively. In addition, 3 (4.8%) women require additional clinical examination for bipolar disorder. The scores for the first item of MDQ were above the cut-off value in 11 (17.5%) women. According to the mHCL-32 results, 50 (79.4%) women had at least 1 symptom, 45 (71.4%) women had at least 3 symptoms, and 43 (68.3%) women had at least 5 symptoms of mixed depression. Postpartum mixed depression should be promptly diagnosed by using appropriate diagnostic tools, particularly by primary health care physicians. Patients with mixed depression should be closely monitored to avoid manic switch. Copyright © 2016 Elsevier Inc. All rights reserved.

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....

Is there a role for B lymphocyte chimerism in the monitoring of B-acute lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?

Directory of Open Access Journals (Sweden)

Yi-Ning Yang

2015-03-01

Full Text Available Objective: To determine the sensitivity and significance of B-cell chimerism for the detection of early engraftment, transplant rejection, and disease relapse. Methods: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK cells was made in 20 B-cell acute lymphoblastic leukemia (B-ALL patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT. In the early period after allo-HSCT, the latest establishment of B-cell complete chimerism (CC was observed in a majority of patients. Results: The percentage of donor cells of B-cell lineage was lower than the percent of T-cell lineage in most of the mixed chimerism (MC patients. During graft rejection, the frequency of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and 2/5. When disease relapsed, five patients showed a faster decrease of the donor percent of B-cells than of T- or NK-cells. Only one patient displayed a more rapid decrease in NK-cells than in T- or B-cells. Conclusion: Monitoring of B-cell chimerism after HSCT seems to be valuable for insuring complete engraftment, anticipating graft rejection, and relapse in B-ALL patients. Keywords: B cell acute lymphoblastic leukemia (B-ALL, B-cell, T-cell, Chimerism, Allogeneic hematopoietic stem cell transplantation (allo-HSCT

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.

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

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)

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.

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.

ERIC/EECE Report. Mixed Age Grouping.

Science.gov (United States)

Cesarone, Bernard

1995-01-01

Summarizes eight recent ERIC documents and seven journal articles on mixed-age grouping. Includes discussions of teaching in the multiage classroom, Kentucky's Primary Program, developmentally appropriate practices in the primary grades, thematic instruction, attitudes toward mixed-age grouping, and questions and answers about mixed-age grouping.…

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

Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2.

Science.gov (United States)

Cui, Lei; Yin, Shuo; Liu, Wei; Li, Ningli; Zhang, Wenjie; Cao, Yilin

2007-06-01

Multipotent mesenchymal stem cells (MSCs) in adult tissue are known to be less immunogenic and immunosuppressive. Previous study showed that primary cultures of human adipose-derived stem cells (ADSCs) shared their immunomodulatory properties with other MSCs. However, whether passaged human ADSCs can retain their immunomodulatory effect after in vitro expansion remains unknown. In addition, the mechanism of ADSC-mediated immunomodulatory effect remains to be elucidated. This study aimed to investigate these issues by using passaged human ADSCs as an in vitro study model. Flow cytometry showed that passaged ADSCs expressed human leukocyte antigen (HLA) class I but not class II molecules, which could be induced to express to a high level with interferon-gamma (IFN-gamma) treatment. The study found that passaged ADSCs could not elicit lymphocyte proliferation after co-culturing with them, even after IFN-gamma treatment. In addition, either IFN-gamma-treated or non-treated ADSCs could inhibit phytohemagglutinin (PHA)-stimulated lymphocyte proliferation. Moreover, passaged ADSCs could serve as the third-party cells to inhibited two-way mixed lymphocyte reaction (MLR). Further study using a transwell system also showed that this type of immunosuppressive effect was not cell-cell contact dependent. In defining possible soluble factors, we found that passaged ADSCs significantly increased their secretion of prostaglandin E2 (PGE2), but not transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF), when they were co-cultured with MLR. Furthermore, the result demonstrated that only PGE2 production inhibitor indomethacine, but not TGF-beta- and HGF-neutralizing antibodies, could significantly counteract ADSC-mediated suppression on allogeneic lymphocyte proliferation. These results indicated that in vitro expanded ADSCs retain low immunogenicity and immunosuppressive effect, and PGE2 might be the major soluble factor involved in the in vitro inhibition of

Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

International Nuclear Information System (INIS)

Pierpaoli, W.; Maestroni, G.J.M.

1983-01-01

Allogeneic, H-2-incompatible irradiation chimeras (H-2sup(d) → H-2sup(b)) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immuno-competent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease, and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism. (Auth.)

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.

Patient reported outcomes in view of symptom experience of late effects and self-management of adult long-term survivors after allogeneic haematopoietic stem cell transplantation - a mixed methods study

OpenAIRE

Kirsch, Monika

2014-01-01

Even years after allogeneic stem cell transplantation, recipients face a continuing risk of developing serious late effects. Previous studies have focused on the pathophysiological understanding of late effects, as well as on treatment and disease-related prediction of long-term post-transplant complications. In recent years, patient-reported outcomes (PROs) have been recognized as an invaluable source of information on the evolution of patients’ conditions. To date, however, few studies have...

Donor-specific Anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation

Directory of Open Access Journals (Sweden)

Sarah Morin-Zorman

2016-08-01

Full Text Available Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT is a curative treatment for a wide variety of hematological diseases. In 30% of the cases, a geno-identical donor is available. Any other situation displays some level of Human Leukocyte Antigen (HLA incompatibility between donor and recipient. Deleterious effects of anti-HLA immunization have long been recognized in solid organ transplant recipients. More recently, anti-HLA immunization was shown to increase the risk of Primary Graft Failure (PGF, a severe complication of AHSCT that occurs in 3 to 4% of matched unrelated donor transplantation and up to 15% in cord blood transplantation and T-cell depleted haplo-identical stem cell transplantation. Rates of PGF in patients with DSA were reported to be between 24 to 83% with the highest rates in haplo-identical and cord blood transplantation recipients. This led to the recommendation of anti-HLA antibody screening to detect Donor Specific Antibodies (DSA in recipients prior to AHSCT. In this review, we highlight the role of anti-HLA antibodies in AHSCT and the mechanisms that may lead to PGF in patients with DSA, and discuss current issues in the field.

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...

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.

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

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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.

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)

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

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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.

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...

Outcomes of allogeneic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria with or without aplastic anemia.

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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.

Central nervous system infection following allogeneic hematopoietic stem cell transplantation.

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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.

Seasonal variability of mixed layer in the central Arabian Sea and its implication on nutrients and primary productivity

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PrasannaKumar, S.; Narvekar, J.

-1 Seasonal variability of mixed layer in the central Arabian Sea and its implication on nutrients and primary productivity S. Prasanna Kumar and Jayu Narvekar National Institute of Oceanography, Dona Paula, Goa-403 004, India... on a 2? x 4? grids up to a depth of 500m. Monthly mean temperature and salinity data were used to calculate the sigma-t values (UNESCO, 1981). We also used nitrate, chlorophyll a and primary productivity data in the upper 120m water column...

Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

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Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

2015-03-01

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

Do autologous blood transfusion systems reduce allogeneic blood transfusion in total knee arthroplasty?

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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.

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

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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.

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

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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...

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

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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.

Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients.

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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.

Complications of allogeneic hematopoietic stem cell transplantation.

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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.

The impact of case mix on timely access to appointments in a primary care group practice.

Science.gov (United States)

Ozen, Asli; Balasubramanian, Hari

2013-06-01

At the heart of the practice of primary care is the concept of a physician panel. A panel refers to the set of patients for whose long term, holistic care the physician is responsible. A physician's appointment burden is determined by the size and composition of the panel. Size refers to the number of patients in the panel while composition refers to the case-mix, or the type of patients (older versus younger, healthy versus chronic patients), in the panel. In this paper, we quantify the impact of the size and case-mix on the ability of a multi-provider practice to provide adequate access to its empanelled patients. We use overflow frequency, or the probability that the demand exceeds the capacity, as a measure of access. We formulate problem of minimizing the maximum overflow for a multi-physician practice as a non-linear integer programming problem and establish structural insights that enable us to create simple yet near optimal heuristic strategies to change panels. This optimization framework helps a practice: (1) quantify the imbalances across physicians due to the variation in case mix and panel size, and the resulting effect on access; and (2) determine how panels can be altered in the least disruptive way to improve access. We illustrate our methodology using four test practices created using patient level data from the primary care practice at Mayo Clinic, Rochester, Minnesota. An important advantage of our approach is that it can be implemented in an Excel Spreadsheet and used for aggregate level planning and panel management decisions.

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...

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

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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

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.

Guidance for deciding upon use of primary mixed methods studies in research synthesis : Lessons learned in childhood trauma

NARCIS (Netherlands)

Boeije, H.; van Wesel, F.; Slagt, M.

2014-01-01

When reviewing literature, mixed methods studies (MMS) are increasingly retrieved, yet it is unclear how they should be dealt with in a research synthesis. In this article we examine the inclusion of primary MMS in research synthesis, based on experiences with a meta-analysis (MA) and a qualitative

Guidance for deciding upon use of primary mixed methods studies in research synthesis: lessons learned in childhood trauma

NARCIS (Netherlands)

Boeije, H.R.; van Wesel, F.; Slagt, M.I.

2014-01-01

When reviewing literature, mixed methods studies (MMS) are increasingly retrieved, yet it is unclear how they should be dealt with in a research synthesis. In this article we examine the inclusion of primary MMS in research synthesis, based on experiences with a meta-analysis (MA) and a qualitative

Guidance for deciding upon use of primary mixed methods studies in research synthesis: lessons learned in childhood trauma.

NARCIS (Netherlands)

Boeije, H.; Wesel, F. van; Slagt, M.

2014-01-01

When reviewing literature, mixed methods studies (MMS) are increasingly retrieved, yet it is unclear how they should be dealt with in a research synthesis. In this article we examine the inclusion of primary MMS in research synthesis, based on experiences with a meta-analysis (MA) and a qualitative

Progressive changes in arch width from primary to early mixed dentition period: A longitudinal study

OpenAIRE

S Sangwan; H S Chawla; A Goyal; K Gauba; U Mohanty

2011-01-01

Objective: The present study was conducted to evaluate, on a longitudinal basis, the changes in intercanine and intermolar widths form the primary to the early mixed dentition periods. Materials and Methods: A total of 38 children aged 4-5 years, with normal occlusion without any proximal caries or any dental anomalies, were selected. The impressions were recorded and casts were prepared. Intercanine and intermolar widths were measured on these dental casts with the help of a digital vernier ...

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.

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.

Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.

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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

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...

Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft

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Francesco Saverio De Ponte

2017-02-01

Full Text Available A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla.

АВ0-INCOMPATIBILITY IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: 15-YEARS EXPERIENCE OF R.M. GORBACHEVA MEMORIAL RESEARCH INSTITUTE FOR CHILDREN ONCOLOGY, HEMATOLOGY AND TRANSPLANTATION

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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.

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...

Primary oral and nasal transmissible venereal tumor in a mix-breed dog

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Mahdieh Rezaei

2016-05-01

Full Text Available Transmissible venereal tumor (TVT is a coitally transmitted tumor of dogs with widespread distribution. The present study describes the occurrence of the primary oral and nasal TVT in a 10-year-old, female, mix-breed dog. The case was presented with a history of anorexia, inability to swallow and dyspnea. Clinical examinations revealed the emaciation, muzzle deformity due to the presence of a friable, fleshy, cauliflower-like mass in the oral cavity and submandibular lymphadenopathy. TVT was diagnosed based on histopathological findings. The dog was discharged with therapeutic intervention with vincristine. Unfortunately, the case died before readmission because of the progressive worsening of the general condition. Our findings highlight the need for considering TVT for the differential diagnosis of the extragenital masses in dogs.

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

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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.

Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study

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A. Marmotti

2017-01-01

Full Text Available Umbilical cord (UC may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.

Frozen allogeneic human epidermal cultured sheets for the cure of complicated leg ulcers.

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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.

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

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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

Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

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Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

2018-04-01

Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol.

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Jauregui, Amale; Ponte, Joaquín; Salgueiro, Monika; Unanue, Saloa; Donaire, Carmen; Gómez, Maria Cruz; Burgos-Alonso, Natalia; Grandes, Gonzalo

2015-03-20

In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions

Disease-specific clinical pathways - are they feasible in primary care? A mixed-methods study.

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Grimsmo, Anders; Løhre, Audhild; Røsstad, Tove; Gjerde, Ingunn; Heiberg, Ina; Steinsbekk, Aslak

2018-04-12

To explore the feasibility of disease-specific clinical pathways when used in primary care. A mixed-method sequential exploratory design was used. First, merging and exploring quality interview data across two cases of collaboration between the specialist care and primary care on the introduction of clinical pathways for four selected chronic diseases. Secondly, using quantitative data covering a population of 214,700 to validate and test hypothesis derived from the qualitative findings. Primary care and specialist care collaborating to manage care coordination. Primary-care representatives expressed that their patients often have complex health and social needs that clinical pathways guidelines seldom consider. The representatives experienced that COPD, heart failure, stroke and hip fracture, frequently seen in hospitals, appear in low numbers in primary care. The quantitative study confirmed the extensive complexity among home healthcare nursing patients and demonstrated that, for each of the four selected diagnoses, a homecare nurse on average is responsible for preparing reception of the patient at home after discharge from hospital, less often than every other year. The feasibility of disease-specific pathways in primary care is limited, both from a clinical and organisational perspective, for patients with complex needs. The low prevalence in primary care of patients with important chronic conditions, needing coordinated care after hospital discharge, constricts transferring tasks from specialist care. Generic clinical pathways are likely to be more feasible and efficient for patients in this setting. Key points Clinical pathways in hospitals apply to single-disease guidelines, while more than 90% of the patients discharged to community health care for follow-up have multimorbidity. Primary care has to manage the health care of the patient holistically, with all his or her complex needs. Patients most frequently admitted to hospitals, i.e. patients with COPD

RENAL ALLOGENEIC TRANSPLANTATION IN PATIENT WITH HAEMOPHILIA B

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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.

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

The impact of virus population diversity on the dynamics of cytomegalovirus DNAemia in allogeneic stem cell transplant recipients.

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Vinuesa, Víctor; Bracho, María Alma; Albert, Eliseo; Solano, Carlos; Torres-Puente, Manuela; Giménez, Estela; González-Candelas, Fernando; Navarro, David

2017-10-01

Mixed cytomegalovirus (CMV) infections are associated with delayed viral clearance in solid organ transplant recipients. We investigated whether this could be extrapolated to allogeneic stem cell transplant (allo-SCT) recipients. A total of 48 plasma specimens, obtained during 29 episodes of active CMV infection in 25 non-consecutive allo-SCT patients, were analysed. Baseline blood specimens, drawn shortly prior to the inception of pre-emptive antiviral therapy (pre-treatment specimen; n=29), as well as follow-up samples obtained either after the initiation of antiviral therapy (post-treatment specimen; n=15) or during recurrent episodes (n=4) were analysed. Plasma CMV DNA loads were quantified by real-time PCR and the CMV genotyping was performed by ultra-deep sequencing of hypervariable regions in the genes coding for glycoproteins N (gN) and O (gO). A trend towards higher CMV DNA peak loads, longer CMV DNAemia episode durations and slower CMV DNAemia decay rates was observed for episodes with mixed CMV genotype populations compared to those caused by single CMV variants, although the differences did not reach statistical significance. The length of the treatment course required to clear DNAemia was significantly longer in these mixed episodes (P=0.002). Significant changes in the number or frequency of CMV gN or gO genetic variants were documented following the initiation of antiviral therapy or in recurrent episodes. CMV diversity may have a major impact on the kinetics of CMV DNAemia clearance during the treatment of active CMV infection episodes in allo-SCT recipients.

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

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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.

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...

Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

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Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

2015-04-15

Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis.

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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.

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

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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.

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

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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...

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

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

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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

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

Histomorhological and clinical evaluation of maxillary alveolar ridge reconstruction after craniofacial trauma by applying combination of allogeneic and autogenous bone graft.

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De Ponte, Francesco Saverio; Falzea, Roberto; Runci, Michele; Siniscalchi, Enrico Nastro; Lauritano, Floriana; Bramanti, Ennio; Cervino, Gabriele; Cicciu, Marco

2017-02-01

A variety of techniques and materials for the rehabilitation and reconstruction of traumatized maxillary ridges prior to dental implants placement have been described in literature. Autogenous bone grafting is considered ideal by many researchers and it still remains the most predictable and documented method. The aim of this report is to underline the effectiveness of using allogeneic bone graft for managing maxillofacial trauma. A case of a 30-year-old male with severely atrophic maxillary ridge as a consequence of complex craniofacial injury is presented here. Augmentation procedure in two stages was performed using allogeneic and autogenous bone grafts in different areas of the osseous defect. Four months after grafting, during the implants placement surgery, samples of both sectors were withdrawn and submitted to histological evaluation. On the examination of the specimens, treated by hematoxylin and eosin staining, the morphology of integrated allogeneic bone grafts was revealed to be similar to the autologous bone. Our clinical experience shows how the allogeneic bone graft presented normal bone tissue architecture and is highly vascularized, and it can be used for reconstruction of severe trauma of the maxilla. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Administrative Stressors and Islamic Coping Strategies Among Muslim Primary Principals in Malaysia: A Mixed Method Study.

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Tahir, Lokman Mohd; Khan, Aqeel; Musah, Mohammed Borhandden; Ahmad, Roslee; Daud, Khadijah; Al-Hudawi, Shafeeq Hussain Vazhathodi; Musta'Amal, Aede Hatib; Talib, Rohaya

2017-11-18

Principals are school leaders who experienced stress while leading their schools towards excellence. However, principals stress experiences are always ignored and least studied. This mixed-methods study investigates primary principals' stress experiences and their Islamic coping strategies used in incapacitating the stress experiences. A total of 216 Muslim primary principals across different gender, types of schools and years of experiences as school leaders responded to the administrative stress and the Islamic coping strategies items. In addition, seven primary principals were purposefully selected and interviewed in exploring their reasons of using Islamic coping strategies for their relieving process. Results discovered that primary principals experienced fairly stress level and they perceived managing students' academic achievement was the most stressor followed by managing teachers' capabilities. Although findings revealed that no significant differences in terms primary principals' demographics; male primary principals, and experienced between 6 and 10 years and positioned in schools with least students (SLS) category have slightly higher level of stress. In terms of Islamic coping strategies used by primary principals, saying dhua to Allah, performing dhikir and reciting the Yassen are selected coping approaches employed in handling their stress. From interviews, primary principals also revealed that they used Islamic religious approaches as part of meaningful activities not just to overcoming their stress but also as part of religious approaches in remembering Allah, thinking back their past mistakes as part of the Muhasabah process. Therefore, we believed that religious approaches should be taken into consideration in principals' training as it provides peaceful and treatment in managing principals' stress issue.

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

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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.

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

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

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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

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

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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.

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

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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.

Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

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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.

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.

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

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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.

Heterogenous populations of cytotoxic cells in the peritoneal cavity of BALB/c mice immunized with allogeneic EL4 leukemia cells

International Nuclear Information System (INIS)

Zighelboim, J.; Bonavida, B.; Fahey, J.L.

1974-01-01

Adherent cells, presumably macrophages, obtained from the peritoneal cavity shortly after rejection of the allogeneic leukemia EL4, produced effective cell-mediated cytotoxicity (CMC) in vitro. These cytotoxic cells were sensitive to anti-macrophage serum and resistant to anti-thymocyte serum and 10,000 roentgen irradiation. In contrast, a second population of specifically cytotoxic cells were nonadherent, sensitive to x-rays and anti-thymocyte serum, but not to anti-macrophage serum. The two cell populations had a cooperative cytotoxic effect in vitro against allogeneic tumor cells

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

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

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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.

Reduced use of allogeneic platelets through high-yield perioperative autologous plateletpheresis and reinfusion.

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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.

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

Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid Leukemia.

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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.

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.

The challenges of meeting the blood transfusion requirements in Sub-Saharan Africa: the need for the development of alternatives to allogenic blood.

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Osaro, Erhabor; Charles, Adias Teddy

2011-01-01

As a resource, allogenic blood has never been more in demand than it is today. Escalating elective surgery, shortages arising from a fall in supply, a lack of national blood transfusion services, policies, appropriate infrastructure, trained personnel, and financial resources to support the running of a voluntary nonremunerated donor transfusion service, and old and emerging threats of transfusion-transmitted infection, have all conspired to ensure that allogenic blood remains very much a vital but limited asset to healthcare delivery particularly in Sub-Saharan Africa. This is further aggravated by the predominance of family replacement and commercially remunerated blood donors, rather than regular benevolent, nonremunerated donors who give blood out of altruism. The demand for blood transfusion is high in Sub-Saharan Africa because of the high prevalence of anemia especially due to malaria and pregnancy-related complications. All stakeholders in blood transfusion have a significant challenge to apply the best available evidenced-based medical practices to the world-class management of this precious product in a bid to using blood more appropriately. Physicians in Sub-Saharan Africa must always keep in mind that the first and foremost strategy to avoid transfusion of allogenic blood is their thorough understanding of the pathophysiologic mechanisms involved in anemia and coagulopathy, and their thoughtful adherence to the evidenced-based good practices used in the developed world in a bid to potentially reduce the likelihood of allogenic blood transfusion in many patient groups. There is an urgent need to develop innovative ways to recruit and retain voluntary low-risk blood donors. Concerns about adverse effects of allogenic blood transfusion should prompt a review of transfusion practices and justify the need to search for transfusion alternatives to decrease or avoid the use of allogenic blood. These strategies should include the correction of anemia using

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....

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

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

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...

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

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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.

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

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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

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

Experimental Study on Superfine Sand Concrete Mixed by Double Mixing Technology

OpenAIRE

yuqing zhao

2013-01-01

Traditional concept thought that medium sand and fine sand can be used to mix concrete, superfine sand can not used to mix concrete. This makes the source of superfine sand limited. With the shortage of medium sand and fine sand, it is imperative to exploit the resource of superfine sand. Superfine sand concrete is mixed by means of Double-doped Technology-ultra-fine fly ash and super plasticizer. Primary factor influencing superfine sand concrete strength is studied by orthogonal test, the o...

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.)

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

Sorption and release of organics by primary, anaerobic, and aerobic activated sludge mixed with raw municipal wastewater.

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Oskar Modin

Full Text Available New activated sludge processes that utilize sorption as a major mechanism for organics removal are being developed to maximize energy recovery from wastewater organics, or as enhanced primary treatment technologies. To model and optimize sorption-based activated sludge processes, further knowledge about sorption of organics onto sludge is needed. This study compared primary-, anaerobic-, and aerobic activated sludge as sorbents, determined sorption capacity and kinetics, and investigated some characteristics of the organics being sorbed. Batch sorption assays were carried out without aeration at a mixing velocity of 200 rpm. Only aerobic activated sludge showed net sorption of organics. Sorption of dissolved organics occurred by a near-instantaneous sorption event followed by a slower process that obeyed 1st order kinetics. Sorption of particulates also followed 1st order kinetics but there was no instantaneous sorption event; instead there was a release of particles upon mixing. The 5-min sorption capacity of activated sludge was 6.5±10.8 mg total organic carbon (TOC per g volatile suspend solids (VSS for particulate organics and 5.0±4.7 mgTOC/gVSS for dissolved organics. The observed instantaneous sorption appeared to be mainly due to organics larger than 20 kDa in size being sorbed, although molecules with a size of about 200 Da with strong UV absorbance at 215-230 nm were also rapidly removed.

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

Mixed-mode modelling mixing methodologies for organisational intervention

CERN Document Server

Clarke, Steve; Lehaney, Brian

2001-01-01

The 1980s and 1990s have seen a growing interest in research and practice in the use of methodologies within problem contexts characterised by a primary focus on technology, human issues, or power. During the last five to ten years, this has given rise to challenges regarding the ability of a single methodology to address all such contexts, and the consequent development of approaches which aim to mix methodologies within a single problem situation. This has been particularly so where the situation has called for a mix of technological (the so-called 'hard') and human­ centred (so-called 'soft') methods. The approach developed has been termed mixed-mode modelling. The area of mixed-mode modelling is relatively new, with the phrase being coined approximately four years ago by Brian Lehaney in a keynote paper published at the 1996 Annual Conference of the UK Operational Research Society. Mixed-mode modelling, as suggested above, is a new way of considering problem situations faced by organisations. Traditional...

A scoring system for appraising mixed methods research, and concomitantly appraising qualitative, quantitative and mixed methods primary studies in Mixed Studies Reviews.

Science.gov (United States)

Pluye, Pierre; Gagnon, Marie-Pierre; Griffiths, Frances; Johnson-Lafleur, Janique

2009-04-01

A new form of literature review has emerged, Mixed Studies Review (MSR). These reviews include qualitative, quantitative and mixed methods studies. In the present paper, we examine MSRs in health sciences, and provide guidance on processes that should be included and reported. However, there are no valid and usable criteria for concomitantly appraising the methodological quality of the qualitative, quantitative and mixed methods studies. To propose criteria for concomitantly appraising the methodological quality of qualitative, quantitative and mixed methods studies or study components. A three-step critical review was conducted. 2322 references were identified in MEDLINE, and their titles and abstracts were screened; 149 potentially relevant references were selected and the full-text papers were examined; 59 MSRs were retained and scrutinized using a deductive-inductive qualitative thematic data analysis. This revealed three types of MSR: convenience, reproducible, and systematic. Guided by a proposal, we conducted a qualitative thematic data analysis of the quality appraisal procedures used in the 17 systematic MSRs (SMSRs). Of 17 SMSRs, 12 showed clear quality appraisal procedures with explicit criteria but no SMSR used valid checklists to concomitantly appraise qualitative, quantitative and mixed methods studies. In two SMSRs, criteria were developed following a specific procedure. Checklists usually contained more criteria than needed. In four SMSRs, a reliability assessment was described or mentioned. While criteria for quality appraisal were usually based on descriptors that require specific methodological expertise (e.g., appropriateness), no SMSR described the fit between reviewers' expertise and appraised studies. Quality appraisal usually resulted in studies being ranked by methodological quality. A scoring system is proposed for concomitantly appraising the methodological quality of qualitative, quantitative and mixed methods studies for SMSRs. This

Role of Anatomic and Salivary Factors in Dental Calculus Formation in Primary and Mixed Dentition Stages.

Science.gov (United States)

Afshar, Hossein; Ghandehari, Mehdi; Khorsand, Afshin; Ansari, Ghassem; Nahvi, Azam; Baniameri, Zahra

2016-01-01

Clinical experience shows that formation of calculus is a very rare phenomenon in primary teeth, but it increases as the permanent teeth erupt. The purpose of this study was to assess the relationship between dental calculus, dental anatomy, and salivary factors in primary and mixed dentition stages. A cross-sectional study was carried out to determine the buccolingual dimensions of the most concave and the most convex surfaces of the lingual aspect of mandibular central incisor crowns in a sample group of 120 three- to five-old children and 120 eight- to 10-year old children. Saliva samples were collected from 20 in each group. Data were analyzed using t tests. Significant differences were found between the ratio of the buccolingual dimensions of the most convex to the most concave areas of the lingual surfaces in primary and permanent incisors (P=0.028). Saliva analysis revealed significant differences in total protein (P=0.002), sodium (P=0.037), bicarbonate (P=0.003), and ammonia (P=0.025) between the two age groups. Anatomic and salivary factors may be important reasons for the differences in calculus formation.

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

Pressure fluctuation characteristics of flow field of mixed flow nuclear primary pump

International Nuclear Information System (INIS)

Wang Chunlin; Yang Xiaoyong; Li Changjun; Jia Fei; Zhao Binjuan

2013-01-01

In order to research the pressure fluctuation characteristics of flow field of mixed flow nuclear primary pump, this study used the technique of ANSYS-Workbench and CFX fluid solid heat coupling to do numerical simulation analysis for model pump. According to the situation of pressure fluctuation of time domain and frequency domain, the main cause of pressure fluctuation was discussed. For different flow, the pressure fluctuations were compared. This study shows it is feasible that large eddy simulation method is used for the research of pressure fluctuation. The pressure fluctuation amplitudes of four sections are increasing from wheel hub to wheel rim. The pressure fluctuation of inlet and outlet of impeller depends on the rotational frequency of impeller. Along with the fluid flowing away from the impeller, the effect of the impeller on the fluid pressure fluctuation weakens gradually. Comparing the different results of three flow conditions, the pressure fluctuation in design condition flow is superior to the others. (authors)

Colour mixing based on daylight

International Nuclear Information System (INIS)

Meyn, Jan-Peter

2008-01-01

Colour science is based on the sensation of monochromatic light. In contrast to that, surface colours are caused by reflection of wide sections of the daylight spectrum. Non-spectral colours like magenta and purple appear homologous to colours with spectral hue, if the approach of mixing monochromatic light is abandoned. It is shown that a large region of the colour space can be covered by mixing three primary colours derived from lossless spectral decomposition of daylight. These primaries are specified by hue, saturation and luminosity. Duality of additive and subtractive mixing is formulated quantitatively. Experimental demonstrations of calculated results are suggested. This paper is intended for undergraduate optics courses, and advanced interdisciplinary seminars on arts and physics

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

Science.gov (United States)

Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

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

The challenges of meeting the blood transfusion requirements in Sub-Saharan Africa: the need for the development of alternatives to allogenic blood

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Erhabor Osaro

2011-02-01

Full Text Available Erhabor Osaro1, Adias Teddy Charles21Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Amassoma Bayelsa State, Nigeria; 2Department of Medical Laboratory Science, Rivers State University of Science and Technology, Port Harcourt, NigeriaAbstract: As a resource, allogenic blood has never been more in demand than it is today. Escalating elective surgery, shortages arising from a fall in supply, a lack of national blood transfusion services, policies, appropriate infrastructure, trained personnel, and financial resources to support the running of a voluntary nonremunerated donor transfusion service, and old and emerging threats of transfusion-transmitted infection, have all conspired to ensure that allogenic blood remains very much a vital but limited asset to healthcare delivery particularly in Sub-Saharan Africa. This is further aggravated by the predominance of family replacement and commercially remunerated blood donors, rather than regular benevolent, nonremunerated donors who give blood out of altruism. The demand for blood transfusion is high in Sub-Saharan Africa because of the high prevalence of anemia especially due to malaria and pregnancy-related complications. All stakeholders in blood transfusion have a significant challenge to apply the best available evidenced-based medical practices to the world-class management of this precious product in a bid to using blood more appropriately. Physicians in Sub-Saharan Africa must always keep in mind that the first and foremost strategy to avoid transfusion of allogenic blood is their thorough understanding of the pathophysiologic mechanisms involved in anemia and coagulopathy, and their thoughtful adherence to the evidenced-based good practices used in the developed world in a bid to potentially reduce the likelihood of allogenic blood transfusion in many patient groups. There is an urgent need to develop innovative ways to recruit and retain

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.)

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...

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.

Materials used for indirect pulp treatment in primary teeth: a mixed treatment comparisons meta-analysis

Directory of Open Access Journals (Sweden)

Pablo Silveira dos Santos

2017-12-01

Full Text Available Abstract: This study aimed to systematically review the literature to address the question regarding the influence of different materials in the clinical and radiographic success of indirect pulp treatment in primary teeth. A literature search was carried out for articles published prior to January 2017 in PubMed/MEDLINE, CENTRAL, Scopus, TRIP and ClinicalTrials databases; relevant articles included randomized clinical trials that compared materials used for indirect pulp treatment in primary teeth. Two reviewers independently selected the studies and extracted the data. The effects of each material on the outcome (clinical and radiographic failures were analyzed using a mixed treatment comparisons meta-analysis. The ranking of treatments according to their probability of being the best choice was also calculated. From 1,088 potentially eligible studies, 11 were selected for full-text analysis, and 4 were included in the meta-analysis. In all papers, calcium hydroxide liner was used as the control group versus an adhesive system, resin-modified glass ionomer cement or placebo. The follow-up period ranged from 24 to 48 months, with dropout rates of 0-25.7%. The material type did not significantly affect the risk of failure of the indirect pulp treatment. However, calcium hydroxide presented a higher probability of failure. In conclusion, there is no scientific evidence showing the superiority of any material used for indirect pulp treatment in primary teeth.

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.

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.

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.

Immune Reconstitution Kinetics following Intentionally Induced Mixed Chimerism by Nonmyeloablative Transplantation.

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Nayoun Kim

Full Text Available Establishing mixed chimerism is a promising approach for inducing donor-specific transplant tolerance. The establishment and maintenance of mixed chimerism may enable long-term engraftment of organ transplants while minimizing the use of immunosuppressants. Several protocols for inducing mixed chimerism have been reported; however, the exact mechanism underlying the development of immune tolerance remains to be elucidated. Therefore, understanding the kinetics of engraftment during early post-transplant period may provide insight into establishing long-term mixed chimerism and permanent transplant tolerance. In this study, we intentionally induced allogeneic mixed chimerism using a nonmyeloablative regimen by host natural killer (NK cell depletion and T cell-depleted bone marrow (BM grafts in a major histocompatibility complex (MHC-mismatched murine model and analyzed the kinetics of donor (C57BL/6 and recipient (BALB/c engraftment in the weeks following transplantation. Donor BM cells were well engrafted and stabilized without graft-versus-host disease (GVHD as early as one week post-bone marrow transplantation (BMT. Donor-derived thymic T cells were reconstituted four weeks after BMT; however, the emergence of newly developed T cells was more obvious at the periphery as early as two weeks after BMT. Also, the emergence and changes in ratio of recipient- and donor-derived NKT cells and antigen presenting cells (APCs including dendritic cells (DCs and B cells were noted after BMT. Here, we report a longitudinal analysis of the development of donor- and recipient-originated hematopoietic cells in various lymphatic tissues of intentionally induced mixed chimerism mouse model during early post-transplant period. Through the understanding of immune reconstitution at early time points after nonmyeloablative BMT, we suggest guidelines on intentionally inducing durable mixed chimerism.

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

Morphology, composition, and mixing state of primary particles from combustion sources - crop residue, wood, and solid waste.

Science.gov (United States)

Liu, Lei; Kong, Shaofei; Zhang, Yinxiao; Wang, Yuanyuan; Xu, Liang; Yan, Qin; Lingaswamy, A P; Shi, Zongbo; Lv, Senlin; Niu, Hongya; Shao, Longyi; Hu, Min; Zhang, Daizhou; Chen, Jianmin; Zhang, Xiaoye; Li, Weijun

2017-07-11

Morphology, composition, and mixing state of individual particles emitted from crop residue, wood, and solid waste combustion in a residential stove were analyzed using transmission electron microscopy (TEM). Our study showed that particles from crop residue and apple wood combustion were mainly organic matter (OM) in smoldering phase, whereas soot-OM internally mixed with K in flaming phase. Wild grass combustion in flaming phase released some Cl-rich-OM/soot particles and cardboard combustion released OM and S-rich particles. Interestingly, particles from hardwood (pear wood and bamboo) and softwood (cypress and pine wood) combustion were mainly soot and OM in the flaming phase, respectively. The combustion of foam boxes, rubber tires, and plastic bottles/bags in the flaming phase released large amounts of soot internally mixed with a small amount of OM, whereas the combustion of printed circuit boards and copper-core cables emitted large amounts of OM with Br-rich inclusions. In addition, the printed circuit board combustion released toxic metals containing Pb, Zn, Sn, and Sb. The results are important to document properties of primary particles from combustion sources, which can be used to trace the sources of ambient particles and to know their potential impacts in human health and radiative forcing in the air.

Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish primary health care

Directory of Open Access Journals (Sweden)

Fridh Gerd

2006-06-01

Full Text Available Abstract Background Individualbased measures for comorbidity are of increasing importance for planning and funding health care services. No measurement for individualbased healthcare costs exist in Sweden. The aim of this study was to validate the Johns Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4 or more prescription medicines used as a proxy for health care costs in an elderly population and to study if the prediction could be improved by adding variables from a population based study i.e. level of education, functional status indicators and health perception. Methods The Johns Hopkins ACG Case-Mix System was applied to primary health care diagnoses of 1402 participants (60–96 years in a cross-sectional community based study in Karlskrona, Sweden (the Swedish National study on Ageing and Care during a period of two years before they took part in the study. The predictive value of the Johns Hopkins ACG Case-Mix System was modeled against the regular use of 4 or more prescription medicines, also using age, sex, level of education, instrumental activity of daily living- and measures of health perception as covariates. Results In an exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to explain a large part of the variance for regular use of 4 or more prescription medicines. The sensitivity of the prediction was 31.9%, whereas the specificity was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By adding covariates to the model the sensitivity was increased to 46.3%, with a specificity of 90.1%. This increased the number of correctly classified by 5.6% and the area under the curve by 11.1%. Conclusion The Johns Hopkins ACG Case-Mix System is an important factor in measuring comorbidity, however it does not reflect an individual's capability to function despite a disease burden, which has importance for prediction of comorbidity. In this study we have shown that

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.)

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)

Choice of primary health care source in an urbanized low-income community in Singapore: a mixed-methods study.

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Wee, Liang En; Lim, Li Yan; Shen, Tong; Lee, Elis Yuexian; Chia, Yet Hong; Tan, Andrew Yen Siong; Koh, Gerald Choon-Huat

2014-02-01

Cost and misperceptions may discourage lower income Singaporeans from utilizing primary care. We investigated sources of primary care in a low-income Singaporean community in a mixed-methods study. Residents of a low-income public rental flat neighbourhood were asked for sociodemographic details and preferred source of primary care relative to their higher income neighbours. In the qualitative component, interviewers elicited, from patients and health care providers, barriers/enablers to seeking care from Western-trained doctors. Interviewees were selected via purposive sampling. Transcripts were analyzed thematically, and iterative analysis was carried out using established qualitative method. Participation was 89.8% (359/400). Only 11.1% (40/359) preferred to approach Western-trained doctors, 29.5% (106/359) preferred alternative medicine, 6.7% (24/359) approached family/friends and 52.6% (189/359) preferred self-reliance. Comparing against higher income neighbours, rental flat residents were more likely to turn to alternative medicine and family members but less likely to turn to Western-trained doctors (P Self-reliance was perceived as acceptable for 'small' illnesses but not for 'big' ones, communal spirit was cited as a reason for consulting family/friends and social distance from primary care practitioners was highlighted as a reason for not consulting Western-trained doctors. Western-trained physicians are not the first choice of lower income Singaporeans for seeking primary care. Knowledge, primary care characteristics and costs were identified as potential barriers/enablers.

Preliminary analysis in support to the experimental activities on the mixing process in the pressurizer of a small modular reactor integrated primary system

Energy Technology Data Exchange (ETDEWEB)

Nascimento, Samira R.V.; Lira, Carlos A.B.O.; Bezerra, Jair L.; Silva, Mario A.B.; Silva, Willdauany C.F., E-mail: samiraruana@gmail.com [Universidade Federal de Pernambuco (DEN/UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear; Lapa, Celso M.F., E-mail: lapa@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Lima, Fernando R.A., E-mail: falima@crcn.gov.br [Centro Regional de Ciencias Nucleares (CRCN/CNEN-NE), Recife, PE (Brazil); Otero, Maria E.M.; Hernandez, Carlos R.G., E-mail: mmontesi@instec.cu [Department of Nuclear Engineering, InSTEC/CUBA, Higher Institute of Technology and Applied Science, La Habana (Cuba)

2015-07-01

Nowadays, there is a renewed interest in the development of advanced/innovative small and medium sized modular reactors (SMRs). The SMRs are variants of the Generation IV systems and usually have attractive characteristics of simplicity, enhanced safety and require limited financial resources. The concept of the integrated primary system reactor (IPSR) is characterized by the inclusion of the entire primary system within a single pressure vessel, including the steam generator and pressurizer. The pressurizer is located within the reactor vessel top, this configuration involves changes on the techniques and is necessary investigate the boron mixing. The present work represents a contribution to the design of an experimental facility planned to provide data relevant for the mixing phenomena in the pressurizer of a compact modular reactor. In particular, in order to evaluate the boron concentration in the surge orifices to simulate the in-surge and out-surge in a facility, scaled 1:200, respect to the ¼ of the pressurizer. The facility behavior studied from one inlet and one outlet of the test section with represent one in-surge e one out-surge the pressurizer of a small modular reactor integrated primary system. (author)

Assessing mixed anxiety-depressive disorder. A national primary care survey.

Science.gov (United States)

Balestrieri, Matteo; Isola, Miriam; Quartaroli, Mauro; Roncolato, Maurizio; Bellantuono, Cesario

2010-04-30

Prevalence and risk factors associated with mixed anxiety-depressive disorder (MAD) have yet to be established. Using MINI 5.0.1 and HADS, a two-week survey involving 21,644 primary care patients was carried out. We found 1.8% of subjects with MAD and 20% of subjects with a co-morbid anxiety and depression (CAD) disorder. MAD patients without a past history of anxiety/affective episodes were defined as "pure MAD" (pMAD: 0.9% of the sample). While MAD patients showed a number of differences vs. the other groups of patients in the socio-demographic statistics, pMAD patients were not different, apart from a higher proportion of males vs. CAD patients. Nearly in all the comparisons, MAD and pMAD patients showed lower association with life events and with a familial predisposition than the other patients. On HADS assessment, MAD showed a higher risk of anxiety and depressive symptoms than anxiety diagnoses, a lower risk of depressive symptoms than depressive diagnoses and a lower risk of both anxiety and depressive symptoms than CAD. Since more than a half of MAD patients were classified as pMAD, the hypothesis that MAD should be viewed as a partial remission of a major depression is not entirely confirmed in our study. Copyright (c) 2008 Elsevier Ltd. All rights reserved.

Successful repigmentation of vitiligo after allogeneic bone marrow transplantation for Hodgkin′s lymphoma by autologous noncultured melanocyte-keratinocyte transplantation

Directory of Open Access Journals (Sweden)

Huijuan Tang

2015-01-01

Full Text Available The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin′s lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

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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

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)

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.

The primary results for the mixed carbon material used for high flux steady-state tokamak operation in China

International Nuclear Information System (INIS)

Guo, Q.G.; Li, J.G.; Zhai, G.T.; Liu, L.; Song, J.R.; Zhang, L.F.; He, Y.X.; Chen, J.L.

2001-01-01

Several types of carbon mixed materials have been developed in China to be used for high flux steady-state tokamak operation. Performance evaluation of these materials is necessary to determine their applicability as PFCs for high flux steady state. This paper describes the primary results of carbon mixed materials and the effects of dopants on properties are primarily discussed. Test results reveal that bulk boronized graphite has excellent physical and mechanical properties while their thermal conductivity is no more than 73 W/m K due to the formation of a uniform boron-carbon solid solution. In case of multi-element doped graphite, titanium dopant or a decreased boron content is favorable to enhance thermal conductivity. A kind of doped graphite has been developed with thermal conductivity as high as 278 W/m K by optimizing the compositions. Correlations among compositions, microstructure and properties of such doped graphite are discussed

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.

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

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.

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.

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.

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

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.

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

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

Full Text Available Xenogeneic chondrocytes and allogeneic mesenchymal stem cells (MSC are considered a potential source of cells for articular cartilage repair. We here assessed the immune response triggered by xenogeneic chondrocytes when injected intraarticularly, as well as the immunoregulatory effect of allogeneic bone marrow-derived MSC after systemic administration. To this end, a discordant xenotransplantation model was established by injecting three million porcine articular chondrocytes (PAC into the femorotibial joint of Lewis rats and monitoring the immune response. First, the fate of MSC injected using various routes was monitored in an in vivo imaging system. The biodistribution revealed a dependency on the injection route with MSC injected intravenously (i.v. succumbing early after 24 h and MSC injected intraperitoneally (i.p. lasting locally for at least 5 days. Importantly, no migration of MSC to the joint was detected in rats previously injected with PAC. MSC were then administered either i.v. 1 week before PAC injection or i.p. 3 weeks after to assess their immunomodulatory function on humoral and adaptive immune parameters. Anti-PAC IgM and IgG responses were detected in all PAC-injected rats with a peak at week 2 postinjection and reactivity remaining above baseline levels by week 18. IgG2a and IgG2b were the predominant and long-lasting IgG subtypes. By contrast, no anti-MSC antibody response was detected in the cohort injected with MSC only, but infusion of MSC before PAC injection temporarily augmented the anti-PAC antibody response. Consistent with a cellular immune response to PAC in PAC-injected rats, cytokine/chemokine profiling in serum by antibody array revealed a distinct pattern relative to controls characterized by elevation of multiple markers at week 2, as well as increases in proliferation in draining lymph nodes. Notably, systemic administration of allogeneic MSC under the described conditions did not diminish the immune

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.)

Slow conduction in mixed cultured strands of primary ventricular cells and stem cell-derived cardiomyocytes

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Jan Pavel Kucera

2015-09-01

Full Text Available Modern concepts for the treatment of myocardial diseases focus on novel cell therapeutic strategies involving stem cell-derived cardiomyocytes (SCMs. However, functional integration of SCMs requires similar electrophysiological properties as primary cardiomyocytes (PCMs and the ability to establish intercellular connections with host myocytes in order to contribute to the electrical and mechanical activity of the heart. The aim of this project was to investigate the properties of cardiac conduction in a co-culture approach using SCMs and PCMs in cultured cell strands. Murine embryonic SCMs were pooled with fetal ventricular cells and seeded in predefined proportions on microelectrode arrays to form patterned strands of mixed cells. Conduction velocity (CV was measured during steady state pacing. SCM excitability was estimated from action potentials measured in single cells using the patch clamp technique. Experiments were complemented with computer simulations of conduction using a detailed model of cellular architecture in mixed cell strands.CV was significantly lower in strands composed purely of SCMs (5.5±1.5 cm/s, n=11 as compared to PCMs (34.9±2.9 cm/s, n=21 at similar refractoriness (100% SCMs: 122±25 ms, n=9; 100% PCMs: 139±67 ms, n=14. In mixed strands combining both cell types, CV was higher than in pure SCMs strands, but always lower than in 100% PCM strands. Computer simulations demonstrated that both intercellular coupling and electrical excitability limit CV.These data provide evidence that in cultures of murine ventricular cardiomyocytes, SCMs cannot restore CV to control levels resulting in slow conduction, which may lead to reentry circuits and arrhythmias.

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...

Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

Science.gov (United States)

Cruz, Conrad Russell Y; Micklethwaite, Kenneth P; Savoldo, Barbara; Ramos, Carlos A; Lam, Sharon; Ku, Stephanie; Diouf, Oumar; Liu, Enli; Barrett, A John; Ito, Sawa; Shpall, Elizabeth J; Krance, Robert A; Kamble, Rammurti T; Carrum, George; Hosing, Chitra M; Gee, Adrian P; Mei, Zhuyong; Grilley, Bambi J; Heslop, Helen E; Rooney, Cliona M; Brenner, Malcolm K; Bollard, Catherine M; Dotti, Gianpietro

2013-10-24

Autologous T cells expressing a CD19-specific chimeric antigen receptor (CD19.CAR) are active against B-cell malignancies, but it is unknown whether allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic stem cell transplantation (HSCT), infused donor-derived virus-specific T cells (VSTs) expand in vivo, persist long term, and display antiviral activity without inducing graft-vs-host disease; therefore, we determined whether donor VSTs, engineered to express CD19.CAR, retained the characteristics of nonmanipulated allogeneic VSTs while gaining antitumor activity. We treated 8 patients with allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in blood and up to 9 weeks at disease sites. Objective antitumor activity was evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR-VST persistence, whereas 2 patients who received cells while in remission remain disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity and, because their number may be increased in the presence of viral stimuli, earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of viral infection is higher) or planned vaccination with viral antigens may enhance disease control.

Extragenital malignant mixed Mullerian tumor in the incisional hernia - primary carcinosarcoma in the abdominal wall: Case report

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Žuvela Marinko

2015-01-01

Full Text Available Introduction. This report presents a primary Mullerian carcinosarcoma localized in the incisional hernia i.e. anterior abdominal wall. There is no data in the literature about this localization of extragenital Mullerian carcinosarcoma. Case Outline. The patient had previous medical history of right-sided ovarian cystadenocarcinoma managed by hysterectomy, bilateral ovariectomy and chemotherapy. An incisional hernia occurred 1 year after the operation and Mullerian carcinosarcoma at the right border of the incisional hernia 16 years later. There was no tumor spreading into the abdominal cavity and pelvis. Full thickness of the abdominal wall resection and coexisting incisional hernia resulted in a large 25x20 cm abdominal wall defect managed by the modified components separation technique and implanting meshes. Conclusion. Major abdominal wall resection and abdominal wall reconstruction using the modified components separation technique reinforced with meshes could be one of possible solutions in the surgical treatment of primary malignant mixed Mullerian tumor localized in the abdominal wall. [Projekat Ministarstva nauke Republike Srbije, br. 41030

Mixed dyslipidemias in primary care patients in France

Science.gov (United States)

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

Objective To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. Methods This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Main outcome measures Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. Results At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. Conclusions At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients. PMID:22566746

Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

International Nuclear Information System (INIS)

Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

1988-01-01

When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

Case-mix tool, costs and effectiveness in improving primary care mental health and substance abuse services.

Science.gov (United States)

Riihimäki, Kirsi; Heiska-Johansson, Ainomaija; Ketola, Eeva

2018-02-01

Despite its importance in improving care and developing services, high-quality data evaluating cost-effectiveness and services in different case-mix populations is scarce in primary care. The objective was to investigate the service use of those mental health and substance abuse patients, who use lots of services. Primary health care diagnosis-related groups (pDRG) is a tool to evaluate service provider system and improve efficiency, productivity and quality. We viewed all pDRG results available from the year 2015 concerning municipal mental health and substance abuse services. In primary care mental health and substance abuse services, the most common ICD-10-codes were depression and substance abuse. One-fifth of patients produced 57% of costs. Their medium of appointments was 16 per year versus 6 per year of all patients. Only 54% of their diagnoses were recorded in the electronic health records versus 75% of all patients. They made 5.7 different pDRG episodes, including 1.8 episodes of depression, per patient. The average episode cost for this patient group was 301€. pDRG makes health care production transparent also in mental health and substance abuse services. It is easy to identify patients, who use a lot of services and thus induce the majority of costs, and focus on their needs in managing and developing services.

HLA-E-Restricted Cross-Recognition of Allogeneic Endothelial Cells by CMV-Associated CD8 T Cells: A Potential Risk Factor following Transplantation

Science.gov (United States)

Allard, Mathilde; Tonnerre, Pierre; Nedellec, Steven; Oger, Romain; Morice, Alexis; Guilloux, Yannick; Houssaint, Elisabeth; Charreau, Béatrice; Gervois, Nadine

2012-01-01

Although association between CMV infection and allograft rejection is well admitted, the precise mechanisms involved remain uncertain. Here, we report the characterization of an alloreactive HLA-E-restricted CD8 T cell population that was detected in the PBL of a kidney transplant patient after its CMV conversion. This monoclonal CD8 T cell population represents a sizable fraction in the blood (3% of PBL) and is characterized by an effector-memory phenotype and the expression of multiple NK receptors. Interestingly, these unconventional T cells display HLA-E-dependent reactivity against peptides derived from the leader sequences of both various HCMV-UL40 and allogeneic classical HLA-I molecules. Consequently, while HLA-E-restricted CD8 T cells have potential to contribute to the control of CMV infection in vivo, they may also directly mediate graft rejection through recognition of peptides derived from allogeneic HLA-I molecules on graft cells. Therefore, as HLA-E expression in nonlymphoid organs is mainly restricted to endothelial cells, we investigated the reactivity of this HLA-E-restricted T cell population towards allogeneic endothelial cells. We clearly demonstrated that CMV-associated HLA-E-restricted T cells efficiently recognized and killed allogeneic endothelial cells in vitro. Moreover, our data indicate that this alloreactivity is tightly regulated by NK receptors, especially by inhibitory KIR2DL2 that strongly prevents TCR-induced activation through recognition of HLA-C molecules. Hence, a better evaluation of the role of CMV-associated HLA-E-restricted T cells in transplantation and of the impact of HLA-genotype, especially HLA-C, on their alloreactivity may determine whether they indeed represent a risk factor following organ transplantation. PMID:23226431

Critical Appraisal of Mixed Methods Studies

Science.gov (United States)

Heyvaert, Mieke; Hannes, Karin; Maes, Bea; Onghena, Patrick

2013-01-01

In several subdomains of the social, behavioral, health, and human sciences, research questions are increasingly answered through mixed methods studies, combining qualitative and quantitative evidence and research elements. Accordingly, the importance of including those primary mixed methods research articles in systematic reviews grows. It is…

Mixed Movements

DEFF Research Database (Denmark)

Brabrand, Helle

2010-01-01

levels than those related to building, and this exploration is a special challenge and competence implicit artistic development work. The project Mixed Movements generates drawing-material, not primary as representation, but as a performance-based media, making the body being-in-the-media felt and appear...... as possible operational moves....

Investigation of epstein-barr virus and parvovirus b19 DNA in allogeneic stem cell transplant patients.

Science.gov (United States)

Atalay, Altay; Gökahmetoğlu, Selma; Durmaz, Süleyman; Kandemir, Idris; Sağlam, Derya; Kaynar, Leylagül; Eser, Bülent; Cetin, Mustafa; Kılıç, Hüseyin

2014-06-01

We aimed to investigate posttransplant Epstein-Barr virus (EBV) and parvovirus B19 DNA in allogeneic stem cell transplant patients between 2009 and 2010. Forty-five adult patients in whom allogeneic stem cell transplantation was performed between April 2009 and November 2010 in the Erciyes University Faculty of Medicine, Department of Internal Medicine, Division of Hematology and Oncology, were included in the study. EBV and parvovirus B19 DNA positivity was investigated by using real-time polymerase chain reaction technique in 135 plasma samples obtained after transplantation at between 1 and 6 months. Pretransplant serological markers of EBV and parvovirus B19 were provided from patient files. In 32 (71.1%) of the patients, EBV antibodies in the pretransplantation period were as follows: anti-EBNA-1 IgG (+), VCA IgM (-), and VCA IgG (+). In 2 patients (4.45%), these antibodies were as follows: anti-EBNA-1 IgG (+), VCA IgM (-), and VCA IgG (-). In 1 patient (2.2%), they were as follows: anti-EBNA-1 IgG (-), VCA IgM (-), and VCA IgG (+). EBV serological markers were negative in 2 (2.2%) out of 45 patients before transplantation. There was low DNA positivity (parvovirus B19 IgM was negative and IgG was positive, parvovirus B19 IgM was positive and IgG was negative in 1 (2.3%) patient. Parvovirus B19 DNA was not identified in any of the samples obtained from these 45 patients. In this study, EBV and parvovirus B19 DNA were investigated in allogeneic stem cell transplant patients. None of the patients developed PTLD and parvovirus B19 DNA positivity was not detected. However, this issue needs to be further evaluated in prospective, multicenter studies with larger series of patients.

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

* Comparison of Autologous, Allogeneic, and Cell-Free Scaffold Approaches for Engineered Tendon Repair in a Rabbit Model-A Pilot Study.

Science.gov (United States)

Wang, Wenbo; Deng, Dan; Wang, Bin; Zhou, Guangdong; Zhang, WenJie; Cao, Yilin; Zhang, Peihua; Liu, Wei

2017-08-01

Tendons are subjected to high strength dynamic mechanical forces in vivo. Mechanical strength is an essential requirement for tendon scaffold materials. A composite scaffold was used in this study to provide mechanical strength, which was composed of an inter part of nonwoven polyglycolic acid (PGA) fibers and an outer part of the net knitted with PGA and polylactic acid (PLA) fibers in a ratio of 4:2. This study compared three different approaches for in vivo tendon engineering, that is, cell-free scaffold and allogeneic and autologous cell seeded scaffolds, using a rabbit Achilles tendon repair model. Dermal fibroblasts were, respectively, isolated from the dermis of regular rabbits or green fluorescence protein transgenic rabbits as the autologous and the allogeneic cell sources, respectively. The cell scaffolds and cell-free scaffolds were implanted to bridge a partial segmental defect of rabbit Achilles tendon. The engineered tendons were harvested at 7 and 13 months postsurgery for various examinations. The results showed that all three groups could achieve in vivo tendon regeneration similarly with slightly better tissue formation in autologous group than in other two groups, including better scaffold degradation and relatively thicker collagen fibrils. There were no statistically significant differences in mechanical parameters among three groups. This work demonstrated that allogeneic fibroblasts and scaffold alone are likely to be used for tendon tissue engineering.

Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

International Nuclear Information System (INIS)

Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

1977-01-01

The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

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.

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

Benign mixed tumor of the lacrimal sac

Directory of Open Access Journals (Sweden)

Jong-Suk Lee

2015-01-01

Full Text Available Neoplasms of the lacrimal drainage system are uncommon, but potentially life-threatening and are often difficult to diagnose. Among primary lacrimal sac tumors, benign mixed tumors are extremely rare. Histologically, benign mixed tumors have been classified as a type of benign epithelial tumor. Here we report a case of benign mixed tumor of the lacrimal sac.

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.

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.

Psychological impact of family history risk assessment in primary care: a mixed methods study.

Science.gov (United States)

Birt, Linda; Emery, Jon D; Prevost, A Toby; Sutton, Stephen; Walter, Fiona M

2014-08-01

Routine family history risk assessment for chronic diseases could enable primary care practitioners to efficiently identify at-risk patients and promote preventive management strategies. To investigate patients' understanding and responses to family history risk assessment in primary care. A mixed methods study set in 10 Eastern England general practices. Participants in a family history questionnaire validation study were triaged into population or increased risk for four chronic diseases (type 2 diabetes, cardiovascular disease, breast cancer, colorectal cancer). Questionnaires completed immediately prior to the family history consultation (baseline) and 4 weeks later (follow-up) assessed the psychological impact, including State-Trait Anxiety Inventory scores. Semi-structured interviews explored the meaning participants gave to their personal familial disease risk. Four hundred and fifty-three participants completed both baseline and follow-up questionnaires and 30 were interviewed. At follow-up, there was no increase in anxiety among either group, or differences between the groups [difference in mean change 0.02, 95% confidence interval -2.04, 2.08, P = 0.98]. There were no significant changes over time in self-rated health in either group. At follow-up, participants at increased risk (n = 153) were more likely to have recent changes to behaviour and they had stronger intentions to make changes to diet (P = 0.001), physical activity (P = 0.006) and to seek further information in the future than those at population risk (n = 300; P assessment for familial risk of chronic diseases may be undertaken in primary care without causing anxiety or reducing self-rated health. Patient responses to family history risk assessment may inform promotion of preventive management strategies. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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....

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...

Primary productivity

Digital Repository Service at National Institute of Oceanography (India)

Verlecar, X.N.; Parulekar, A.H.

Photosynthetic production in the oceans in relation to light, nutrients and mixing processes is discussed. Primary productivity in the estuarine region is reported to be high in comparison to coastal and oceanic waters. Upwelling phenomenon...

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).

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

Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

International Nuclear Information System (INIS)

Yu, J.C.; Webster, M.; Fox, I.J.

1990-01-01

The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice

Genetic DNA profile in urine and hair follicles from patients who have undergone allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Santurtún, Ana; Riancho, José A; Santurtún, Maite; Richard, Carlos; Colorado, M Mercedes; García Unzueta, Mayte; Zarrabeitia, María T

2017-09-01

Biological samples from patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) constitute a challenge for individual identification. In this study we analyzed the genetic profiles (by the amplification of 15 autosomic STRs) of HSCT patients found in different types of samples (blood, hair and urine) that may be the source of DNA in civil or criminal forensic cases. Our results show that while in hair follicles the donor component was not detected in any patient, thus being a reliable source of biological material for forensic identification, mixed chimerism was detected in urine samples from all patient, and no correlation was found between the time elapsed from the transplant and the percentage of chimerism. These results certainly have practical implications if the urine is being considered as a source of DNA for identification purposes in HSTC patients. Moreover, taking into consideration that chimerism was found not only in patients with leukocyturia (given the hematopoietic origin of leukocytes, this was expected), but also in those without observable leukocytes in the sediment, we conclude that an alternative source or sources of donor DNA must be implicated. Copyright © 2017 The Chartered Society of Forensic Sciences. Published by Elsevier B.V. All rights reserved.

Are chiropractors in the uk primary healthcare or primary contact practitioners?: a mixed methods study

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Jones-Harris Amanda R

2010-10-01

Full Text Available Abstract Background One of the debates regarding the role of chiropractors is whether or not they should be considered as primary healthcare practitioners. Primary care is often used to describe chiropractic but without any definition of what is meant by the term. Primary healthcare itself has many definitions and this adds to the problem. Existing research literature, based mostly in the USA, suggests that the use of the title "primary healthcare professional" by chiropractors is central to the identity of the profession. It has also been suggested that the concept of primary care is misused by chiropractors because they have not examined the concept in detail and thus do not understand it. For the sake of quality of patient care and for the legitimacy of the profession, chiropractors in the UK need to agree on their healthcare role. This study aimed to examine the opinions of chiropractors towards the use of the term primary healthcare when applied to chiropractic practice within the UK. Methods A sequential study of exploratory design was used; this model is characterised by an initial phase of qualitative data collection and analysis that precedes and informs the quantitative phase of data collection and analysis. In this study, interviews with members of chiropractic teaching faculty were used to inform the development of a questionnaire used to survey the opinions of chiropractors in the UK. Results There was a general consensus of opinion that chiropractors are primary contact practitioners, who work in a primary healthcare setting and that to be able to fulfil this healthcare role, chiropractors must be able to diagnose patients and refer when required. Participants did not feel that chiropractors are able to treat all of the most common medical conditions that present in a primary healthcare setting. Conclusions The findings of this study suggest that chiropractors in the UK view their role as one of a primary contact healthcare

Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission

International Nuclear Information System (INIS)

Inoue, T.; Ikeda, H.; Yamazaki, H.; Tang, J.T.; Song, C.; Teshima, T.; Murayama, S.; Ohtani, M.; Shibata, H.; Masaoka, T.

1993-01-01

The role of total body irradiation (TBI) for allogeneic bone marrow transplantation (BMT) for acute leukemia in first complete remission was reevaluated in this study. From Japanese BMT Registry, data of 123 acute leukemia patients in first complete remission who underwent allogeneic bone marrow transplantation in 22 hospitals between 1988 and 1990 were available for the present comparative study of preparation regimens with or without total body irradiation. Two-year survivals were 77% and 51% in the TBI containing regimen group and in the non-TBI regimen group, respectively (p=0.0010). Corresponding two-year relapse rates were 16% and 37%, respectively (p=0.0197). Corresponding probabilities of developing interstitial pneumonitis were 21% and 24%, respectively (p=0.8127). The analysis of causes of death indicated that non-TBI regimen increased the incidence of septicemia and lethal organ failures, such as liver, heart, lung and other multiple sites. It was emphasized that an additional role of total body irradiation was to disperse the treatment-related toxicity in allogeneic bone marrow transplantation for acute leukemia. (orig.) [de

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.

Experiences with primary healthcare in Fuzhou, urban China, in the context of health sector reform: a mixed methods study.

Science.gov (United States)

McCollum, Rosalind; Chen, Lieping; ChenXiang, Tang; Liu, Xiaoyun; Starfield, Barbara; Jinhuan, Zheng; Tolhurst, Rachel

2014-01-01

China has recently placed increased emphasis on the provision of primary healthcare services through health sector reform, in response to inequitably distributed health services. With increasing funding for community level facilities, now is an opportune time to assess the quality of primary care delivery and identify areas in need of further improvement. A mixed methodology approach was adopted for this study. Quantitative data were collected using the Primary Care Assessment Tool-Chinese version (C-PCAT), a questionnaire previously adapted for use in China to assess the quality of care at each health facility, based on clients' experiences. In addition, qualitative data were gathered through eight semi-structured interviews exploring perceptions of primary care with health directors and a policy maker to place this issue in the context of health sector reform. The study found that patients attending community health and sub-community health centres are more likely to report better experiences with primary care attributes than patients attending hospital facilities. Generally low scores for community orientation, family centredness and coordination in all types of health facility indicate an urgent need for improvement in these areas. Healthcare directors and policy makers perceived the need for greater coordination between levels of health providers, better financial reimbursement, more formal government contracts and recognition/higher status for staff at the community level and more appropriate undergraduate and postgraduate training. Copyright © 2013 John Wiley & Sons, Ltd.

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...

Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

International Nuclear Information System (INIS)

Sharabi, Y.; Sachs, D.H.

1989-01-01

The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia

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

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.

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.

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

Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia : a population-matched analysis

NARCIS (Netherlands)

Dreger, P; Brand, R; Milligan, D; Corradini, P; Finke, J; Deliliers, GL; Martino, R; Russell, N; van Biezen, A; Michallet, M; Niederwieser, D

To elucidate whether reduced-intensity conditioning (RIC) decreases treatment-related mortality (TRM) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL), we retrospectively compared 73 RIC cases from a recent EBMT survey with 82 patients from the EBMT

Skill mix change between general practitioners, nurse practitioners, physician assistants and nurses in primary healthcare for older people: a qualitative study.

Science.gov (United States)

Lovink, Marleen H; van Vught, Anneke J A H; Persoon, Anke; Schoonhoven, Lisette; Koopmans, Raymond T C M; Laurant, Miranda G H

2018-05-02

More and more older adults desire to and are enabled to grow old in their own home, regardless of their physical and mental capabilities. This change, together with the growing number of older adults, increases the demand for general practitioners (GPs). However, care for older people lacks prestige among medical students and few medical students are interested in a career in care for older people. Innovative solutions are needed to reduce the demand for GPs, to guarantee quality of healthcare and to contain costs. A solution might be found in skill mix change by introducing nurse practitioners (NPs), physician assistants (PAs) or registered nurses (RNs). The aim of this study was to describe how skill mix change is organised in daily practice, what influences it and what the effects are of introducing NPs, PAs or RNs into primary healthcare for older people. In total, 34 care providers working in primary healthcare in the Netherlands were interviewed: GPs (n = 9), NPs (n = 10), PAs (n = 5) and RNs (n = 10). Five focus groups and 14 individual interviews were conducted. Analysis consisted of open coding, creating categories and abstraction. In most cases, healthcare for older people was only a small part of the tasks of NPs, PAs and RNs; they did not solely focus on older people. The tasks they performed and their responsibilities in healthcare for older people differed between, as well as within, professions. Although the interviewees debated the usefulness of proactive structural screening on frailty in the older population, when implemented, it was also unclear who should perform the geriatric assessment. Interviewees considered NPs, PAs and RNs an added value, and it was stated that the role of the GP changed with the introduction of NPs, PAs or RNs. The roles and responsibilities of NPs, PAs and RNs for the care of older people living at home are still not established. Nonetheless, these examples show the potential of these professionals. The

Response to intravenous allogeneic equine cord-blood-derived mesenchymal stromal cells administered from chilled or frozen state in serum and protein free media

Directory of Open Access Journals (Sweden)

Lynn Brandon Williams

2016-07-01

Full Text Available Equine Mesenchymal stromal cells (MSC are commonly transported, chilled or frozen, to veterinary clinics. These MSC must remain viable and minimally affected by culture, transport, or injection processes. The safety of two carrier solutions developed for optimal viability and excipient use were evaluated in ponies, with and without allogeneic cord blood-derived (CB MSC. We hypothesized that neither the carrier solutions nor CB-MSC would elicit measurable changes in clinical, hematological, or biochemical parameters. In 9 ponies (study 1 a bolus of HypoThermosol® FRS (HTS-FRS, CryoStor® CS10 (CS10 or saline was injected IV (n=3/treatment. Study 2, following a one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in HTS-FRS following 24h simulated chilled transport. Study 3, following another one week washout period 5x107 pooled allogeneic CB-MSC were administered IV in CS10 immediately after thawing. Nine ponies received CB-MSCs in study 2 and 3 and three ponies received the cell carrier media without cells. CB-MSCs were pooled in equal numbers from five unrelated donors. In all studies ponies were monitored with physical examination, and blood collection for 7 days following injection. CD4 and CD8 lymphocyte populations were also evaluated in each blood sample.In all three studies, physical exam, complete blood cell count, serum biochemistry, and coagulation panel did not deviate from established normal ranges. Proportions of CD4+ and CD8+ lymphocytes increased at 168h post injection in CB-MSC treatment groups regardless of the carrier solution. Decreases in CD4+/CD8+ double positive populations were observed at 24 h and 72 h in CB-MSC treated animals. There was no difference in viability between CB-MSC suspended in HTS-FRS or CS10.HTS-FRS and CS10 used for low volume excipient injection of MSC suspensions was not associated with short-term adverse reactions. HTS-FRS and CS10 both adequately maintain CB-MSC viability

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.

Allogeneic blood transfusion and prognosis following total hip replacement: a population-based follow up study

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Overgaard Soren

2009-12-01

Full Text Available Abstract 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 with matched non-transfused patients: the adjusted OR was 2.2 (95% confidence interval (CI: 1.2-3.8. Blood transfusion was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8, whereas the associations with cardiovascular or cerebrovascular events (OR 1.4; CI: 0.9-2.2 and venous thromboembolism (OR 1.2; CI: 0.7-2.1 did not reach statistical significance. The adjusted OR of reoperation due to infection was 0.6 (CI: 0.1-2.9. Conclusions Red blood cell transfusion was associated with an adverse prognosis following primary THR, in particular with increased odds of death and pneumonia. Although the odds estimates may partly reflect unmeasured bias due to blood loss, they indicate the need for careful assessment of the risk versus benefit of transfusion even in relation to routine THR procedures.

Age- and dose-related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors

International Nuclear Information System (INIS)

Akiyama, Mitoshi; Zhou, Ou-Liang; Kusunoki, Yoichiro; Kyoizumi, Seishi; Kohno, Nobuoki; Akiba, Suminori; Delongchamp, R.R.

1988-07-01

The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic bomb survivors. The study revealed a significant decrease in MLC with increasing dose of previous radiation exposure. This decline was remarkable in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T-cells for the immune system. Thus it may be that, in the advanced age ATB group, the thymus function has started to involute allowing less recovery of T-cell function compared to young survivors who have adequate processing T-cell activity. (author)

Towards effective and safe immunotherapy after allogeneic stem cell transplantation: identification of hematopoietic-specific minor histocompatibility antigen UTA2-1

NARCIS (Netherlands)

Oostvogels, R.; Minnema, M. C.; van Elk, M.; Spaapen, R. M.; te Raa, G. D.; Giovannone, B.; Buijs, A.; van Baarle, D.; Kater, A. P.; Griffioen, M.; Spierings, E.; Lokhorst, H. M.; Mutis, T.

2013-01-01

Donor T cells directed at hematopoietic system-specific minor histoconnpatibility antigens (mHags) are considered important cellular tools to induce therapeutic graft-versus-tumor (GvT) effects with low risk of graft-versus-host disease after allogeneic stem cell transplantation. To enable the

Development of donor-derived thymic lymphomas after allogeneic bone marrow transplantation in AKR/J mice

International Nuclear Information System (INIS)

Yasumizu, R.; Hiai, H.; Sugiura, K.

1988-01-01

The transplantation of bone marrow cells from BALB/c (but not C57BL/6 and C3H/HeN) mice was observed to lead to the development of thymic lymphomas (leukemias) in AKR/J mice. Two leukemic cell lines, CAK1.3 and CAK4.4, were established from the primary culture of two thymic lymphoma, and surface phenotypes of these cell lines found to be H-2d and Thy-1.2+, indicating that these lymphoma cells are derived from BALB/c donor bone marrow cells. Further analyses of surface markers revealed that CAK1.3 is L3T4+ Lyt2+ IL2R-, whereas CAK4.4 is L3T4- Lyt2- IL2R+. Both CAK1.3 and CAK4.4 were transplantable into BALB/c but not AKR/J mice, further indicating that these cells are of BALB/c bone marrow donor origin. The cells were found to produce XC+-ecotropic viruses, but xenotropic and mink cell focus-forming viruses were undetectable. Inasmuch as thymic lymphomas are derived from bone marrow cells of leukemia-resistant BALB/c strain of mice under the allogeneic environment of leukemia-prone AKR/J mice, this animal model may serve as a useful tool not only for the analysis of leukemic relapse after bone marrow transplantation but also for elucidation of the mechanism of leukemogenesis

Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients.

Science.gov (United States)

Muffly, Lori S; Boulukos, Melissa; Swanson, Kate; Kocherginsky, Masha; Cerro, Paula Del; Schroeder, Linda; Pape, Lisa; Extermann, Martine; Van Besien, Koen; Artz, Andrew S

2013-03-01

Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Acyclovir-resistant herpes simplex virus 1 infection early after allogeneic hematopoietic stem cell transplantation with T-cell depletion.

Science.gov (United States)

Akahoshi, Yu; Kanda, Junya; Ohno, Ayumu; Komiya, Yusuke; Gomyo, Ayumi; Hayakawa, Jin; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Shiraki, Kimiyasu; Kanda, Yoshinobu

2017-07-01

We previously reported that oral low-dose acyclovir (200 mg/day) for the prevention of herpes simplex virus (HSV) infections after allogenic hematopoietic stem cell transplantation (HSCT) is effective without the emergence of acyclovir-resistant HSV infections. However, HSV infections are of significant concern because the number of allogeneic HSCT with T-cell depletion, which is a risk factor of the emergence of drug-resistant HSV infections, has been increasing. We experienced a 25-year-old female who received allogenic HSCT from an unrelated donor with 1-antigen mismatch using anti-thymocyte globulin. Despite acyclovir prophylaxis (200 mg/day), she developed the right palatal ulcer that was positive for HSV-1 specific antigen by fluorescent antibody on day 20 and developed new hypoglossal and tongue ulcers on day 33. Replacement of acyclovir with foscarnet improved her ulcers. We isolated 2 acyclovir-resistant and foscarnet-sensitive strains from the right palatal and hypoglossal ulcers, which had the same frame shift mutation in the thymidine kinase genes. The rate of proliferation of the isolate from the hypoglossal ulcer was faster than that from the right palatal ulcer in the plaque reduction assay. HSV strains that acquired acyclovir-resistant mutations at the right palatal ulcer with larger plaque might spread to the hypoglossal ulcer as the secondary site of infection because of better growth property. Second-line antiviral agents should be considered when we suspect treatment failure of HSV infection, especially in HSCT with T-cell depletion. Further studies are required whether low-dose acyclovir prophylaxis leads to the emergence of virological resistance. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Steroid-sparing effect of extracorporeal photopheresis in the therapy of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Ussowicz, M; Musiał, J; Mielcarek, M; Tomaszewska, A; Nasiłowska-Adamska, B; Kałwak, K; Gorczyńska, E; Mariańska, B; Chybicka, A

2013-11-01

Steroid-refractory graft-versus-host disease (GVHD) remains a challenging therapeutic problem after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical effect of extracorporeal photopheresis (ECP), and its impact on intensivity of immunosuppresive therapy in allogeneic HSCT patients. In this study 443 Therakos ECP procedures were performed in 21 patients after allogeneic HSCT with acute (aGVHD, 8 patients) or chronic (cGVHD, 13 patients) therapy-refractory GVHD. The median age at ECP onset was 20.5 years (range, 10-55). Venous access was provided by a nontunelized central venous catheter (12 patients) or 9.6-French portacath (9 patients). In the cGVHD group 9/13 patients were improved with a 4-year overall survival rate of 67.7%. ECP led to steroid discontinuation in 6 and substantial dose reduction in 5 patients. The prednisone dose equivalent per kilogram body weight decreased from 0.32 mg to 0.07 mg after therapy. Therapy of aGVHD led to complete or partial symptom remission in 3/9 subjects. The change in steroid dose in the aGVHD group was not significant, there were no long-term survivors. Portacath access was well tolerated and provided adequate blood flow rates. The ECP therapy significantly reduced the rates of remissions with steroid discontinuation among cGVHD but not aGVHD patients. Rare ECP-related complications were either catheter related or anticoagulation induced during ECP procedures. Photopheresis was a safe, effective method to treat steroid-resistant cGVHD. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Chimeric Human Skin Substitute Tissue: A Novel Treatment Option for the Delivery of Autologous Keratinocytes.

Science.gov (United States)

Rasmussen, Cathy A; Allen-Hoffmann, B Lynn

2012-04-01

For patients suffering from catastrophic burns, few treatment options are available. Chimeric coculture of patient-derived autologous cells with a "carrier" cell source of allogeneic keratinocytes has been proposed as a means to address the complex clinical problem of severe skin loss. Currently, autologous keratinocytes are harvested, cultured, and expanded to form graftable epidermal sheets. However, epidermal sheets are thin, are extremely fragile, and do not possess barrier function, which only develops as skin stratifies and matures. Grafting is typically delayed for up to 4 weeks to propagate a sufficient quantity of the patient's cells for application to wound sites. Fully stratified chimeric bioengineered skin substitutes could not only provide immediate wound coverage and restore barrier function, but would simultaneously deliver autologous keratinocytes to wounds. The ideal allogeneic cell source for this application would be an abundant supply of clinically evaluated, nontumorigenic, pathogen-free, human keratinocytes. To evaluate this potential cell-based therapy, mixed populations of a green fluorescent protein-labeled neonatal human keratinocyte cell line (NIKS) and unlabeled primary keratinocytes were used to model the allogeneic and autologous components of chimeric monolayer and organotypic cultures. Relatively few autologous keratinocytes may be required to produce fully stratified chimeric skin substitute tissue substantially composed of autologous keratinocyte-derived regions. The need for few autologous cells interspersed within an allogeneic "carrier" cell population may decrease cell expansion time, reducing the time to patient application. This study provides proof of concept for utilizing NIKS keratinocytes as the allogeneic carrier for the generation of bioengineered chimeric skin substitute tissues capable of providing immediate wound coverage while simultaneously supplying autologous human cells for tissue regeneration.

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...

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.

[Role of stem cell transplantation in treatment of primary cutaneous T‑cell lymphoma].

Science.gov (United States)

Stranzenbach, R; Theurich, S; Schlaak, M

2017-09-01

Within the heterogeneous group of cutaneous T‑cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. A literature search using the keywords "hematopoietic stem cell transplantation" and "cutaneous T‑cell lymphoma" was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T‑cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision.

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

Team dynamics, clinical work satisfaction, and patient care coordination between primary care providers: A mixed methods study.

Science.gov (United States)

Song, Hummy; Ryan, Molly; Tendulkar, Shalini; Fisher, Josephine; Martin, Julia; Peters, Antoinette S; Frolkis, Joseph P; Rosenthal, Meredith B; Chien, Alyna T; Singer, Sara J

Team-based care is essential for delivering high-quality, comprehensive, and coordinated care. Despite considerable research about the effects of team-based care on patient outcomes, few studies have examined how team dynamics relate to provider outcomes. The aim of this study was to examine relationships among team dynamics, primary care provider (PCP) clinical work satisfaction, and patient care coordination between PCPs in 18 Harvard-affiliated primary care practices participating in Harvard's Academic Innovations Collaborative. First, we administered a cross-sectional survey to all 548 PCPs (267 attending clinicians, 281 resident physicians) working at participating practices; 65% responded. We assessed the relationship of team dynamics with PCPs' clinical work satisfaction and perception of patient care coordination between PCPs, respectively, and the potential mediating effect of patient care coordination on the relationship between team dynamics and work satisfaction. In addition, we embedded a qualitative evaluation within the quantitative evaluation to achieve a convergent mixed methods design to help us better understand our findings and illuminate relationships among key variables. Better team dynamics were positively associated with clinical work satisfaction and quality of patient care coordination between PCPs. Coordination partially mediated the relationship between team dynamics and satisfaction for attending clinicians, suggesting that higher satisfaction depends, in part, on better teamwork, yielding more coordinated patient care. We found no mediating effects for resident physicians. Qualitative results suggest that sources of satisfaction from positive team dynamics for PCPs may be most relevant to attending clinicians. Improving primary care team dynamics could improve clinical work satisfaction among PCPs and patient care coordination between PCPs. In addition to improving outcomes that directly concern health care providers, efforts to

Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

Science.gov (United States)

Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

2017-10-01

Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

Barriers and facilitators influencing self-management among COPD patients: a mixed methods exploration in primary and affiliated specialist care

Directory of Open Access Journals (Sweden)

Hillebregt CF

2016-12-01

Full Text Available Chantal F Hillebregt,1 Auke J Vlonk,1 Marc A Bruijnzeels,1 Onno CP van Schayck,2 Niels H Chavannes3 1Jan van Es Institute (JVEI, Netherlands Expert Center Integrated Primary Care, Almere, 2Department of General Practice, School for Public Health and Primary Care (CAPHRI, Maastricht University Medical Center, Maastricht, 3Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands Abstract: Self-management is becoming increasingly important in COPD health care although it remains difficult to embed self-management into routine clinical care. The implementation of self-management is understood as a complex interaction at the level of patient, health care provider (HCP, and health system. Nonetheless there is still a poor understanding of the barriers and effective facilitators. Comprehension of these determinants can have significant implications in optimizing self-management implementation and give further directions for the development of self-management interventions. Data were collected among COPD patients (N=46 and their HCPs (N=11 in three general practices and their collaborating affiliated hospitals. Mixed methods exploration of the data was conducted and collected by interviews, video-recorded consultations (N=50, and questionnaires on consultation skills. Influencing determinants were monitored by 1 interaction and communication between the patient and HCP, 2 visible and invisible competencies of both the patient and the HCP, and 3 degree of embedding self-management into the health care system. Video observations showed little emphasis on effective behavioral change and follow-up of given lifestyle advice during consultation. A strong presence of COPD assessment and monitoring negatively affects the patient-centered communication. Both patients and HCPs experience difficulties in defining personalized goals. The satisfaction of both patients and HCPs concerning patient centeredness during

Factors associated with the utilization of primary care emergency centers in a Spanish region with high population dispersion: a mixed-methods study.

Science.gov (United States)

Sanz-Barbero, Belén; Otero-García, Laura; Blasco-Hernández, Teresa; San Sebastián, Miguel

2014-09-03

Adequate access to primary care emergency centers is particularly important in rural areas isolated from urban centers. However, variability in utilization of emergency services located in primary care centers among inhabitants of nearby geographical areas is understudied. The objectives of this study are twofold: 1) to analyze the association between the availability of municipal emergency care centers and utilization of primary care emergency centers (PCEC), in a Spanish region with high population dispersion; and 2) to determine healthcare providers' perceptions regarding PCEC utilization. A mixed-methods study was conducted. Quantitative phase: multilevel logistic regression modeling using merged data from the 2003 Regional Health Survey of Castile and Leon and the 2001 census data (Spain). Qualitative phase:14 in-depth- interviews of rural-based PCEC providers. Having PCEC as the only emergency center in the municipality was directly associated with its utilization (p use. PCEC users were considered to be predominantly workers and students with scheduling conflicts with rural primary care opening hours. The location of emergency care centers is associated with PCEC utilization. Increasing access to primary care by extending hours may be an important step toward optimal PCEC utilization. Further research would determine whether lower PCEC use by certain groups is associated with disparities in access to care.

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...

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)

Primary care physicians' perceived barriers and facilitators to conservative care for older adults with chronic kidney disease: design of a mixed methods study.

Science.gov (United States)

Tam-Tham, Helen; Hemmelgarn, Brenda; Campbell, David; Thomas, Chandra; Quinn, Robert; Fruetel, Karen; King-Shier, Kathryn

2016-01-01

Guideline committees have identified the need for research to inform the provision of conservative care for older adults with stage 5 chronic kidney disease (CKD) who have a high burden of comorbidity or functional impairment. We will use both qualitative and quantitative methodologies to provide a comprehensive understanding of barriers and facilitators to care for these patients in primary care. Our objectives are to (1) interview primary care physicians to determine their perspectives of conservative care for older adults with stage 5 CKD and (2) survey primary care physicians to determine the prevalence of key barriers and facilitators to provision of conservative care for older adults with stage 5 CKD. A sequential exploratory mixed methods design was adopted for this study. The first phase of the study will involve fundamental qualitative description and the second phase will be a cross-sectional population-based survey. The research is conducted in Alberta, Canada. The participants are primary care physicians with experience in providing care for older adults with stage 5 CKD not planning on initiating dialysis. The first objective will be achieved by undertaking interviews with primary care physicians from southern Alberta. Participants will be selected purposively to include physicians with a range of characteristics (e.g., age, gender, and location of clinical practice). Interviews will be recorded, transcribed verbatim, and analyzed using conventional content analysis to generate themes. The second objective will be achieved by undertaking a population-based survey of primary care physicians in Alberta. The questionnaire will be developed based on the findings from the qualitative interviews and pilot tested for face and content validity. Physicians will be provided multiple options to complete the questionnaire including mail, fax, and online methods. Descriptive statistics and associations between demographic factors and barriers and facilitators to

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.

Scoping Study of Airlift Circulation Technologies for Supplemental Mixing in Pulse Jet Mixed Vessels

Energy Technology Data Exchange (ETDEWEB)

Schonewill, Philip P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Berglin, Eric J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Boeringa, Gregory K. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Buchmiller, William C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Burns, Carolyn A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Minette, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2015-04-07

At the request of the U.S. Department of Energy Office of River Protection, Pacific Northwest National Laboratory (PNNL) conducted a scoping study to investigate supplemental technologies for supplying vertical fluid motion and enhanced mixing in Waste Treatment and Immobilization Plant (WTP) vessels designed for high solids processing. The study assumed that the pulse jet mixers adequately mix and shear the bottom portion of a vessel. Given that, the primary function of a supplemental technology should be to provide mixing and shearing in the upper region of a vessel. The objective of the study was to recommend a mixing technology and configuration that could be implemented in the 8-ft test vessel located at Mid-Columbia Engineering (MCE). Several mixing technologies, primarily airlift circulator (ALC) systems, were evaluated in the study. This technical report contains a review of ALC technologies, a description of the PNNL testing and accompanying results, and recommended features of an ALC system for further study.

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...

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...

Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

International Nuclear Information System (INIS)

Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M.

2008-01-01

Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Energy Technology Data Exchange (ETDEWEB)

Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. [Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany)

2008-12-15

Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

Computed Tomography Findings of Human Polyomavirus BK (BKV)-Associated Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

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Schulze, M.; Beck, R.; Igney, A.; Vogel, M.; Maksimovic, O.; Claussen, C.D.; Faul, C.; Horger, M. (Dept. of Diagnostic Radiology, Dept. of Internal Medicine-Oncology, and Inst. of Medical Virology, Eberhard-Karls Univ., Tbingen (Germany))

2008-12-15

Background: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. Purpose: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). Material and Methods: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. Results: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. Conclusion: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and

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.

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.

Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies.

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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.

A mixed-methods examination of communication between oncologists and primary care providers among primary care physicians in underserved communities.

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Shen, Megan Johnson; Binz-Scharf, Maria; D'Agostino, Tom; Blakeney, Natasha; Weiss, Elisa; Michaels, Margo; Patel, Shilpa; McKee, M Diane; Bylund, Carma L

2015-03-15

Research has demonstrated that communication and care coordination improve cancer patient outcomes. To improve communication and care coordination, it is important to understand primary care providers' (PCPs') perceptions of communication with oncologists as well as PCPs' communication needs. A mixed-methods approach was used in the present study. In the qualitative phase of the study, 18 PCPs practicing in underserved, minority communities were interviewed about their experiences communicating with oncologists. In the quantitative phase of the study, 128 PCPs completed an online survey about their preferences, experiences, and satisfaction with communication with oncologists. Results indicated a PCP-oncologist gap in communication occurred between diagnosis and treatment. PCPs wanted more communication with oncologists, updates on their patients' prognosis throughout treatment, and to be contacted via telephone or email and saw their role as crucial in providing supportive care for their patients. Although PCPs recognize that they play a critical, proactive role in supporting patients throughout the continuum of their cancer care experience, existing norms regarding postreferral engagement and oncologist-PCP communication often hinder activation of this role among PCPs. Expected standards regarding the method, frequency, and quality of postreferral communication should be jointly articulated and made accountable between PCPs and oncologists to help improve cancer patients' quality of care, particularly in minority communities. © 2014 American Cancer Society.

Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

DEFF Research Database (Denmark)

Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham

2009-01-01

OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed...... of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...

ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

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Li, Junjie; Xie, Jiangang; Liu, Shanshou; Li, Xiao; Zhang, Dongliang; Wang, Xianqi; Jiang, Jinquan; Hu, Wei; Zhang, Yuan; Jin, Boquan; Zhuang, Ran; Yin, Wen

2018-04-25

ADAR1 (adenosine deaminase acting on double-stranded RNA 1) is an RNA-editing enzyme that mediates adenosine-to-inosine RNA editing events, an important post-transcriptional modification mechanism that can alter the coding properties of mRNA or regulate microRNA biogenesis. ADAR1 also regulates the innate immune response. Here, we have demonstrated that ADAR1 expression increased in LPS-stimulated macrophages. Silencing ADAR1 by using small interfering RNA in macrophages resulted in the pronounced polarization of macrophages to M1, whereas ADAR1 overexpression promoted M2 polarization, which indicated that ADAR1 can inhibit macrophage hyperpolarization and prevent immune hyperactivity. The RNA-RNP immunoprecipitation binding assay demonstrated a direct interaction between ADAR1 and miR-21 precursor. Significant up-regulation in IL-10 and down-regulation in miR-21 were observed in ADAR1-overexpressing macrophages. We evaluated miR-21 target mRNAs and macrophage polarization signaling pathways and found that forkhead box protein O1 (Foxo1) was up-regulated in cells that overexpressed ADAR1. In a mouse allogeneic skin transplantation model, grafts in the ADAR1-overexpressed group survived longer and suffered less immune cell infiltration. In ADAR1-overexpressed recipients, splenic macrophages were significantly polarized to M2, and levels of sera IL-10 were markedly higher than those in the control group. In summary, ADAR1 modulates macrophage M2 polarization via the ADAR1-miR-21-Foxo1-IL-10 axis, thereby suppressing allogeneic graft rejection.-Li, J., Xie, J., Liu, S., Li, X., Zhang, D., Wang, X., Jiang, J., Hu, W., Zhang, Y., Jin, B., Zhuang, R., Yin, W. ADAR1 attenuates allogeneic graft rejection by suppressing miR-21 biogenesis in macrophages and promoting M2 polarization.

Addition of exogenous cytokines in mixed lymphocyte culture for selecting related donors for bone marrow transplantation

Directory of Open Access Journals (Sweden)

Jeane Eliete Laguila Visentainer

Full Text Available CONTEXT: Mixed lymphocyte culturing has led to conflicting opinions regarding the selection of donors for bone marrow transplantation. The association between a positive mixed lymphocyte culture and the development of graft-versus-host disease (GVHD is unclear. The use of exogenous cytokines in mixed lymphocyte cultures could be an alternative for increasing the sensitivity of culture tests. OBJECTIVE: To increase the sensitivity of mixed lymphocyte cultures between donor and recipient human leukocyte antigen (HLA identical siblings, using exogenous cytokines, in order to predict post-transplantation GVHD and/or rejection. TYPE OF STUDY: Prospective study. SETTING: Bone Marrow Transplantation Unit, Universidade Estadual de Campinas. PARTICIPANTS: Seventeen patients with hematological malignancies and their respective donors selected for bone marrow transplantation procedures. PROCEDURES: Standard and modified mixed lymphocyte culturing by cytokine supplementation was carried out using donor and recipient cells typed for HLA. MAIN MEASUREMENTS: Autologous and allogenic responses in mixed lymphocyte cultures after the addition of IL-4 or IL-2. RESULTS: In comparison with the standard method, average responses in the modified mixed lymphocyte cultures increased by a factor of 2.0 using IL-4 (p < 0.001 and 6.4 using IL-2 (p < 0.001, for autologous donor culture responses. For donor-versus-recipient culture responses, the increase was by a factor of 1.9 using IL-4 (p < 0.001 and 4.1 using IL-2 (p < 0.001. For donor-versus-unrelated culture responses, no significant increase was observed using IL-4, and a mean response inhibition of 20% was observed using IL-2 (p < 0.001. Neither of the cytokines produced a significant difference in the unrelated control versus recipient cell responses. CONCLUSION: IL-4 supplementation was the best for increasing the mixed lymphocyte culture sensitivity. However, IL-4 also increased autologous responses, albeit less

Use of a case-mix approach to study the trends in the incidence of second primary cancers.

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Gass, Boris; Marrer, Emilie; Bara, Simona; Ligier, Karine; Molinié, Florence; Colonna, Marc; Daubisse-Marliac, Laetitia; Trétarre, Brigitte; Lapôtre-Ledoux, Bénédicte; Woronoff, Anne-Sophie; Guizard, Anne-Valérie; Bouvier, Véronique; Troussard, Xavier; Gaiddon, Christian; Klein, Delphine; Velten, Michel; Jégu, Jérémie

2018-05-01

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution. Cases registered by 13 French cancer registries between 1989 and 2010 and followed-up until June 2013 were included. The person-year approach was used to compute standardized incidence ratios (SIRs) of metachronous SPC. Usual SIRs and cancer site-specific weighted SIRs called "case-mix SIRs" (cmSIRs) were estimated by sex and calendar period of first cancer diagnosis. Calendar trends in SIRs and cmSIRs were compared. More than 2.9 million person-years at risk were included. Among males, SIRs dropped from 1.49 to 1.23 between 1989-1994 and 2005-2010, while cmSIRs decreased from 1.40 to 1.27. This difference seems mainly related to a stronger representation of prostate cancers (at lower risk of SPC) and a weaker contribution of bladder and head and neck cancers (at higher risk of SPC) in recent periods of diagnosis. Among females, both SIRs and cmSIRs have remained stable at around 1.22 and 1.21, respectively. The cmSIR is an indicator that is not influenced by changes in first cancer site distribution. Its use should be encouraged to assess second cancer incidence control. Copyright © 2018 Elsevier Inc. All rights reserved.

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...

Successful treatment with chemotherapy and subsequent allogeneic bone marrow transplantation for myeloid blastic crisis of chronic myelogenous leukemia following advanced Hodgkin's disease

NARCIS (Netherlands)

Punt, C. J.; Rozenberg-Arska, M.; Verdonck, L. F.

1987-01-01

A 33-year-old man was treated with intensive chemotherapy for myeloid blastic crisis of chronic myelogenous leukemia (CML), which developed after radiotherapy and chemotherapy for Hodgkin's disease. After achieving a second chronic phase, he underwent allogeneic bone marrow transplantation (BMT).

Leveraging quality improvement through use of the Systems Assessment Tool in Indigenous primary health care services: a mixed methods study.

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Cunningham, Frances C; Ferguson-Hill, Sue; Matthews, Veronica; Bailie, Ross

2016-10-18

Assessment of the quality of primary health care health delivery systems is a vital part of continuous quality improvement (CQI) processes. The Systems Assessment Tool (SAT) was designed to support Indigenous PHC services in assessing and improving their health care systems. It was based on the Assessment of Chronic Illness Care scale, and on practical experience with applying systems assessments in quality improvement in Indigenous primary health care. We describe the development and application of the SAT, report on a survey to assess the utility of the SAT and review the use of the SAT in other CQI research programs. The mixed methods approach involved a review of documents and internal reports relating to experience with use of the SAT since its development in 2002 and a survey of key informants on their experience with using the SAT. The paper drew from documents and internal reports to describe the SAT development and application in primary health care services from 2002 to 2014. Survey feedback highlighted the benefit to the whole primary health care team from participating in the SAT, bringing to light issues that might not emerge with separate individual tool completion. A majority of respondents reported changes in their health centres as a result of using the SAT. Good organisational and management support assisted with ensuring allocation of time and resources for SAT conduct. Respondents identified the importance of having a skilled, external facilitator. Originally designed as a measurement tool, the SAT rapidly evolved to become an important development tool, assisting teams in learning about primary health care system functioning, applying best practice and contributing to team strengthening. It is valued by primary health care centres as a lever in implementing improvements to strengthen centre delivery systems, and has potential for further adaptation and wider application in Australia and internationally.

Outcome in hip fracture patients related to anemia at admission and allogeneic blood transfusion: An analysis of 1262 surgically treated patients

NARCIS (Netherlands)

A.J.H. Vochteloo (Anne); B.L. Borger van der Burg (Boudewijn); B. Mertens (Bart); A.H.P. Niggebrugge (Arthur); M.R. de Vries (Mark); W.E. Tuinebreijer (Wim); R.M. Bloem (Rolf); R.G.H.H. Nelissen (Rob); P. Pilot (Peter)

2011-01-01

textabstractBackground: Anemia is more often seen in older patients. As the mean age of hip fracture patients is rising, anemia is common in this population. Allogeneic blood transfusion (ABT) and anemia have been pointed out as possible risk factors for poorer outcome in hip fracture patients.

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.

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.

Y chromosome and vimentin used to trace the fate of allogeneic keratinocytes delivered to the wound by the recombined human/pig skin

Czech Academy of Sciences Publication Activity Database

Pokorná, Eva; Brož, L.; Veselý, Pavel; Matoušková, Eva

2001-01-01

Roč. 47, č. 4 (2001), s. 128-134 ISSN 0015-5500 R&D Projects: GA MZd IZ4368; GA MZd NK6126 Keywords : allogeneic keratinocytes * xenodermis * Y-chromosome FISH Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation

NARCIS (Netherlands)

J.W.J. van Esser (Joost); H.G.M. Niesters (Bert); B. van der Holt (Bronno); E. Meijer (Ellen); A.D.M.E. Osterhaus (Albert); J.W. Gratama (Jan-Willem); L.F. Verdonck (Leo); B. Löwenberg (Bob); J.J. Cornelissen (Jan)

2002-01-01

textabstractRecipients of a partially T-cell-depleted (TCD) allogeneic stem cell transplantation (allo-SCT) developing reactivation of Epstein-Barr virus (EBV) with quantified viral DNA levels exceeding 1000 genome equivalents/milliliter (geq/mL) are at high risk for EBV-lymphoproliferative disease

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

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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.

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.

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....

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

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Sydney X Lu

Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

Reduction in allogeneic blood products with routine use of autotransfusion in open elective infrarenal abdominal aortic aneurysm repair.

Science.gov (United States)

Courtemanche, Karim; Elkouri, Stephane; Dugas, Jean-Philippe; Beaudoin, Nathalie; Bruneau, Luc; Blair, Jean-François

2013-11-01

Concern about allogeneic blood product cost and complications has prompted interest in blood conservation techniques. Intraoperative autotransfusion (IAT) is currently not used routinely by vascular surgeons in open elective infrareanl abdominal aortic aneurysm (AAA) repair. The objective of this study is to review our experience with IAT and its impact on blood transfusion. We retrospectively reviewed the medical records of consecutive patients treated electively over a 4-year period and compared 2 strategy related to IAT, routine use IAT (rIAT) versus on-demand IAT (oIAT). Outcomes measured were number of units of allogeneic red blood cells and autologous red blood cells transfused intraoperatively and postoperatively, preoperative, postoperative, and discharge hemoglobin levels; postoperative infections; length of postoperative intensive care stay; and length of hospital stay. T-independent and Fisher exact test were used. A total of 212 patients were included, 38 (18%) in the rIAT and 174 (82%) in the oIAT. Groups were similar except for an inferior creatinine and a superior mean aneurysm diameter for the rIAT group. Patients in the rIAT group had a lower rate of transfusion (26% vs 54%, P = .002) and a lower mean number of blood unit transfused (0.8 vs 1.8, P = .048). These findings were still more significant for AAA larger than 60 mm (18% rIAT vs 62% oIAT, P = .0001). Postoperative hemoglobin was superior in the rIAT group (107 vs 101 g/L, P = .01). Mean postoperative intensive care length of stay was shorter for the rIAT group (1.1 vs 1.8 days, P = .01). No difference was noted for infection, mortality, or hospital length of stay. The rIAT reduced the exposure to allogeneic blood products by more than 50%, in particular for patients with AAA larger than 60 mm. These results support the use of rIAT for open elective infrarenal AAA repair.

Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure.

Science.gov (United States)

Smith, Sonali M; Godfrey, James; Ahn, Kwang Woo; DiGilio, Alyssa; Ahmed, Sairah; Agrawal, Vaibhav; Bachanova, Veronika; Bacher, Ulrike; Bashey, Asad; Bolaños-Meade, Javier; Cairo, Mitchell; Chen, Andy; Chhabra, Saurabh; Copelan, Edward; Dahi, Parastoo B; Aljurf, Mahmoud; Farooq, Umar; Ganguly, Siddhartha; Hertzberg, Mark; Holmberg, Leona; Inwards, David; Kanate, Abraham S; Karmali, Reem; Kenkre, Vaishalee P; Kharfan-Dabaja, Mohamed A; Klein, Andreas; Lazarus, Hillard M; Mei, Matthew; Mussetti, Alberto; Nishihori, Taiga; Ramakrishnan Geethakumari, Praveen; Saad, Ayman; Savani, Bipin N; Schouten, Harry C; Shah, Nirav; Urbano-Ispizua, Alvaro; Vij, Ravi; Vose, Julie; Sureda, Anna; Hamadani, Mehdi

2018-04-12

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated. This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM). Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

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....

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.

Advancing towards commonsense regulation of mixed waste: Regulatory update

International Nuclear Information System (INIS)

Porter, C.L.

1996-01-01

The author previously presented the basis for regulating mixed waste according to the primary hazard (either chemical or radiological) in order to avoid the inefficient practice of open-quotes dual regulationclose quotes of mixed waste. In addition to covering the technical basis, recommendations were made on how to capitalize upon a window of opportunity for implementation of a open-quotes primary hazards approachclose quotes. Some of those recommendations have been pursued and the resulting advances on the regulatory front are exciting. This paper chronicles those pursuits, presents in capsule form the massive amount of data assembled, and summarizes the changing regulatory framework. The data supports the premise that disposal of stabilized mixed waste in a low-level radioactive waste (LLW) disposal facility is protective of human health and the environment. Based on that premise, proposed regulatory changes, if finalized, will eliminate much of the open-quotes dual regulationclose quotes of mixed waste

Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study

NARCIS (Netherlands)

Raber-Durlacher, Judith E.; Laheij, Alexa M. G. A.; Epstein, Joel B.; Epstein, Matthew; Geerligs, Gerard M.; Wolffe, Gordon N.; Blijlevens, Nicole M. A.; Donnelly, J. Peter

2013-01-01

This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT).

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.

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

[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.

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

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

Science.gov (United States)

Ronald, John A; Kim, Byung-Su; Gowrishankar, Gayatri; Namavari, Mohammad; Alam, Israt S; D'Souza, Aloma; Nishikii, Hidekazu; Chuang, Hui-Yen; Ilovich, Ohad; Lin, Chih-Feng; Reeves, Robert; Shuhendler, Adam; Hoehne, Aileen; Chan, Carmel T; Baker, Jeanette; Yaghoubi, Shahriar S; VanBrocklin, Henry F; Hawkins, Randall; Franc, Benjamin L; Jivan, Salma; Slater, James B; Verdin, Emily F; Gao, Kenneth T; Benjamin, Jonathan; Negrin, Robert; Gambhir, Sanjiv Sam

2017-06-01

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR . ©2017 American Association for Cancer Research.

Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

DEFF Research Database (Denmark)

Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

2013-01-01

Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin and celeco......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

Food safety knowledge, practices and beliefs of primary food preparers in families with young children. A mixed methods study.

Science.gov (United States)

Meysenburg, Rebecca; Albrecht, Julie A; Litchfield, Ruth; Ritter-Gooder, Paula K

2014-02-01

Food preparers in families with young children are responsible for safe food preparation and handling to prevent foodborne illness. To explore the food safety perceptions, beliefs, and practices of primary food preparers in families with children 10 years of age and younger, a mixed methods convergent parallel design and constructs of the Health Belief Model were used. A random sampling of 72 primary food handlers (36.2±8.6 years of age, 88% female) within young families in urban and rural areas of two Midwestern states completed a knowledge survey and participated in ten focus groups. Quantitative data were analyzed using SPSS. Transcribed interviews were analyzed for codes and common themes. Forty-four percent scored less than the average knowledge score of 73%. Participants believe children are susceptible to foodborne illness but perceive its severity to be low with gastrointestinal discomfort as the primary outcome. Using safe food handling practices and avoiding inconveniences were benefits of preventing foodborne illness. Childcare duties, time and knowledge were barriers to practicing food safety. Confidence in preventing foodborne illness was high, especially when personal control over food handling is present. The low knowledge scores and reported practices revealed a false sense of confidence despite parental concern to protect their child from harm. Food safety messages that emphasize the susceptibility and severity of foodborne illness in children are needed to reach this audience for adoption of safe food handling practices. Published by Elsevier Ltd.

Who is on the primary care team? Professionals' perceptions of the conceptualization of teams and the underlying factors: a mixed-methods study.

Science.gov (United States)

Doekhie, Kirti D; Buljac-Samardzic, Martina; Strating, Mathilde M H; Paauwe, Jaap

2017-12-28

Due to the growing prevalence of elderly patients with multi-morbidity living at home, there is an increasing need for primary care professionals from different disciplinary backgrounds to collaborate as primary care teams. However, it is unclear how primary care professionals conceptualize teams and what underlying factors influence their perception of being part of a team. Our research question is: What are primary care professionals' perceptions of teams and team membership among primary care disciplines and what factors influence their perceptions? We conducted a mixed-methods study in the Dutch primary care setting. First, a survey study of 152 professionals representing 12 primary care disciplines was conducted, focusing on their perceptions of which disciplines are part of the team and the degree of relational coordination between professionals from different disciplinary backgrounds. Subsequently, we conducted semi-structured interviews with 32 professionals representing 5 primary care disciplines to gain a deeper understanding of the underlying factors influencing their perceptions and the (mis)alignment between these perceptions. Misalignments were found between perceptions regarding which disciplines are members of the team and the relational coordination between disciplines. For example, general practitioners were viewed as part of the team by helping assistants, (district) nurses, occupational therapists and geriatric specialized practice nurses, whereas the general practitioners themselves only considered geriatric specialized practice nurses to be part of their team. Professionals perceive multidisciplinary primary care teams as having multiple inner and outer layers. Three factors influence their perception of being part of a team and acting accordingly: a) knowing the people you work with, b) the necessity for knowledge exchange and c) sharing a holistic view of caregiving. Research and practice should take into account the misalignment between

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.

Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogeneic donations.

Science.gov (United States)

Zou, Shimian; Stramer, Susan L; Dodd, Roger Y

2012-04-01

Over the past 20 years, there has been a major increase in the safety of the blood supply, as demonstrated by declining rates of posttransfusion infection and reductions in estimated residual risk for such infections. Reliable estimates of residual risk have been possible within the American Red Cross system because of the availability of a large amount of reliable and consistent data on donations and infectious disease testing results. Among allogeneic blood donations, the prevalence rates of infection markers for hepatitis C virus (HCV) and hepatitis B virus have decreased over time, although rates for markers of human immunodeficiency virus (HIV) and human T-cell lymphotropic virus did not. The incidence (/100 000 person-years) of HIV and HCV among repeat donors showed apparent increases from 1.55 and 1.89 in 2000 through 2001 to 2.16 and 2.98 in 2007 through 2008. These observed fluctuations confirm the need for continuous monitoring and evaluation. The residual risk of HIV, HCV, and human T-cell lymphotropic virus among all allogeneic donations is currently below 1 per 1 million donations, and that of hepatitis B surface antigen is close to 1 per 300 000 donations. Copyright © 2012 Elsevier Inc. All rights reserved.

T-cell chimerism is valuable in predicting early mortality in steroid-resistant acute graft-versus-host disease after myeloablative allogeneic cell transplantation

DEFF Research Database (Denmark)

Minculescu, Lia; Madsen, Hans O.; Sengeløv, Henrik

2014-01-01

The main aim of this study was to evaluate the impact of early T-cell chimerism status on the incidence and clinical course of acute graft-versus-host disease (aGVHD) in allogeneic transplant recipients after myeloablative conditioning. Of 62 patients, 38 (61%) had complete T-cell donor chimerism...

Humor Climate of the Primary Schools

Science.gov (United States)

Sahin, Ahmet

2018-01-01

The aim of this study is to determine the opinions primary school administrators and teachers on humor climates in primary schools. The study was modeled as a convergent parallel design, one of the mixed methods. The data gathered from 253 administrator questionnaires, and 651 teacher questionnaires was evaluated for the quantitative part of the…

Combustor with two stage primary fuel tube with concentric members and flow regulating

Science.gov (United States)

Parker, David Marchant; Whidden, Graydon Lane; Zolyomi, Wendel

1999-01-01

A combustor for a gas turbine having a centrally located fuel nozzle and inner, middle and outer concentric cylindrical liners, the inner liner enclosing a primary combustion zone. The combustor has an air inlet that forms two passages for pre-mixing primary fuel and air to be supplied to the primary combustion zone. Each of the pre-mixing passages has a circumferential array of swirl vanes. A plurality of primary fuel tube assemblies extend through both pre-mixing passages, with each primary fuel tube assembly located between a pair of swirl vanes. Each primary fuel tube assembly is comprised of two tubular members. The first member supplies fuel to the first pre-mixing passage, while the second member, which extends through the first member, supplies fuel to the second pre-mixing passage. An annular fuel manifold is divided into first and second chambers by a circumferentially extending baffle. The proximal end of the first member is attached to the manifold itself while the proximal end of the second member is attached to the baffle. The distal end of the first member is attached directly to the second member at around its mid-point. The inlets of the first and second members are in flow communication with the first and second manifold chambers, respectively. Control valves separately regulate the flow of fuel to the two chambers and, therefore, to the two members of the fuel tube assemblies, thereby allowing the flow of fuel to the first and second pre-mixing passages to be separately controlled.

Allogenic controls on the fluvial architecture and fossil preservation of the Upper Triassic Ischigualasto Formation, NW Argentina

Science.gov (United States)

Colombi, Carina E.; Limarino, Carlos O.; Alcober, Oscar A.

2017-12-01

The Upper Triassic Ischigualasto Formation in NW Argentina was deposited in a fluvial system during the synrift filling of the extensional Ischigualasto-Villa Unión Basin. The expansive exposures of the fluvial architecture and paleosols provide a framework to reconstruct the paleoenvironmental evolution of this basin during the Upper Triassic using continental sequence stratigraphy. The Ischigualasto Formation deposition can be divided into seven sequential sedimentary stages: the 1) Bypass stage; 2) Confined low-accommodation stage; 3) Confined high accommodation stage; 4) Unstable-accommodation stage; 5) Unconfined high-accommodation stage; 6) Unconfined low-accommodation stage; and finally, 7) Unconfined high-accommodation stage. The sedimentary evolution of the Ischigualasto Formation was driven by different allogenic controls such as rises and falls in lake levels, local tectonism, subsidence, volcanism, and climate, which also produced modifications of the equilibrium profile of the fluvial systems. All of these factors result in different accommodations in central and flank areas of the basin, which led to different architectural configurations of channels and floodplains. Allogenic processes affected not only the sequence stratigraphy of the basin but also the vertebrate and plant taphocenosis. Therefore, the sequence stratigraphy can be used not only as a predictive tool related to fossil occurrence but also to understand the taphonomic history of the basin at each temporal interval.

Non-myeloablative allogeneic stem cell transplantation focusing on immunotherapy of life-threatening malignant and non-malignant diseases.

Science.gov (United States)

Slavin, S; Nagler, A; Shapira, M; Panigrahi, S; Samuel, S; Or, A

2001-01-01

Allogeneic bone marrow transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion (DLI) following BMT. Thus, eradication of blood cancer cells, especially in patients with CML can be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. The latter working hypothesis suggested that effective BMT procedures may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that safe non-myeloablative stem cell transplantation (NST), with no major toxicity can replace the conventional BMT. Thus, NST may provide an option for cure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality.

Fluvial terrace formation in the northern Upper Rhine Graben during the last 20 000 years as a result of allogenic controls and autogenic evolution

NARCIS (Netherlands)

Erkens, G.; Dambeck, R.; Volleberg, K.P.; Bouman, M.I.T.J.; Bos, J.A.A.; Cohen, K.M.; Hoek, W.Z.

2009-01-01

The northern Upper Rhine Graben hosts a well-preserved Late Weichselian and Holocene fluvial terrace sequence. Terraces differ in elevation, morphology, and overbank sediment characteristics. The purpose of this study was to determine the relative importance of allogenic controlling factors versus

[Occlusal anomalies in the deciduous and mixed bites].

Science.gov (United States)

Legovic, M; Mady, L

1998-01-01

In 311 examines (177 boys and 134 girls) with primary dentition and 535 examinees (285 boys and 250 girls) with mixed dentition in Istria--Croatia, the frequency of orthodontic and occlusive anomalies in regard of space plane and premature extraction of c, m1 and m2 are investigated. The orthodontic anomalies are defected in 46.95%, premature loss in 11.25% and occlusive anomalies in 40.85% of examinees with primary dentition, while in mixed dentition the 58.69% of examinees have orthodontic anomaly, the 17.20% premature loss and the 48.97% of examinees have occlusal anomaly. In both phases of dentition the most frequent are occlusive anomalies in the following planes: sagittal, vertical and sagittal-vertical.

Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures

Directory of Open Access Journals (Sweden)

Terro F

2011-06-01

Full Text Available Abstract Background Inflammation may be involved in the pathogenesis of Alzheimer's disease (AD. There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by β-amyloid (Aβ peptides, the nuclear factor-kappa B (NF-κB pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aβ42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia. Methods Primary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aβ neurotoxicity (72 h, co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα, interleukin (IL-1β, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc test Results In these co-cultures, PKR inhibition prevented Aβ42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα and interleukin (IL-1β, and limited apoptosis. Conclusion In spite of the

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

A non-fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient.

Science.gov (United States)

Eickhardt, Steffen; Braendstrup, Peter; Clasen-Linde, Erik; Jensen, Karl E; Alhede, Morten; Bjarnsholt, Thomas; Høiby, Niels; Vindeløv, Lars; Moser, Claus

2013-05-01

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. © 2012 The Authors APMIS © 2012 APMIS.

Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease.

Science.gov (United States)

Dignan, F; Gujral, D; Ethell, M; Evans, S; Treleaven, J; Morgan, G; Potter, M

2007-07-01

Veno-occlusive disease (VOD) is a common and high-risk complication of allogeneic stem cell transplantation (SCT). Defibrotide has recently been used successfully to treat the disorder. We report on 58 patients who received defibrotide prophylaxis without concurrent heparin. No patients fulfilled the Baltimore criteria for VOD or died of the condition within 100 days of SCT. None of this group developed haemorrhagic complications secondary to defibrotide. These observations suggest that prophylaxis with defibrotide alone may reduce the incidence of VOD post-SCT although a randomised controlled trial is warranted to further evaluate its role.

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....

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

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 ...

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.).

Immature dendritic cells generated from cryopreserved human monocytes show impaired ability to respond to LPS and to induce allogeneic lymphocyte proliferation.

Directory of Open Access Journals (Sweden)

Guilherme Ferreira Silveira

Full Text Available Dendritic cells play a key role in the immune system, in the sensing of foreign antigens and triggering of an adaptive immune response. Cryopreservation of human monocytes was investigated to understand its effect on differentiation into immature monocyte-derived dendritic cells (imdDCs, the response to inflammatory stimuli and the ability to induce allogeneic lymphocyte proliferation. Cryopreserved (crp-monocytes were able to differentiate into imdDCs, albeit to a lesser extent than freshly (frh-obtained monocytes. Furthermore, crp-imdDCs had lower rates of maturation and cytokine/chemokine secretion in response to LPS than frh-imdDCs. Lower expression of Toll-like receptor 4 (at 24 and 48 h and higher susceptibility to apoptosis in crp-imdDCs than in fresh cells would account for the impaired maturation and cytokine/chemokine secretion observed. A mixed leukocyte reaction showed that lymphocyte proliferation was lower with crp-imdDCs than with frh-imdDCs. These findings suggested that the source of monocytes used to generate human imdDCs could influence the accuracy of results observed in studies of the immune response to pathogens, lymphocyte activation, vaccination and antigen sensing. It is not always possible to work with freshly isolated monocytes but the possible effects of freezing/thawing on the biology and responsiveness of imdDCs should be taken into account.

Impact of postremission consolidation chemotherapy on outcome after reduced-intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission

DEFF Research Database (Denmark)

Yeshurun, Moshe; Labopin, Myriam; Blaise, Didier

2014-01-01

The objective of the current study was to investigate the role of postremission consolidation chemotherapy before reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (alloSCT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1)....

Highly Efficient Stable Expression of Indoleamine 2,3 Dioxygenase Gene in Primary Fibroblasts

Directory of Open Access Journals (Sweden)

Rezakhanlou Alireza

2010-03-01

Full Text Available Abstract Indoleamine 2,3 dioxygenase (IDO is a potent immunomodulatory enzyme that has recently attracted significant attention for its potential application as an inducer of immunotolerance in transplantation. We have previously demonstrated that a collagen matrix populated with IDO-expressing fibroblasts can be applied successfully in suppressing islet allogeneic immune response. Meanwhile, a critical aspect of such immunological intervention relies largely on effective long-term expression of the IDO gene. Moreover, gene manipulation of primary cells is known to be challenging due to unsatisfactory expression of the exogenous gene. In this study, a lentiviral gene delivery system has been employed to transduce primary fibroblasts. We used polybrene to efficiently deliver the IDO gene into primary fibroblasts and showed a significant increase (about tenfold in the rate of gene transfection. In addition, by the use of fluorescence-activated cell sorting, a 95% pure population of IDO-expressing fibroblasts was successfully obtained. The efficiency of the IDO expression and the activity of the enzyme have been confirmed by Western blotting, fluorescence-activated cell sorting analysis, and Kynurenine assay, respectively. The findings of this study revealed simple and effective strategies through which an efficient and stable expression of IDO can be achieved for primary cells which, in turn, significantly improves its potential as a tool for achieving immunotolerance in different types of transplantation.

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....

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

Science.gov (United States)

Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

2016-04-01

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

Carbon footprint of patient journeys through primary care: a mixed methods approach.

Science.gov (United States)

Andrews, Elizabeth; Pearson, David; Kelly, Charlotte; Stroud, Laura; Rivas Perez, Martin

2013-09-01

The NHS has a target of cutting its carbon dioxide (CO2) emissions by 80% below 1990 levels by 2050. Travel comprises 17% of the NHS carbon footprint. This carbon footprint represents the total CO2 emissions caused directly or indirectly by the NHS. Patient journeys have previously been planned largely without regard to the environmental impact. The potential contribution of 'avoidable' journeys in primary care is significant. To investigate the carbon footprint of patients travelling to and from a general practice surgery, the issues involved, and potential solutions for reducing patient travel. A mixed methods study in a medium-sized practice in Yorkshire. During March 2012, 306 patients completed a travel survey. GIS maps of patients' travel (modes and distances) were produced. Two focus groups (12 clinical and 13 non-clinical staff) were recorded, transcribed, and analysed using a thematic framework approach. The majority (61%) of patient journeys to and from the surgery were made by car or taxi; main reasons cited were 'convenience', 'time saving', and 'no alternative' for accessing the surgery. Using distances calculated via ArcGIS, the annual estimated CO2 equivalent carbon emissions for the practice totalled approximately 63 tonnes. Predominant themes from interviews related to issues with systems for booking appointments and repeat prescriptions; alternative travel modes; delivering health care; and solutions to reducing travel. The modes and distances of patient travel can be accurately determined and allow appropriate carbon emission calculations for GP practices. Although challenging, there is scope for identifying potential solutions (for example, modifying administration systems and promoting walking) to reduce 'avoidable' journeys and cut carbon emissions while maintaining access to health care.

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)

Nonspecific suppressor T cells cause decreased mixed lymphocyte culture reactivity in bone marrow transplant patients

International Nuclear Information System (INIS)

Harada, M.; Ueda, M.; Nakao, S.; Kondo, K.; Odaka, K.; Shiobara, S.; Matsue, K.; Mori, T.; Matsuda, T.

1986-01-01

Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period

Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review

NARCIS (Netherlands)

Vonk, L.A.; de Windt, T.S.; Slaper-Cortenbach, Ineke C.M.; Saris, Daniël B.F.

2015-01-01

The evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies,

Allogeneic stem-cell transplantation in patients with Waldenstrom macroglobulinemia: report from the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation.

NARCIS (Netherlands)

Kyriakou, C.; Canals, C.; Cornelissen, J.J.; Socie, G.; Willemze, R.; Ifrah, N.; Greinix, H.T.; Blaise, D.; Deconinck, E.; Ferrant, A.; Schattenberg, A.V.M.B.; Harousseau, J.L.; Sureda, A.; Schmitz, N.

2010-01-01

PURPOSE: Allogeneic stem-cell transplantation (alloSCT) is a curative therapeutic option for patients with low-grade lymphoid malignancies. Information regarding alloSCT in Waldenstrom macroglobulinemia (WM) is limited. This study presents the long-term outcome of a large series of patients with WM

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

[EFFECTIVENESS COMPARISON OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION BETWEEN BY AUTOLOGOUS AND ALLOGENEIC TENDON GRAFTS COMBINED WITH HOOK PLATE FIXATION FOR TREATING ACROMIOCLAVICULAR JOINT DISLOCATION].

Science.gov (United States)

Yin, Fei; Sun, Zhenzhong; Wei, Xuming; Liu, Xueguang; Zhou, Ming; Zhuang, Yin; Song, Sheng

2016-05-08

To compare the effectiveness of coracoclavicular ligament reconstruction between by using autologous plantaris tendon graft combined with hook plate fixation and allogeneic tendon graft combined with hook plate fixation for treating acromiocavicular joint dislocation. Thirty-three patients with acromioclavicular joint dislocation who accorded with the inclusion criteria between January 2013 and June 2014 were assigned into 2 groups. The patients were treated with autologous plantaris tendon graft combined with hook plate fixation in group A ( n =17), and with allogeneic tendon graft combined with hook plate fixation in group B ( n =16). Thirteen-one patients was followed up more than 12 months (15 in group A and 16 in group B). There was no significant difference in gender, age, cause of injury, sides, time between injury and surgery, and type of dislocation ( P >0.05). The assessments included operation time, hospitalization time, hospitalization expenses, shoulder range of motion, gap of acromioclavicular, Constant-Murley scores, and visual analogue scale (VAS) for pain. The operation time of group A was significantly longer than that of group B, and the hospitalization expense was significantly lower than that of group B ( P 0.05). No redislocation of acromioclavicular joint and rejection reaction occurred during follow-up. At last follow-up, there was no significant difference in shoulder range of motion, Constant-Murley score, and VAS score between 2 groups ( P >0.05). Coracoclavicular ligament reconstruction by autologous plantaris tendon or allogeneic tendon graft combined with hook plate fixation for the treatment of acromioclavicular joint dislocation can achieve good effectiveness. The appropriate treatment should be chosen according to the patient's economic situation.

In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial.

Science.gov (United States)

Adotevi, O; Godet, Y; Galaine, J; Lakkis, Z; Idirene, I; Certoux, J M; Jary, M; Loyon, R; Laheurte, C; Kim, S; Dormoy, A; Pouthier, F; Barisien, C; Fein, F; Tiberghien, P; Pivot, X; Valmary-Degano, S; Ferrand, C; Morel, P; Delabrousse, E; Borg, C

2018-01-01

Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3.10 6 , 8.10 6 and 12.10 6 NK cells/kg) following by a high-dose interleukin-2 (IL-2). Cetuximab was administered intravenously every week for 7 weeks. Nine patients with liver metastases of colorectal or pancreatic cancers were included, three per dose level. Hepatic artery injection was successfully performed in all patients with no report of dose-limiting toxicity. Two patients had febrile aplasia requiring a short-term antibiotherapy. Grade 3/4 anemia and thrombopenia were also observed related to the chemotherapy. Objective clinical responses were documented in 3 patients and among them 2 occurred in patients injected with cell products harboring two KIR ligand mismatches and one in a patient with one KIR ligand mismatch. Immune monitoring revealed that most patients presented an increase but transient of IL-15 and IL-7 cytokines levels one week after chemotherapy. Furthermore, a high expansion of FoxP3 + regulatory T cells and PD-1 + T cells was observed in all patients, related to IL-2 administration. Our results demonstrated that combining allogeneic NK cells transfer via intra-hepatic artery, cetuximab and a high-dose IL-2 is feasible, well tolerated and may result in clinical responses.

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.

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.)

Mixed Waste Focus Area - Waste form initiative

International Nuclear Information System (INIS)

Nakaoka, R.; Waters, R.; Pohl, P.; Roach, J.

1998-01-01

The mission of the US Department of Energy's (DOE) Mixed Waste Focus Area (MWFA) is to provide acceptable technologies that enable implementation of mixed waste treatment systems which are developed in partnership with end-users, stakeholders, tribal governments, and regulators. To accomplish this mission, a technical baseline was established in 1996 and revised in 1997. The technical baseline forms the basis for determining which technology development activities will be supported by the MWFA. The primary attribute of the technical baseline is a set of prioritized technical deficiencies or roadblocks related to implementation of mixed waste treatment systems. The Waste Form Initiative (WFI) was established to address an identified technical deficiency related to waste form performance. The primary goal of the WFI was to ensure that the mixed low-level waste (MLLW) treatment technologies being developed, currently used, or planned for use by DOE would produce final waste forms that meet the waste acceptance criteria (WAC) of the existing and/or planned MLLW disposal facilities. The WFI was limited to an evaluation of the disposal requirements for the radioactive component of MLLW. Disposal requirements for the hazardous component are dictated by the Resource Conservation and Recovery Act (RCRA), and were not addressed. This paper summarizes the technical basis, strategy, and results of the activities performed as part of the WFI

[Allogenic hematopoietic stem cell transplantation with unrelated cord blood: report of three cases from the Chilean cord blood bank].

Science.gov (United States)

Barriga, Francisco; Wietstruck, Angélica; Rojas, Nicolás; Bertin, Pablo; Pizarro, Isabel; Carmona, Amanda; Guilof, Alejandro; Rojas, Iván; Oyarzún, Enrique

2013-08-01

Public cord blood banks are a source of hematopoietic stem cells for patients with hematological diseases who lack a family donor and need allogeneic transplantation. In June 2007 we started a cord blood bank with units donated in three maternity wards in Santiago, Chile. We report the first three transplants done with cord blood units form this bank. Cord blood units were obtained by intrauterine collection at delivery. They were depleted of plasma and red cells and frozen in liquid nitrogen. Tests for total nucleated cells, CD34 cell content, viral serology, bacterial cultures and HLA A, B and DRB1 were done. Six hundred cord blood units were stored by March 2012. Three patients received allogeneic transplant with cord blood from our bank, two with high risk lymphoblastic leukemia and one with severe congenital anemia. They received conditioning regimens according to their disease and usual supportive care for unrelated donor transplantation until full hematopoietic and immune reconstitution was achieved. The three patients had early engraftment of neutrophils and platelets. The child corrected his anemia and the leukemia patients remain in complete remission. The post-transplant course was complicated with Epstein Barr virus, cytomegalovirus and BK virus infection. Two patients are fully functional 24 and 33 months after transplant, the third is still receiving immunosuppression.

Usage of adenovirus expressing thymidine kinase mediated hepatocellular damage for enabling mouse liver repopulation with allogenic or xenogenic hepatocytes.

Directory of Open Access Journals (Sweden)

Daniel Moreno

Full Text Available It has been shown that the liver of immunodeficient mice can be efficiently repopulated with human hepatocytes when subjected to chronic hepatocellular damage. Mice with such chimeric livers represent useful reagents for medical and clinical studies. However all previously reported models of humanized livers are difficult to implement as they involve cross-breeding of immunodeficient mice with mice exhibiting genetic alterations causing sustained hepatic injury. In this paper we attempted to create chimeric livers by inducing persistent hepatocellular damage in immunodeficient Rag2(-/- γc(-/- mice using an adenovirus encoding herpes virus thymidine kinase (AdTk and two consecutive doses of ganciclovir (GCV. We found that this treatment resulted in hepatocellular damage persisting for at least 10 weeks and enabled efficient engraftment and proliferation within the liver of either human or allogenic hepatocytes. Interestingly, while the nodules generated from the transplanted mouse hepatocytes were well vascularized, the human hepatocytes experienced progressive depolarization and exhibited reduced numbers of murine endothelial cells inside the nodules. In conclusion, AdTk/GCV-induced liver damage licenses the liver of immunodeficient mice for allogenic and xenogenic hepatocyte repopulation. This approach represents a simple alternative strategy for chimeric liver generation using immunodeficient mice without additional genetic manipulation of the germ line.

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

Directory of Open Access Journals (Sweden)

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

Pitavastatin demonstrates long-term efficacy, safety and tolerability in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia

DEFF Research Database (Denmark)

Stender, Steen; Budinski, Dragos; Hounslow, Neil

2013-01-01

Aims: To assess the long-term efficacy, safety and tolerability of pitavastatin (2 and 4 mg) in elderly patients (≥65 years of age) with primary hypercholesterolaemia or combined (mixed) dyslipidaemia.Design: Patients (n = 545) who had completed a 12-week double-blind comparative study (core study...... Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) targets for low-density lipoprotein cholesterol (LDL-C) was determined.Results: Of the patients enrolled, 539 received at least one dose of pitavastatin (safety population: men, 45.5%; Caucasian, 99.1%; mean age, 70.3 years; range, 65......-89 years). Only 17% of patients required up-titration to pitavastatin 4 mg. After 60 weeks, NCEP ATP III and EAS targets were attained by 93.8% and 89.0% of patients, respectively. Plasma LDL-C declined by 43.4% and high-density lipoprotein cholesterol increased by 9.6% versus core-study baseline values...

Outcome of allogeneic SCT in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy.

Science.gov (United States)

Oyekunle, Anthony; Zander, Axel R; Binder, Mascha; Ayuk, Francis; Zabelina, Tatjana; Christopeit, Maximilian; Stübig, Thomas; Alchalby, Haefaa; Schafhausen, Philippe; Lellek, Heinrich; Wolschke, Christine; Müller, Ingo; Bacher, Ulrike; Kröger, Nicolaus

2013-04-01

The introduction of tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) led to a dramatic change in the role of allogeneic stem cell transplantation (SCT) with a rapid decline in the number of patients receiving SCT in first chronic phase (CP1). We evaluated 68 consecutive patients in all phases of CML (male/female = 39:29, 27 in CP1), who received SCT from related/unrelated donors (related/unrelated = 23:45) under myeloablative or reduced intensity conditioning (MAC/RIC = 45:23). Forty-eight patients (71 %) received TKIs pre-SCT, 20 patients post-SCT (29 %). Overall survival (OS) of CP1 patients achieved a plateau of 85 % at 10 months. Relapse-free survival (RFS) of CP1 patients was 85 % at 1 and 2 years, and 81 % at 5 years. Multivariate analysis showed adverse OS and RFS for patients transplanted >CP1 (hazard ratio (HR) = 6.61 and 4.62) and those who had grade III-IV aGvHD (HR = 2.45 and 1.82). Patients with advanced CML had estimated OS of 65 and 47 %; and RFS of 41 and 32 % at 1 and 2 years respectively. Therefore, for patients with advanced CML phases, allogeneic SCT provides an acceptable chance of cure. Transplant research should focus on improving conditioning regimens and post-SCT management for this subgroup of CML patients.

3-phase bone imaging and SPECT in the follow up of patients with allogenic vascularized knee joint transplants

International Nuclear Information System (INIS)

Manthey, N.; Tatsch, K.; Hahn, K.; Kirschner, M.H.; Nerlich, A.; Hofmann, G.O.

2001-01-01

Vascularized allotransplantation of knee joints under immunosuppression is a novel approach in orthopedic surgery. During the postoperative course immunosuppressive management depends on perfusion and viability of the graft. Aim: Evaluation of different diagnostic tools in regard to their usefulness and reliability to provide information about microvascularity and viability of vascularized knee joint allografts. Methods: Four patients with allogenic knee joint transplants were studied up to 26 months after transplantation with 3-phase bone scans and SPECT. The results were compared with duplex sonography, angiography, and histology. Results: Two cases without complications were characterized by adequate perfusion in duplex sonography, angiography and early bone scans. Late bone scans demonstrated increased bone metabolism of the transplant. Corresponding biopsy revealed viable bone cells. In one case with partial thrombosis and one case with complete thrombosis of the transplant vessels rapidly decreasing or missing perfusion was detected by duplex sonography, angiography, and bloodpool scintigraphy. Late bone scans showed reduced or absent bone metabolism. Biopsy demonstrated necrotic bone tissue. Due to the advantage of a tomographic technique SPECT allowed a more reliable assessment of graft viability as compared to planar imaging. Conclusion: Our findings confirm bone scintigraphy as a valuable diagnostic tool in patients with allogenic vascularized knee joint transplants. In contrast to other diagnostic approaches, scintigraphy provides reliable information on both viability and perfusion of the transplant within a single non-invasive clinical investigation. (orig.)

3-phase bone imaging and SPECT in the follow up of patients with allogenic vascularized knee joint transplants

Energy Technology Data Exchange (ETDEWEB)

Manthey, N.; Tatsch, K.; Hahn, K. [Dept. of Nuclear Medicine, Klinikum Grosshadern, Ludwig-Maximilians-Univ. of Munich (Germany); Kirschner, M.H. [Dept. of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-Univ. of Munich (Germany); Nerlich, A. [Inst. of Pathology, Klinikum Grosshadern, Ludwig-Maximilians-Univ. of Munich (Germany); Hofmann, G.O. [Trauma Center Murnau (Germany)

2001-12-01

Vascularized allotransplantation of knee joints under immunosuppression is a novel approach in orthopedic surgery. During the postoperative course immunosuppressive management depends on perfusion and viability of the graft. Aim: Evaluation of different diagnostic tools in regard to their usefulness and reliability to provide information about microvascularity and viability of vascularized knee joint allografts. Methods: Four patients with allogenic knee joint transplants were studied up to 26 months after transplantation with 3-phase bone scans and SPECT. The results were compared with duplex sonography, angiography, and histology. Results: Two cases without complications were characterized by adequate perfusion in duplex sonography, angiography and early bone scans. Late bone scans demonstrated increased bone metabolism of the transplant. Corresponding biopsy revealed viable bone cells. In one case with partial thrombosis and one case with complete thrombosis of the transplant vessels rapidly decreasing or missing perfusion was detected by duplex sonography, angiography, and bloodpool scintigraphy. Late bone scans showed reduced or absent bone metabolism. Biopsy demonstrated necrotic bone tissue. Due to the advantage of a tomographic technique SPECT allowed a more reliable assessment of graft viability as compared to planar imaging. Conclusion: Our findings confirm bone scintigraphy as a valuable diagnostic tool in patients with allogenic vascularized knee joint transplants. In contrast to other diagnostic approaches, scintigraphy provides reliable information on both viability and perfusion of the transplant within a single non-invasive clinical investigation. (orig.)

Preoperative embolization in surgical treatment of spinal metastases

DEFF Research Database (Denmark)

Clausen, Caroline; Dahl, Benny; Frevert, Susanne Christiansen

2015-01-01

PURPOSE: To assess whether preoperative transcatheter arterial embolization of spinal metastases reduces blood loss, the need for transfusion with allogeneic red blood cells (RBCs), and surgery time in the surgical treatment of patients with symptomatic metastatic spinal cord compression. MATERIALS......L) versus 902 mL (SD, 416 mL). CONCLUSIONS: Preoperative embolization in patients with symptomatic spinal metastasis independent of primary tumor diagnosis did not reduce intraoperative blood loss and allogeneic RBC transfusion significantly but did reduce the surgery time. A small reduction...... instrumentation and randomly assigned to either preoperative embolization (n = 23) or a control group (n = 22). The primary outcome was intraoperative blood loss. Secondary outcomes were perioperative blood loss, allogeneic RBC transfusion, and surgery time. Analyses were performed by intention-to-treat. RESULTS...

A randomized trial on the effect of a multimodal intervention on physical capacity, functional performance and quality of life in adult patients undergoing allogeneic SCT

DEFF Research Database (Denmark)

Jarden, M; Baadsgaard, M T; Hovgaard, D J

2009-01-01

The aim of this randomized controlled trial was to investigate the effect of a 4- to 6-week multimodal program of exercise, relaxation and psychoeducation on physical capacity, functional performance and quality of life (QOL) in allogeneic hematopoietic cell transplantation (allo-HSCT) adult...

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...

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

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...

T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

International Nuclear Information System (INIS)

Kruisbeek, A.M.; Hathcock, K.S.; Hodes, R.J.; Singer, A.

1982-01-01

In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

Clockwise: A Mixed-Media File System

NARCIS (Netherlands)

Bosch, H.G.P.; Jansen, P.G.; Mullender, Sape J.

This (short) paper presents the Clockwise, a mixed-media file system. The primary goal of the Clockwise is to provide a storage architecture that supports the storage and retrieval of best-effort and real-time file system data. Clockwise provides an abstraction called a dynamic partition that groups

Influences of Gender, Religion, Dietary Patterns, and Mixed-sex Education on Aggressiveness in Children: A Sociodemographic Study in Municipal Primary Schools of South Delhi.

Science.gov (United States)

Jain, Khushbu; Sharma, Schweta; Prajna, Samani Chaitanya; Jain, Viney

2018-01-01

Increasing antisocial and violent behaviors in adolescents and young adults present serious challenges for public health. Children with persistent high levels of aggressiveness are often associated with developing conduct disorders later in life. Early detection of highly aggressive children and sociodemographic risk-modifying factors are important for developing effective preventive strategies. The present study was undertaken to assess levels of aggressiveness for detecting highly aggressive children in sample populations of primary school children in an urban setting and determine significant biosociocultural risk-modifying factors in this scenario. The study was conducted during August-September, 2015 in 5 primary schools of South Delhi Municipal Corporation. Sociodemographic data on 2080 students were collected. Overall aggressiveness scores (OA-Scores) were estimated using a self-report questionnaire in Hindi. Categorizing students according to their OA-Scores, the data revealed that highly aggressive children constituted 4.3% of the study population. Analysis showed significant influence of (a) gender: boys displayed higher levels of aggressiveness compared to girls; (b) dietary pattern: omnivores showed higher aggressiveness than vegetarians; and (c) school environment: boys in mixed-sex (coeducational) schools displayed lower aggressiveness than from single-sex schools. Statistically significant influences of religion (Hindu/Muslim) and family type (joint/nuclear) on aggressiveness profiles were not noticeable. Vegetarian diets and mixed-sex education act as protective factors in the development of aggressiveness in children, especially among boys. Extending investigations to populations differing in geography and cultural backgrounds are warranted to verify present results.

How Does Influenza A (H1N1 Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

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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.

Validation of Computational Fluid Dynamics Calculation Using Rossendorf Coolant Mixing Model Flow Measurements in Primary Loop of Coolant in a Pressurized Water Reactor Model

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Istvan Farkas

2016-08-01

Full Text Available The aim of this work is to simulate the thermohydraulic consequences of a main steam line break and to compare the obtained results with Rossendorf Coolant Mixing Model (ROCOM 1.1 experimental results. The objective is to utilize data from steady-state mixing experiments and computational fluid dynamics (CFD calculations to determine the flow distribution and the effect of thermal mixing phenomena in the primary loops for the improvement of normal operation conditions and structural integrity assessment of pressurized water reactors. The numerical model of ROCOM was developed using the FLUENT code. The positions of the inlet and outlet boundary conditions and the distribution of detailed velocity/turbulence parameters were determined by preliminary calculations. The temperature fields of transient calculation were averaged in time and compared with time-averaged experimental data. The perforated barrel under the core inlet homogenizes the flow, and therefore, a uniform temperature distribution is formed in the pressure vessel bottom. The calculated and measured values of lowest temperature were equal. The inlet temperature is an essential parameter for safety assessment. The calculation predicts precisely the experimental results at the core inlet central region. CFD results showed a good agreement (both qualitatively and quantitatively with experimental results.

Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic Heart Failure

DEFF Research Database (Denmark)

Kastrup, Jens; Schou, Morten; Gustafsson, Ida

2017-01-01

BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose-derived stromal cell (CSCC_ASC) product from healthy donors. It is produced without animal products, in closed bioreactor systems...

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.

Proteolytically modified human beta 2-microglobulin augments the specific cytotoxic activity in murine mixed lymphocyte culture

DEFF Research Database (Denmark)

Nissen, Mogens Holst; Claësson, M H

1987-01-01

the endogenous production of interleukin 2 in the MLC culture; monoclonal antibody which reacts with both the native beta 2-m and M-beta 2-m molecule blocks the augmentation of cytotoxic T lymphocyte production induced by M-beta 2-m; murine as well as human MLC responder cells can proteolytically modify native......A proteolytically modified form of beta 2-microglobulin (beta 2-m) present in the serum of patients suffering from autoimmune, immunodeficient diseases and cancer has been reported in the literature. In the present study we show that human beta 2-m as well as the proteolytically modified human form...... (M-beta 2-m) bind to murine lymphocytes expressing H-2 class I antigens; M-beta 2-m, when added at day 0 and 1 of culture in nanomolar concentrations to a one-way murine allogeneic mixed lymphocyte culture (MLC) augments the generation of specific cytotoxic T lymphocytes; M-beta 2-m increases...

EXPERIENCE OF USING ALLOGENIC BIOIMPLANTS IN LARYNGEAL RESECTION

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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.

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia.

Science.gov (United States)

Wang, Jingbo; Yuan, Lei; Cheng, Haoyu; Fei, Xinhong; Yin, Yumin; Gu, Jiangying; Xue, Song; He, Junbao; Yang, Fan; Wang, Xiaocan; Yang, Yixin; Zhang, Weijie

2018-01-09

There is an ongoing debate concerning the performance of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) in pediatric patients with acute refractory leukemia, in whom the prognosis is quite dismal. Few studies have ever been conducted on this subject. This may be partly due to missed opportunities by majority of the patients in such situations. To investigate the feasibility, evaluate the efficiency, and identify the prognostic factors of allo-HSCT in this sub-setting, the authors performed a single institution-based retrospective analysis. A total of 44 patients, of whom 28 had acute myeloid leukemia (AML), 13 had acute lymphocytic leukemia (ALL), and 3 had mixed phenotype leukemia (MPL), were enrolled in this study. With a median follow-up of 19 months, the estimated 2-year overall survival (OS) and progression free survival (PFS) were 34.3% (95% CI, 17.9-51.4%) and 33.6% (95% CI, 18.0-50.1%), respectively. The estimated 2-year incidence rates of relapse and non-relapse mortality (NRM) were 43.8% (95% CI 26.4-60.0%) and 19.6% (95% CI 9.1-32.9%), respectively. The estimated 100-day cumulative incidence of acute graft versus host disease (aGvHD) was 43.6% (95% CI 28.7-57.5%), and the 1-year cumulative incidence of chronic GvHD (cGvHD) was 45.5% (95% CI 30.5-59.3%). Compared with the previous studies, the multivariate analysis in this study additionally identified that female donors and cGvHD were associated with lower relapse and better PFS and OS. Male recipients, age younger than 10 years, a diagnosis of ALL, and the intermediate-adverse cytogenetic risk group were associated with increased relapse. On the contrary, extramedullary disease (EMD) and aGvHD were only linked to worse PFS. These data suggested that although only one-third of the patients would obtain PFS over 2 years, salvaged allo-HSCT is still the most reliable and best therapeutic strategy for refractory pediatric acute leukemia. If probable, choosing a female donor, better

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

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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

Astrovirus infection in hospitalized infants with severe combined immunodeficiency after allogeneic hematopoietic stem cell transplantation.

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Werner Wunderli

Full Text Available Infants with severe primary combined immunodeficiency (SCID and children post-allogeneic hematopoietic stem cell transplantation (HSCT are extremely susceptible to unusual infections. The lack of generic tools to detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge to clinicians and virologists. We investigated retrospectively the causes of a fatal disseminated viral infection with meningoencephalitis in an infant with gamma C-SCID and of chronic gastroenteritis in 2 other infants admitted for HSCT during the same time period. Analysis was undertaken by combining cell culture, electron microscopy and sequence-independent single primer amplification (SISPA techniques. Caco-2 cells inoculated with fecal samples developed a cytopathic effect and non-enveloped viral particles in infected cells were detected by electron microscopy. SISPA led to the identification of astrovirus as the pathogen. Both sequencing of the capsid gene and the pattern of infection suggested nosocomial transmission from a chronically excreting index case to 2 other patients leading to fatal infection in 1 and to transient disease in the others. Virus-specific, real-time reverse transcription polymerase chain reaction was then performed on different stored samples to assess the extent of infection. Infection was associated with viremia in 2 cases and contributed to death in 1. At autopsy, viral RNA was detected in the brain and different other organs, while immunochemistry confirmed infection of gastrointestinal tissues. This report illustrates the usefulness of the combined use of classical virology procedures and modern molecular tools for the diagnosis of unexpected infections. It illustrates that astrovirus has the potential to cause severe disseminated lethal infection in highly immunocompromised pediatric patients.

Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis.

Science.gov (United States)

Schetelig, Johannes; van Biezen, Anja; Brand, Ronald; Caballero, Dolores; Martino, Rodrigo; Itala, Maija; García-Marco, José A; Volin, Liisa; Schmitz, Norbert; Schwerdtfeger, Rainer; Ganser, Arnold; Onida, Francesco; Mohr, Brigitte; Stilgenbauer, Stephan; Bornhäuser, Martin; de Witte, Theo; Dreger, Peter

2008-11-01

Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p-) have a poor prognosis. Although allogeneic hematopoietic stem-cell transplantation (HCT) has the potential to cure patients with advanced CLL, it is not known whether this holds true for patients with 17p-CLL. Baseline data from patients, for whom information on the presence of 17p-CLL was available, were downloaded from the European Group for Blood and Marrow Transplantation database. Additional information on the course of CLL and follow-up was collected with a questionnaire. A total of 44 patients with 17p-CLL received allogeneic HCT between March 1995 and July 2006 from a matched sibling (n = 24) or an alternative donor (n = 20). 17p-CLL had been diagnosed by fluorescent in situ hybridization in 82% of patients and by conventional banding in 18% of patients. The median age was 54 years. Before HCT, a median of three lines of chemotherapy had been administered. At HCT, 53% of patients were in remission. Reduced-intensity conditioning was applied in 89% of patients. Acute, grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19 patients were alive, with a median observation time of 39 months (range, 18 to 101 months). Three-year overall survival and progression-free survival rates were 44% and 37%, respectively. The cumulative incidence of progressive disease at 4 years was 34%. No late relapse occurred in nine patients with a follow-up longer than 4 years. Allogeneic HCT has the potential to induce long-term disease-free survival in patients with 17p-CLL.

Application of MultiStem® allogeneic cells for immunomodulatory therapy: clinical progress and pre-clinical challenges in prophylaxis for graft vs host disease

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Bart eVaes

2012-11-01

Full Text Available The last decade has seen much progress in adjunctive cell therapy for immune disorders. Both corporate and institutional Phase III studies have been run using mesenchymal stromal cells (MSC for treatment of Graft vs Host Disease (GvHD, and product approval has been achieved for treatment of pediatric GvHD in Canada and New Zealand (Prochymal®; Osiris Therapeutics. This effectiveness has prompted the prophylactic use of adherent stem cells at the time of allogeneic hematopoietic stem cell transplantation (HSCT to prevent occurrence of GvHD and possibly provide stromal support for hematopoietic recovery. The MultiStem® product is an adult adherent stem cell product derived from bone marrow which has significant clinical exposure. MultiStem cells are currently in phase II clinical studies for treatment of ischemic stroke and ulcerative colitis, with Phase I studies completed in acute myocardial infarction and for GvHD prophylaxis in allogeneic HSCT, demonstrating that MultiStem administration was well tolerated while the incidence and severity of GvHD was reduced. In advancing this clinical approach, it is important to recognize that alternate models exist based on clinical manufacturing strategies. Corporate sponsors exploit the universal donor properties of adherent stem cells and manufacture at large scale, with many products obtained from one or limited donors and used across many patients. In Europe, institutional sponsors often produce allogeneic product in a patient designated context. For this approach, disposable bioreactors producing <10 products per donor in a closed system manner are very well suited. In this review, the use of adherent stem cells for GvHD prophylaxis is summarized and the suitability of disposable bioreactors for MultiStem production is presented, with an emphasis on quality control parameters, which are critical with a multiple donor approach for manufacturing.

Anoxic and oxic phototrophic primary production during the Precambrian

DEFF Research Database (Denmark)

Ebey-Honeycutt, Christina Marie; Bjerrum, Christian J.; Canfield, Donald Eugene

2009-01-01

of the mixed layer often lies above the base of the photic zone . Thus, an ecosystem model for the Precambrian should reflect the net primary production (NPP) of oxygenic phototrophs in the mixed layer and anoxygenic phototrophs below (NPPox and NPPred, respectively). Satelite data and a vertically generalized...

Influence of stimulated Raman scattering on the conversion efficiency in four wave mixing

International Nuclear Information System (INIS)

Wunderlich, R.; Moore, M.A.; Garrett, W.R.; Payne, M.G.

1988-01-01

Secondary nonlinear optical effects following parametric four wave mixing in sodium vapor are investigated. The generated ultraviolet radiation induces stimulated Raman scattering and other four wave mixing process. Population transfer due to Raman transitions strongly influences the phase matching conditions for the primary mixing process. Pulse shortening and a reduction in conversion efficiency are observed. 8 refs., 3 figs

Establishing an autologous versus allogeneic hematopoietic cell transplant program in nations with emerging economies.

Science.gov (United States)

Chaudhri, Naeem A; Aljurf, Mahmoud; Almohareb, Fahad I; Alzahrani, Hazzaa A; Bashir, Qaiser; Savani, Bipin; Gupta, Vikas; Hashmi, Shahrukh K

2017-12-01

More than 70,000 hematopoietic cell transplants are currently performed each year, and these continue to increase every year. However, there is a significant variation in the number of absolute transplants and transplant rates between centers, countries, and global regions. The prospect for emerging countries to develop a hematopoietic cell transplantation (HCT) program, as well as to decide on whether autologous HCT (auto-HCT) or allogeneic HCT (allo-HCT) should be established to start with, relies heavily on factors that can explain differences between these two procedures. Major factors that will influence a decision about establishing the type of HCT program are macroeconomic factors such as organization of the healthcare network, available resources and infrastructure. Prevalence of specific diseases in the region as well genetic background of donors and recipients will also influence the mandate or priority of the HCT in the national healthcare plan to explain some of the country-specific differences. Furthermore, microeconomic factors play a role, such as center-specific experience in treating various disorders requiring hematopoietic stem cell transplantation, along with accreditation status and patient volume. The objective of the transplant procedure was to improve the survival and quality of life of patients. The regional difference that one notices in emerging countries about the higher number of allo-HCT compared with auto-HCT procedures performed is primarily based on suboptimal healthcare network in treating various malignant disorders that are the primary indication for auto-stem cell transplantation. In this context, nonmalignant disorders such as bone marrow failure syndromes, inherited genetic disorders and hemoglobinopathies have become the major indication for stem cell transplantation. Better understanding of these factors will assist in establishing new transplant centers in the emerging countries to achieve their specific objectives and

Bacterial infections associated with allogenic bone transplantation

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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.

Feasibility and Efficiency of Human Bone Marrow Stromal Cell Culture with Allogeneic Platelet Lysate-Supplementation for Cell Therapy against Stroke

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Chengbo Tan

2016-01-01

Full Text Available Currently, there is increasing interest in human bone marrow stromal cells (hBMSCs as regeneration therapy against cerebral stroke. The aim of the present study was to evaluate the feasibility and validity of hBMSC cultures with allogeneic platelet lysates (PLs. Platelet concentrates (PC were harvested from healthy volunteers and made into single donor-derived PL (sPL. The PL mixtures (mPL were made from three different sPL. Some growth factors and platelet cell surface antigens were detected by enzyme-linked immunosorbent assay (ELISA. The hBMSCs cultured with 10% PL were analyzed for their proliferative potential, surface markers, and karyotypes. The cells were incubated with superparamagnetic iron oxide (SPIO agents and injected into a pig brain. MRI and histological analysis were performed. Consequently, nine lots of sPL and three mPL were prepared. ELISA analysis showed that PL contained adequate growth factors and a particle of platelet surface antigens. Cell proliferation capacity of PLs was equivalent to or higher than that of fetal calf serum (FCS. No contradiction in cell surface markers and no chromosomal aberrations were found. The MRI detected the distribution of SPIO-labeled hBMSCs in the pig brain. In summary, the hBMSCs cultured with allogeneic PL are suitable for cell therapy against stroke.

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

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.

Mixed ligand chelates of rare earths in aqueous solution

International Nuclear Information System (INIS)

Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

1981-01-01

Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

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.

Development of a tissue-engineered human oral mucosa equivalent based on an acellular allogeneic dermal matrix: a preliminary report of clinical application to burn wounds.

Science.gov (United States)

Iida, Takuya; Takami, Yoshihiro; Yamaguchi, Ryo; Shimazaki, Shuji; Harii, Kiyonori

2005-01-01

Tissue-engineered skin equivalents composed of epidermal and dermal components have been widely investigated for coverage of full-thickness skin defects. We developed a tissue-engineered oral mucosa equivalent based on an acellular allogeneic dermal matrix and investigated its characteristics. We also tried and assessed its preliminary clinical application. Human oral mucosal keratinocytes were separated from a piece of oral mucosa and cultured in a chemically-defined medium. The keratinocytes were seeded on to the acellular allogeneic dermal matrix and cultured. Histologically, the mucosa equivalent had a well-stratified epithelial layer. Immunohistochemical study showed that it was similar to normal oral mucosa. We applied this equivalent in one case with an extensive burn wound. The equivalent was transplanted three weeks after the harvest of the patient's oral mucosa and about 30% of the graft finally survived. We conclude that this new oral mucosa equivalent could become a therapeutic option for the treatment of extensive burns.

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.

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

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Cahu, X; Labopin, M; Giebel, S

2016-01-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a therapeutic option for adult patients with T-cell ALL (T-ALL). Meanwhile, few allo-SCT data specific to adult T-ALL have been described thus far. Specifically, the optimal myeloablative conditioning regimen is unknown...... patients with T-ALL entitled to receive a myeloablative allo-SCT may benefit from TBI-based regimens.Bone Marrow Transplantation advance online publication, 30 November 2015; doi:10.1038/bmt.2015.278....

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 ...

The effect of iron-deficiency anemia on cytolytic activity of mice spleen and peritoneal cells against allogenic tumor cells

International Nuclear Information System (INIS)

Kuvibidila, S.R.; Baliga, B.S.; Suskind, R.M.

1983-01-01

The capacity of spleen and peritoneal cells from iron deficient mice, ad libitum fed control mice, and pair-fed mice to kill allogenic tumor cells (mastocytoma tumor P815) has been investigated. In the first study, mice were sensitized in vivo with 10(7) viable tumor cells 51 and 56 days after weaning. The capacity of splenic cells and peritoneal cells from sensitized and nonsensitized mice to kill tumor cells was evaluated 5 days after the second dose of tumor cells. At ratios of 2.5:1 to 100:1 of attacker to target cells, the percentage 51 Cr release after 4 h of incubation was significantly less in iron-deficient mice than control and/or pair-fed mice (p less than 0.05). Protein-energy undernutrition in pair-fed mice had no significant effect. In the second study, spleen cells and enriched T cell fractions were incubated in vitro for 5 days with uv irradiated Balb/C spleen cells in a 2:1 ratio. The cytotoxic capacity against the same allogenic tumor cells was again evaluated. The percentage chromium release at different attacker to target cells was less than 30% in the iron-deficient group compared to either control or pair-fed supporting the results of in vivo sensitized cells. The possible mode of impairment of the cytotoxic capacity is discussed

Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT)

International Nuclear Information System (INIS)

Gerstein, Johanna; Meyer, Andreas; Fruehauf, Joerg; Karstens, Johann H.; Bremer, Michael; Sykora, Karl-Walter

2009-01-01

Purpose: to retrospectively assess the incidence and time course of renal dysfunction in children (≤ 16 years) following total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT). Patients and methods: between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCt. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. Results: twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCt was 97.3%. Conclusion: the incidence of persistent renal dysfunction after fractionated TBI with total doses ≤ 12 Gy was very low in this analysis. (orig.)

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...

Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell--depleted SCT

NARCIS (Netherlands)

van Esser, J W; van der Holt, B; Meijer, E; Niesters, H G; Trenschel, R; Thijsen, S F; van Loon, A M; Frassoni, F; Bacigalupo, A; Schaefer, U W; Osterhaus, A D; Gratama, J W; Löwenberg, B; Verdonck, L F; Cornelissen, J J

2001-01-01

Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and

Predominant or complete recipient T-cell chimerism following alemtuzumab-based allogeneic transplantation is reversed by donor lymphocytes and not associated with graft failure.

Science.gov (United States)

Mohamedbhai, Sajir G; Edwards, Noha; Morris, Emma C; Mackinnon, Stephen; Thomson, Kirsty J; Peggs, Karl S

2012-02-01

The clinical significance of mixed chimerism following allogeneic haematopoietic stem cell transplantation (HSCT) remains controversial. Its relevance and incidence are probably influenced by the conditioning regimen and incorporation of T-cell depletion. The presence of recipient chimerism levels >40-50% following T-cell replete reduced intensity transplantation correlates with a high risk of graft rejection, regardless of donor-lymphocyte infusions, but it is unclear whether this finding translates to T-cell depleted transplants. We conducted a retrospective single-institution analysis of patients receiving alemtuzumab-based HSCT. 27/152 (18%) evaluable cases had predominantly recipient T-cell chimerism at 3 months or beyond. By contrast, coincident chimerism in the granulocyte lineage was predominantly of donor origin (median 100%) in all but one patient. Donor lymphocyte infusion effectively converted predominantly recipient T-cell chimerism to ful donor chimerism in all evaluable cases including three cases with no detectable donor T cells. The only graft failure occurred in the patient with predominantly recipient myeloid chimerism in whom rejection occurred rapidly before donor lymphocytes could be administered. We conclude that predominant or complete recipient T-cell chimerism following alemtuzumab-based regimens does not have the same clinical implications as that following T-cell replete transplants and can be effectively converted with donor lymphocytes without the need for lympho-depleting agents or re-conditioning. © 2011 Blackwell Publishing Ltd.

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

The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Mortensen, Katrine Brandt; Gerds, Thomas Alexander; Bjerrum, Ole Weis

2014-01-01

The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed...... no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect...

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

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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.

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

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...

Regulation of primary cytotoxic T lymphocyte responses generated during mixed leukocyte culture with H-2d identical Qa-1-disparate cells

International Nuclear Information System (INIS)

Huston, D.P.; Tavana, G.; Rich, R.R.; Gressens, S.E.

1986-01-01

Cytotoxic lymphocyte (CTL) responses are not usually generated during primary mixed leukocyte culture (MLC) with H-2 identical cells. Thus NZB mice are unusual in that their spleen cells do mount CTL responses during primary MLC with H-2d identical stimulator cells; the predominant target antigen for these NZB responses is Qa-1b. Considering the numerous immunoregulatory defects in NZB mice, we postulated that these NZB anti-Qa-1 primary CTL responses were due to an abnormality in T suppressor cell activity. Cellular interactions capable of suppressing NZB anti-Qa-1 primary CTL responses were investigated by using one-way and two-way MLC with spleen cells from NZB mice and other H-2d strains. Although H-2d identical one-way MLC with the use of NZB responders resulted in substantial CTL responses, only minimal CTL responses were detected from two-way MLC with the use of NZB spleen cells plus nonirradiated spleen cells from other H-2d mice. Thus the presence of non-NZB spleen cells in the two-way H-2d identical MLC prevented the generation of NZB CTL. Noncytotoxic mechanisms were implicated in the suppression of the NZB CTL responses during two-way MLC, because only minimal CTL activity was generated when NZB spleen cells were cultured with semiallogeneic, H-2d identical (e.g., NZB X BALB) F1 spleen cells. The observed suppression could be abrogated with as little as 100 rad gamma-irradiation to the non-NZB spleen cells. The phenotype of these highly radiosensitive spleen cells was Thy-1+, Lyt-1+, Lyt-2-, L3T4+. The functional presence of these cells in the spleens of semiallogeneic, H-2d identical F1 mice indicated that their deficiency in NZB mice was a recessive trait. These data suggest that NZB mice lack an L3T4+ cell present in the spleens of normal mice that is capable of suppressing primary anti-Qa-1 CTL responses

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

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Tanujan Thangarajah

Full Text Available Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds.In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5, or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5 were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery.Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047, 9 (P = 0.028, and 12 weeks (P = 0.009. In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015, and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039. No failures of tendon-bone healing were noted in either group.Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

NARCIS (Netherlands)

Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

2014-01-01

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and

Mixed ice accretion on aircraft wings

Science.gov (United States)

Janjua, Zaid A.; Turnbull, Barbara; Hibberd, Stephen; Choi, Kwing-So

2018-02-01

Ice accretion is a problematic natural phenomenon that affects a wide range of engineering applications including power cables, radio masts, and wind turbines. Accretion on aircraft wings occurs when supercooled water droplets freeze instantaneously on impact to form rime ice or runback as water along the wing to form glaze ice. Most models to date have ignored the accretion of mixed ice, which is a combination of rime and glaze. A parameter we term the "freezing fraction" is defined as the fraction of a supercooled droplet that freezes on impact with the top surface of the accretion ice to explore the concept of mixed ice accretion. Additionally we consider different "packing densities" of rime ice, mimicking the different bulk rime densities observed in nature. Ice accretion is considered in four stages: rime, primary mixed, secondary mixed, and glaze ice. Predictions match with existing models and experimental data in the limiting rime and glaze cases. The mixed ice formulation however provides additional insight into the composition of the overall ice structure, which ultimately influences adhesion and ice thickness, and shows that for similar atmospheric parameter ranges, this simple mixed ice description leads to very different accretion rates. A simple one-dimensional energy balance was solved to show how this freezing fraction parameter increases with decrease in atmospheric temperature, with lower freezing fraction promoting glaze ice accretion.

Immunological tolerance induced by galectin-1 in rat allogeneic renal transplantation.

Science.gov (United States)

Xu, Gaosi; Tu, Weiping; Xu, Chengyun

2010-06-01

The existed literatures indicated that galectin-1 has anti-inflammatory effects and plays a pivotal role in autoimmune diseases. Present study was to identify the roles of galectin-1 in acute animal renal allograft rejection. Rat acute rejection models were erected by allogeneic renal transplantation. Galectin-1 injection was performed in different concentrations in renal recipients post-transplantation. Recipient survivals, CD8+ T cell proliferation, production of IFN-gamma, levels of serum CD30, enzyme-linked immunoabsorbent spot assay (ELISPOT) and immunohistochemistry were observed or tested 7days after renal transplantation. Galectin-1 injection can prolong the recipient animal survival, reduce the serum levels of IFN-gamma, soluble CD30, percentage of CD8+ T cell subset, CD8+ T cell-mediated cytotoxicity, and IFN-gamma ELISPOT frequency for allograft recipients. The therapeutic effects of galectin-1 injection on recipient rats were dose-dependent. Galectin-1 plays an important role in CD8+ T cell-mediated renal rejection by inducing immunological tolerance. Copyright 2010 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2016-04-01

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 successfully handled without using the standard therapy to treat anemia with hemotransfusions. Such a case of severe anemia condition resulted after the patient was submitted to ascending aortic aneurism repair, valvar aortic replacement, reimplantation of right coronary ostium, followed by a coronary artery bypass grafting and several postoperative complications. The main clinical and surgical strategies used in this case to avoid blood transfusions were acute normovolemic hemodilution, intraoperative blood cell salvage, and meticulous hemostasis, beyond epsilon-aminocaproic acid, desmopressin, prothrombin complex concentrate, human fibrinogen concentrate, factor VIIa recombinant, erythropoietin and hyperoxic ventilation.

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

REDUCCIÓN DE TRANSFUSIONES ALOGÉNICAS EN CIRUGÍA CARDÍACA EMPLEANDO UN PROGRAMA DE AHORRO DE SANGRE / The reduction of allogeneic blood transfusions in cardiac surgery using a blood saving program

Directory of Open Access Journals (Sweden)

Altinay Padrón Bulit

2009-09-01

Full Text Available Antecedents and objectives: Cardiac surgery has been a process which traditionally requires large amounts of homologous blood transfusions. Due to the negative effects on perioperativemorbimortality, and its cost, some alternatives have been developed in order to reduce or avoid giving a transfusion to the patients. The aim of this study is to put into practice and assess theeffectiveness of a strategy for reducing the use of allogeneic transfusions in the cardiac surgery perioperative at the Ernesto Che Guevara Cardiology Hospital. Method: 151 patients, who were operated on with or without extracorporeal circulation, and who were inserted in a blood saving program that included acute intentional normovolemic hemodilution with autotransfusion during theyear 2008, were studied in order to assess the effectiveness of such strategies. Results: It was possible to avoid the transfusions with allogeneic components in 55 percent of the patients (56.0 percent from the group intervened with extracorporeal circulation (ECC, and 52.64 percent of the patients operated on without ECC and the patients who received the transfusions needed a smaller amount of allogeneic blood components, as well as fewer units administered through the transfusion. Conclusions: The strategies for saving blood were effective in order to reduce the homologous transfusions in the cardiac surgery perioperative.

Implementing online consultations in primary care: a mixed-method evaluation extending normalisation process theory through service co-production.

Science.gov (United States)

Farr, Michelle; Banks, Jonathan; Edwards, Hannah B; Northstone, Kate; Bernard, Elly; Salisbury, Chris; Horwood, Jeremy

2018-03-19

To examine patient and staff views, experiences and acceptability of a UK primary care online consultation system and ask how the system and its implementation may be improved. Mixed-method evaluation of a primary care e-consultation system. Primary care practices in South West England. Qualitative interviews with 23 practice staff in six practices. Patient survey data for 756 e-consultations from 36 practices, with free-text survey comments from 512 patients, were analysed thematically. Anonymised patients' records were abstracted for 485 e-consultations from eight practices, including consultation types and outcomes. Descriptive statistics were used to analyse quantitative data. Analysis of implementation and the usage of the e-consultation system were informed by: (1) normalisation process theory, (2) a framework that illustrates how e-consultations were co-produced and (3) patients' and staff touchpoints. We found different expectations between patients and staff on how to use e-consultations 'appropriately'. While some patients used the system to try and save time for themselves and their general practitioners (GPs), some used e-consultations when they could not get a timely face-to-face appointment. Most e-consultations resulted in either follow-on phone (32%) or face-to-face appointments (38%) and GPs felt that this duplicated their workload. Patient satisfaction of the system was high, but a minority were dissatisfied with practice communication about their e-consultation. Where both patients and staff interact with technology, it is in effect 'co-implemented'. How patients used e-consultations impacted on practice staff's experiences and appraisal of the system. Overall, the e-consultation system studied could improve access for some patients, but in its current form, it was not perceived by practices as creating sufficient efficiencies to warrant financial investment. We illustrate how this e-consultation system and its implementation can be improved

Rethinking workforce boundaries: roles, responsibilities and skill mix and readiness for change in general practice

OpenAIRE

Topping, Annie; Nkosana Nyawata, Idah; Stephenson, John; Featherstone, Valerie A.

2012-01-01

Title: Rethinking workforce boundaries: roles, responsibilities and skill mix and readiness for change in general practice \\ud The Problem \\ud The last 10 years has seen major changes in the way services are delivered in primary care. Skill mix, has offered many practices real opportunities for doing things differently. As the introduction of advanced nurse practitioners (ANPs) and health care assistants (HCAs) into the primary care workforce demonstrate. While workforce redesign has its crit...