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Sample records for allogeneic hematopoietic sct

  1. Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials.

    Science.gov (United States)

    Schrauder, A; von Stackelberg, A; Schrappe, M; Cornish, J; Peters, Christina

    2008-06-01

    The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL-SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatment-related mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL. PMID:18545248

  2. New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT.

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    Chang, X; Zang, X; Xia, C-Q

    2016-03-01

    DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD. PMID:26595077

  3. Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: initial experience from a single center in India.

    Science.gov (United States)

    Kumar, R; Naithani, R; Mishra, P; Mahapatra, M; Seth, T; Dolai, T K; Bhargava, R; Saxena, R

    2009-01-01

    In developing countries, it is important to ascertain the safety of performing allogeneic hematopoietic SCT (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters. We present our experience of performing 40 such transplants from July 2004 to November 2007. Source of stem cells was peripheral blood in 33, bone marrow in six and combined in one. G-CSF started from day +1. The indications were SAA-18, CML-7, AML-7, ALL-2, myelodysplastic syndrome-2 and thalassemia major-4. The median age was 19 years (range 2.2-46) with 29 male and 11 female participants. Antibacterial and antifungal prophylaxis was administered along with conditioning, and at the onset of fever, systemic antibiotics were started. Antifungal agents were added if fever persisted for 3 days. Median time for neutrophil engraftment was 10 days (range 8-17). Fever occurred in 38 (95%) for a median of 5 days (range 1-38), and blood cultures were positive in seven (17.5%). Systemic antibiotics were used in 95% and antifungals in 57.5% cases. The 30-day mortality was nil, and 100-day mortality was 1 (2.5%). After day 100, there were eight fatalities (20%) due to chronic GVHD-3, relapse-2, graft rejection-2, disseminated tuberculosis and aspergillosis-1. Our experience suggests that allogeneic HSCT can be safely performed in non-HEPA filter rooms in India. PMID:18794872

  4. High incidence of oral squamous cell carcinoma independent of HPV infection after allogeneic hematopoietic SCT in Taiwan.

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    Chen, M H; Chang, P M; Li, W Y; Hsiao, L T; Hong, Y C; Liu, C Y; Gau, J P; Liu, J H; Chen, P M; Chiou, T J; Tzeng, C H

    2011-04-01

    Hematopoietic SCT (HSCT) is a well-recognized therapeutic procedure to prolong life and cure patients with life-threatening hematological malignancies; however, the risk of developing secondary carcinoma may increase in long-term survivors. The objective of this study was to determine the incidence and risk factors for secondary squamous carcinoma after HSCT. Between 1984 and 2004, 170 allogeneic HSCT recipients aged >15 years, who had survived for >5 years were enrolled. Demographic data and the characteristics of secondary carcinoma were collected and analyzed for the determination of the incidence and risk of developing secondary carcinoma. Eight patients developed secondary carcinoma, including five oral squamous cell carcinomas, one esophageal, one gastric and one ovarian carcinoma, but no cutaneous carcinomas were detected at a median follow-up of 14.1 years (range, 5.1-23.3 years) after HSCT. The accrual 10-year cumulative incidence of secondary carcinoma was 2.89%. In univariate and multivariate analyses, chronic GVHD and age >40 years at the time of HSCT were both significant risk factors independently associated with the development of secondary carcinoma. Thus, the occurrence of secondary carcinoma is one of the late complications in patients undergoing HSCT. Oral squamous cell carcinoma was more common in our patients after HSCT, indicating the need for lifelong surveillance of the oral cavity. Moreover, because of the relatively long latency in developing secondary carcinoma, extended follow-up is required for a thorough understanding of the incidence and characteristics of secondary carcinoma after HSCT. PMID:20622906

  5. 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...... or unrelated donors for adult patients with AML in first CR were analyzed according to the level of center activity. Transplants were performed in 203 European centers between 2001 and 2007. The 2-year probability of leukemia-free survival (LFS) after RIC-HSCT performed in centers with the lowest...

  6. Reduced-intensity conditioned allogeneic SCT in adults with AML.

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    Reshef, R; Porter, D L

    2015-06-01

    AML is currently the most common indication for reduced-intensity conditioned (RIC) allo-SCT. Reduced-intensity regimens allow a potent GVL response to occur with minimized treatment-related toxicity in patients of older age or with comorbidities that preclude the use of myeloablative conditioning. Whether RIC SCT is appropriate for younger and more standard risk patients is not well defined and the field is changing rapidly; a prospective randomized trial of myeloablative vs RIC (BMT-CTN 0901) was recently closed when early results indicated better outcomes for myeloablative regimens. However, detailed results are not available, and all patients in that study were eligible for myeloablative conditioning. RIC transplants will likely remain the standard of care as many patients with AML are not eligible for myeloablative conditioning. Recent publication of mature results from retrospective and prospective cohorts provide contemporary efficacy and toxicity data for these attenuated regimens. In addition, recent studies explore the use of alternative donors, introduce regimens that attempt to reduce toxicity without reducing intensity, and identify predictive factors that pave the way to personalized approaches. These studies paint a picture of the future of RIC transplants. Here we review the current status of RIC allogeneic SCT in AML. PMID:25730186

  7. Endoscopic diagnosis of cytomegalovirus gastritis after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Yasuo; Kakugawa; Masahiro; Kami; Takahisa; Matsuda; Yutaka; Saito; Sung-Won; Kim; Takahiro; Fukuda; Shin-ichiro; Mori; Tadakazu; Shimoda; Ryuji; Tanosaki; Daizo; Saito

    2010-01-01

    AIM:To clarify the endoscopic and clinical findings of cytomegalovirus(CMV) gastritis after allogeneic hematopoietic stem cell transplantation(allo-SCT).METHODS:Between 1999 and 2005,523 patients underwent allo-SCT at our hospital,and 115 of these patients with gastrointestinal symptoms underwent esophagogastroduodenoscopy.RESULTS:CMV gastritis was diagnosed pathologically in seven patients(1.3%) with the other 108 patients serving as controls.Six of the seven patients developed positive CMV antigenemia,and...

  8. Regulatory T cells and immune tolerance after allogeneic hematopoietic stem cell transplantation

    NARCIS (Netherlands)

    M. Bruinsma (Marieke)

    2010-01-01

    textabstractThe story of allogeneic hematopoietic stem cell transplantation (allo-SCT) begins after the atomic bombings of Hiroshima and Nagasaki in 1945. It was observed that fallout radiation caused dose-dependent depression of hematopoiesis 1. Research first focused on how to protect the hematopo

  9. Nonmyeloablative allogeneic hematopoietic stem cell transplantation.

    OpenAIRE

    Baron, Frédéric; Beguin, Yves

    2002-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective treatment for selected hematological malignancies. Its curative potential is largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols (nonmyeloab...

  10. The Biology of Allogeneic Hematopoietic Cell Resistance

    Science.gov (United States)

    Shizuru, Judith A.; Bhattacharya, Deepta; Cavazzana-Calvo, Marina

    2016-01-01

    At the most basic level, success of an allogeneic hematopoietic cell transplantation (HCT) procedure relies upon the engraftment of recipients with donor hematopoietic stem cells (HSCs) that will generate blood formation for the life of that individual. The formula to achieve durable HSC engraftment involves multiple factors including the recipient conditioning regimen, the nature of the genetic disparity between donor and recipient, and the content of the hematopoietic graft. Animal and clinical studies have shown that the biology of host resistance is complex, involving both immune and nonimmune elements. In this article, we review the factors that contribute to host resistance, describe emerging concepts on the basic biology of resistance, and discuss hematopoietic resistance as it relates specifically to patients with severe combined immunodeficiencies (SCID)— disorders that bring unique insights into the dynamics of cell replacement by allogeneic HSCs and progenitor cells. PMID:19913629

  11. Hepatic complications of allogeneic hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Ramazan Idilman

    2008-09-01

    Full Text Available Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, and acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later post-transplant periods. The aims of the present review are 1 to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order in which they occur, 2 to characterize the diagnostic procedures used to identify them, and finally 3 to present the current therapeutic approaches used to manage these problems.

  12. Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML.

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    Anthias, C; Dignan, F L; Morilla, R; Morilla, A; Ethell, M E; Potter, M N; Shaw, B E

    2014-05-01

    The presence of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) has been associated with adverse outcomes in AML patients treated with chemotherapy alone, but its impact in the setting of allogeneic hematopoietic SCT (HSCT) is less clear. We studied 88 patients who underwent myeloablative (MA) or reduced-intensity conditioned allogeneic HSCT for AML in first or subsequent remission at our center. MRD status was determined using three-color MFC on pre-HSCT BM aspirates, and patients were stratified by MRD status into MRD-negative, low-level MRD-positive (<1%) or high-level MRD-positive groups (1-4.9%). Two-year survival estimates in these groups were 66.8%, 51% and 30%, respectively (P=0.012), and 2-year estimates of relapse were 7.6, 37 and 70% (P<0.001). Pre-HSCT MRD was related to disease characteristics including secondary AML (P=0.002) and primary induction failure (P=0.005), but, despite these strong correlations, MRD remained independently associated with poorer survival in multivariate analysis (hazard ratio, 1.92; P=0.014). Pre-HSCT MRD is associated with adverse clinical outcomes in AML patients undergoing reduced-intensity or MA HSCT in first or subsequent remission and should be integrated into transplant strategies for patients with AML. PMID:24510069

  13. Infections with the 2009 H1N1 influenza virus among hematopoietic SCT recipients: a single center experience.

    Science.gov (United States)

    Rihani, R; Hayajneh, W; Sultan, I; Ghatasheh, L; Abdel-Rahman, F; Hussein, N; Hussein, A; Al-Zaben, A; Sarhan, M; Saad, M

    2011-11-01

    We retrospectively reviewed medical records of 39 hematopoietic SCT (HSCT) recipients who presented at our hospital between 1 October 2009 and 31 January 2010 with the 2009 H1N1 influenza infection. The median age at presentation was 13.8 years (range: 3.3-56.9), infections developed at a median of 585 days (range: 0-2316) post transplant, the majority (n=27, 69%) occurred in allogeneic HSCT recipients, 12 (31%) patients were on immunosuppressive therapy and 12 (31%) had GVHD. Lower airway disease was present in 8 patients (21%). In total, 15 patients (39%) were hospitalized with a median duration of 4.5 days (range: 3-27 days) and 3 (8%) required mechanical ventilation; 2 of whom died. PMID:21243021

  14. Toll-like receptor polymorphisms in allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian; Enevold, Christian; Wang, Tao; Spellman, Stephen; Haagenson, Mike; Lee, Stephanie J; Müller, Klaus

    2014-01-01

    To assess the impact of the genetic variation in toll-like receptors (TLRs) on outcome after allogeneic myeloablative conditioning hematopoietic cell transplantation (HCT), we investigated 29 single nucleotide polymorphisms across 10 TLRs in 816 patients and donors. Only donor genotype of TLR8 rs...... of TLR8 rs3764879 of the donor is associated with outcome after myeloablative conditioned allogeneic HCT....

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

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    Gerstein, Johanna; Meyer, Andreas; Fruehauf, Joerg; Karstens, Johann H.; Bremer, Michael [Dept. of Radiation Oncology, Medical School Hannover (Germany); Sykora, Karl-Walter [Dept. of Pediatric Hematology and Oncology, Medical School Hannover (Germany)

    2009-11-15

    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.)

  16. 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...

  17. Clofarabine Combined with Busulfan Provides Excellent Disease Control in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Kebriaei, P.; Basset, Roland; Ledesma, C.; Ciurea, S; Parmar, S.; Shpall, EJ; Hosing, C.; Khouri, Issa; Qazilbash, M; Popat, U; Alousi, A.; Nieto, Y; Jones, RB; Lima, M.; Champlin, RE

    2012-01-01

    We investigated the safety and early disease-control data obtained with intravenous busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients with median age 36 years (range 20–64) received a matched sibling (n=24), syngeneic (n=2) or matched unrelated donor transplant (n=25) for ALL in first complete remission (n=30), second complete remission (n=13), or with active...

  18. Systematic Nutritional Support in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

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    Fuji, Shigeo; Einsele, Hermann; Savani, Bipin N; Kapp, Markus

    2015-10-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has become an established treatment modality for various hematological diseases. However, in allogeneic HSCT, patients often suffer from severe gastrointestinal complications caused by the conditioning regimen and acute/chronic graft-versus-host disease, which requires support by multidisciplinary nutritional support teams (NST). In addition, pretransplantation nutritional status can affect the clinical outcome after allogeneic HSCT. Therefore, it is important to refer the patient to a NST when becoming aware of nutritional problems before allogeneic HSCT. It is also important to follow nutritional status over the long term, as patients often suffer from various nutritional problems, such as malnutrition and metabolic syndrome, even late after allogeneic HSCT. In summary, NST can contribute to the improvement of nutritional status and possibly prognosis at every stage before and after allogeneic HSCT. Here, we aim to give a comprehensive overview of current understanding about nutritional support in allogeneic HSCT and try to provoke a constructive discussion to stimulate further investigation. PMID:26172477

  19. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sandra Fernandes

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT.

  20. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT.

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    Rasche, L; Kapp, M; Einsele, H; Mielke, S

    2014-02-01

    EBV-induced post transplantation lymphoproliferative disorder (EBV-PTLD) is a life-threatening complication after allogeneic hematopoietic cell transplantation. Profound T-cell depletion of the allograft represents a major risk factor for EBV-PTLD. With regard to the increasing use of alternative stem cell sources such as cord blood or purified haploidentical stem cell grafts both associated with impaired immune reconstitution, the frequent occurrence of EBV-PTLD demands particular vigilance on laboratory changes and early symptoms. Here we have summarized today's knowledge about EBV-PTLD in a comprehensive review explaining the underlying mechanisms of EBV-based transformation, EBV-PTLD development, clinical presentation, incidence, diagnosis, screening, therapy and prognosis. In this context, we emphasize on the necessity of regularly applied screening tools and pre-emptive treatment strategies including anti-CD20 Abs particularly in high-risk patients to avoid disease progression to malignant lymphoma. Although EBV-PTLD has always been associated with a high mortality rate, novel immunotherapeutic approaches such as the transfer of EBV-specific T cells nowadays offer improved chances of disease control even at late stages. PMID:23832092

  1. Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Tanaka, Takashi; Inamoto, Yoshihiro; Yamashita, Takuya; Fuji, Shigeo; Okinaka, Keiji; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Fukuda, Takahiro

    2016-05-01

    Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/μL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/μL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag. PMID:26785333

  2. Ikaros deficiency in host hematopoietic cells separates GVL from GVHD after experimental allogeneic hematopoietic cell transplantation

    OpenAIRE

    Toubai, Tomomi; Guoqing, Hou; Rossi, Corrine; Mathewson, Nathan; Oravecz-Wilson, Katherine; Cummings, Emily; Wu, Julia; Sun, Yaping; Choi, Sung; Reddy, Pavan

    2015-01-01

    The graft-versus-leukemia (GVL) effect following allogeneic hematopoietic stem cell transplantation (allo-HCT) is critical for its curative potential. Hwever, GVL is tightly linked to graft-versus-host disease (GVHD). Among hematological malignancies, acute lymphoblastic leukemia (ALL) is the most resistant to GVL, although the reasons for this remain poorly understood. Clinical studies have identified alterations in Ikaros (Ik) transcription factor as the major marker associated with poor ou...

  3. Etanercept for steroid-refractory acute graft versus host disease following allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Park, Joo Han; Lee, Hyo Jung; Kim, Sei Rhan; Song, Ga Won; Lee, Seung Kyong; Park, Sun Young; Kim, Ki Chan; Hwang, Sun Hyuk; Park, Joon Seong

    2014-01-01

    Background/Aims The treatment for steroid-refractory acute graft versus host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) needs to be standardized. We report our clinical experience with etanercept for steroid-refractory acute GVHD. Methods Eighteen patients who underwent allo-SCT and presented with steroid-refractory acute GVHD at Ajou University Hospital were studied retrospectively. They were given 25 mg of etanercept subcutaneously twice weekly for 4 weeks. The cli...

  4. 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 bioavailabil......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...

  5. Focal nodular hyperplasia of the liver: an emerging complication of hematopoietic SCT in children.

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    Pillon, M; Carucci, N S; Mainardi, C; Carraro, E; Zuliani, M; Chemello, L; Calore, E; Tumino, M; Varotto, S; Toffolutti, T; Destro, R; Gazzola, M V; Alaggio, R; Basso, G; Messina, C

    2015-03-01

    Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institution's case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients. PMID:25581411

  6. Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic SCT for AML and myelodysplastic syndrome.

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    Mo, X-D; Xu, L-P; Zhang, X-H; Liu, D-H; Wang, Y; Chen, H; Yan, C-H; Chen, Y-H; Han, W; Wang, F-R; Wang, J-Z; Liu, K-Y; Huang, X-J

    2015-01-01

    The aim of this study was to investigate the impact of occurrence of chronic GVHD (cGVHD) and its severity on transplantation outcomes in a consecutive cohort of AML and myelodysplastic syndrome (MDS) patients who received unmanipulated haploidentical hematopoietic SCT (haplo-HSCT; n=324). The cumulative incidence of relapse was significantly decreased in patients with cGVHD compared with the non-cGVHD group (1 year: 3.2% vs 11.9%, P=0.002; 3 years: 6.0% vs 16.3%, P=0.002), particularly in those with mild cGVHD. The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD. The probabilities of disease-free survival (DFS) were significantly better in patients with cGVHD than in those in the non-cGVHD group (1 year: 90.5% vs 78.5%, P=0.002; 3 years: 86.5% vs 71.5%, PGVL effect in patients with AML and MDS receiving unmanipulated haplo-HSCT; however, only mild or moderate cGVHD was associated with a lower risk of relapse translating into improved DFS. PMID:25387095

  7. Bullous pemphigoid after allogeneic hematopoietic stem cell transplantation.

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    Kato, Keisuke; Koike, Kazutoshi; Kobayashi, Chie; Iijima, Shigeruko; Hashimoto, Takashi; Tsuchida, Masahiro

    2015-06-01

    Bullous pemphigoid (BP) is an autoimmune skin disorder characterized by subepidermal blisters due to deposit of autoantibody against dermal basement membrane protein. It has been reported that BP can occur after allogeneic hematopoietic stem cell transplantation (HSCT). We describe a patient with BP having autoantibody against BP180 after unrelated-donor HSCT against T lymphoblastic leukemia. The patient was treated with steroid leading to complete resolution of BP, but T lymphoblastic leukemia progressed rapidly after steroid hormone treatment. Given that immunosuppressant may reduce graft-versus-tumor effect, immunomodulatory agents such as nicotinamide and tetracycline, erythromycin, and immunoglobulin may be appropriate as soon as typical blister lesions are seen after HSCT. PMID:26113316

  8. Engraftment syndrome after allogeneic hematopoietic cell transplantation predicts poor outcomes.

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    Chang, Lawrence; Frame, David; Braun, Thomas; Gatza, Erin; Hanauer, David A; Zhao, Shuang; Magenau, John M; Schultz, Kathryn; Tokala, Hemasri; Ferrara, James L M; Levine, John E; Reddy, Pavan; Paczesny, Sophie; Choi, Sung Won

    2014-09-01

    Engraftment syndrome (ES), characterized by fever, rash, pulmonary edema, weight gain, liver and renal dysfunction, and/or encephalopathy, occurs at the time of neutrophil recovery after hematopoietic cell transplantation (HCT). In this study, we evaluated the incidence, clinical features, risk factors, and outcomes of ES in children and adults undergoing first-time allogeneic HCT. Among 927 patients, 119 (13%) developed ES at a median of 10 days (interquartile range 9 to 12) after HCT. ES patients experienced significantly higher cumulative incidence of grade 2 to 4 acute GVHD at day 100 (75% versus 34%, P HCT outcomes. Despite early recognition of the syndrome and prompt institution of corticosteroid therapy, outcomes in ES patients were uniformly poor. This study suggests the need for a prospective approach of collecting clinical features combined with correlative laboratory analyses to better characterize ES. PMID:24892262

  9. Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Concurrent Lymphoid Malignancy

    OpenAIRE

    Zimmerman, Zachary; Scott, Bart L.; Gopal, Ajay K.; Sandmaier, Brenda M.; Maloney, David G; Deeg, H. Joachim

    2011-01-01

    Allogeneic hematopoietic cell transplantation (HCT) can be curative for both myelodysplastic syndromes (MDS) and lymphoid malignancies. Little is known about the efficacy of allogeneic HCT in patients in whom both myeloid and lymphoid disorders are present at the time of HCT. We analyzed outcomes in 21 patients with MDS and concurrent lymphoid malignancy when undergoing allogeneic HCT. Seventeen patients had received extensive prior cytotoxic chemotherapy, including autologous HCT in seven, f...

  10. 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....

  11. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioni...

  12. Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades.

    Science.gov (United States)

    Svenberg, Petter; Remberger, Mats; Uzunel, Mehmet; Mattsson, Jonas; Gustafsson, Britt; Fjaertoft, Gustav; Sundin, Mikael; Winiarski, Jacek; Ringdén, Olle

    2016-08-01

    Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT. PMID:27251184

  13. Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children.

    Science.gov (United States)

    de Koning, Coco; Plantinga, Maud; Besseling, Paul; Boelens, Jaap Jan; Nierkens, Stefan

    2016-02-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) has evolved into a potent curative treatment option for a variety of malignant and nonmalignant diseases. The occurrence of complications and mortality after allo-HCT is, however, still high and is strongly associated with immune reconstitution (IR). Therefore, detailed information on IR through immunomonitoring is crucial to improve survival chances after HCT. To date, information about the reconstituting immune system after allo-HCT in pediatric patients is mostly derived from routine standard-of-care measurements. More profound knowledge on IR may provide tools to better predict and modulate adverse reactions and, subsequently, improve survival chances. Here, we provide an overview of IR (eg, immune cell subsets and circulating chemokines/cytokines) after allo-HCT in children, taking into account different cell sources and serotherapy, and discuss strategies to enhance immunomonitoring. We conclude that available IR data after allo-HCT contain limited information on immune cell families (mostly only generic T, B, and NK cells), which would improve with more detailed information on reconstituting cell subsets or effector cell functionality at earlier time points (functionality and may even provide (early) biomarkers for individual disease outcome, such as viral reactivity, graft-versus-host disease, or graft-versus-leukemia. The present data and suggestions for more detailed, standardized, and harmonized immunomonitoring in future (pediatric) allo-HCT studies will pave the path to "precision transplantation:" an individualized HCT approach (including conditioning), based on detailed information on IR and biomarkers, aiming to reduce transplantation related mortality and relapse, and subsequently improve survival chances. PMID:26341398

  14. Allogeneic hematopoietic stem cell transplantation for primary cutaneous T cell lymphomas

    OpenAIRE

    Paralkar, Vikram R.; Nasta, Sunita Dwivedy; Morrissey, Kelly; Smith, Jacqueline; Vassilev, Pavel; Martin, Mary Ellen; Goldstein, Steven C.; Loren, Alison; Rook, Alain H.; Kim, Ellen J.; Porter, David L.

    2011-01-01

    Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of non-Hodgkin lymphomas that are considered incurable. The role of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of CTCL is not well defined but may provide potent graft-vs-lymphoma (GVL) activity independent of the conditioning therapy. We present outcomes of 12 extensively-pretreated patients with CTCL who underwent allogeneic HSCT using, most commonly, a reduced intensity conditioning (RIC) regimen. M...

  15. Ten years after the first inspection of a candidate European centre, an EBMT registry analysis suggests that clinical outcome is improved when hematopoietic SCT is performed in a JACIE accredited program.

    Science.gov (United States)

    Chabannon, C; Pamphilon, D; Vermylen, C; Gratwohl, A; Niederwieser, D; McGrath, E; Lamers, C; Lanza, F; Slaper-Cortenbach, I; Madrigal, A; Apperley, J

    2012-01-01

    In 2010, JACIE, the Joint Accreditation Committee of ISCT (International Society for Cell Therapy) Europe and EBMT (European group for Blood and Marrow Transplantation) celebrated the tenth anniversary of the first inspection of a European hematopoietic SCT program. JACIE standards establish the criteria for a comprehensive quality management program that covers all three major domains of activity that are necessary for the delivery of HSCT: clinical, collection and processing, as well as their interactions with ancillary and supportive activities. Although more than 200 European programs have applied for JACIE accreditation, and more than 100 have been granted accreditation, a recent retrospective analysis of the large-size EBMT registry of autologous and allogenic hematopoietic HSCT demonstrates that one of the factors affecting the overall survival of recipients of allogenic transplantation is the status of the transplant program regarding JACIE accreditation. This provides one of the first demonstrations that introduction of a quality management system contributes to the overall survival of patients treated with a highly specific medical procedure, and represents a milestone in the implementation of JACIE. PMID:21383685

  16. 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...

  17. A problem-solving education intervention in caregivers and patients during allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Bevans, Margaret; Wehrlen, Leslie; Castro, Kathleen; Prince, Patricia; Shelburne, Nonniekaye; Soeken, Karen; Zabora, James; Wallen, Gwenyth R.

    2013-01-01

    The aim of this study was to determine the effect of problem-solving education on self-efficacy and distress in informal caregivers of allogeneic hematopoietic stem cell transplantation patients. Patient/caregiver teams attended three 1-hour problem-solving education sessions to help cope with problems during hematopoietic stem cell transplantation. Primary measures included the Cancer Self-Efficacy Scale–transplant and Brief Symptom Inventory–18. Active caregivers reported improvements in se...

  18. Prognostic value of pretransplant serum C-reactive protein in patients receiving reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Yamamoto, Wataru; Fujii, Eriko; Matsumoto, Kenji; Yamamoto, Eri; Aoki, Jun; Tanaka, Masatsugu; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2016-04-01

    The impact of pre-transplant serum C-reactive protein (CRP) level on the outcome of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC allo-SCT) is unclear. This study retrospectively investigated 78 patients who underwent RIC allo-SCT between 2005 and 2013. The conditioning regimen consisted of fludarabine and melphalan with/without total body irradiation. The 3-year overall survival of high CRP (43.6 % of all patients) patients was significantly worse than that of normal CRP patients in whom CRP was ≤0.3 mg/dl (26.7 vs. 74.1 %, P level before transplantation and disease risk status were independent prognostic factors for overall survival by multivariate analysis. CRP was not a significant predictor of NRM by multivariate analysis (hazard ratio 3.2, 95 % confidence interval 0.8-13.1, P = 0.100). These results suggest that measuring the CRP level before transplantation can be useful to predicting the outcome of RIC allo-SCT. PMID:26791379

  19. Sequential myeloablative autologous stem cell transplantation and reduced intensity allogeneic hematopoietic cell transplantation is safe and feasible in children, adolescents and young adults with poor-risk refractory or recurrent Hodgkin and non-Hodgkin lymphoma.

    Science.gov (United States)

    Satwani, P; Jin, Z; Martin, P L; Bhatia, M; Garvin, J H; George, D; Chaudhury, S; Talano, J; Morris, E; Harrison, L; Sosna, J; Peterson, M; Militano, O; Foley, S; Kurtzberg, J; Cairo, M S

    2015-02-01

    The outcome of children, adolescents and young adults (CAYA) with poor-risk recurrent/refractory lymphoma is dismal (⩽30%). To overcome this poor prognosis, we designed an approach to maximize an allogeneic graft vs lymphoma effect in the setting of low disease burden. We conducted a multi-center prospective study of myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT), followed by a reduced intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (AlloHCT) in CAYA, with poor-risk refractory or recurrent lymphoma. Conditioning for MAC AutoSCT consisted of carmustine/etoposide/cyclophosphamide, RIC consisted of busulfan/fludarabine. Thirty patients, 16 Hodgkin lymphoma (HL) and 14 non-Hodgkin lymphoma (NHL), with a median age of 16 years and median follow-up of 5years, were enrolled. Twenty-three patients completed both MAC AutoSCT and RIC AlloHCT. Allogeneic donor sources included unrelated cord blood (n=9), unrelated donor (n=8) and matched siblings (n=6). The incidence of transplant-related mortality following RIC AlloHCT was only 12%. In patients with HL and NHL, 10 year EFS was 59.8% and 70% (P=0.613), respectively. In summary, this approach is safe, and long-term EFS with this approach is encouraging considering the poor-risk patient characteristics and the use of unrelated donors for RIC AlloHCT in the majority of cases. PMID:24938649

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  1. 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. In this...

  2. Plasmacytoid dendritic cells in allogeneic hematopoietic cell transplantation: benefit or burden?

    Science.gov (United States)

    Auletta, JJ; Devine, SM; Waller, EK

    2016-01-01

    Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and have important roles in hematopoietic engraftment, GvHD and graft-versus-leukemia responses following allogeneic hematopoietic cell transplantation (HCT). In addition, pDCs mediate antiviral immunity, particularly as they are the body’s primary cellular source of type I interferon. Given their pleiotropic roles, pDCs have emerged as cells that critically impact transplant outcomes, including overall survival. In this article, we will review the pre-clinical and clinical literature, supporting the crucial roles that pDCs assume as key immune effector cells during HCT. PMID:26642333

  3. Hyperbaric oxygen: an important treatment modality in severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Deniz Sargın; Murat Tunç; Nuray Gürses; Oktay Perdeci; Sevgi Kalayoğlu-Beşışık; Mustafa Nuri Yenerel

    2009-01-01

    Objective: Hemorrhagic cystitis (HC) is a generally self-limited complication of hematopoietic stem cell transplantation (HSCT). It may occur in the early or late posttransplant period and can promote sometimes severe morbidity. We analyzed our data regarding HC in allogeneic HSCT patients in order to establish the efficacy of hyperbaric oxygen (HBO) therapy in severe HC and to document the main problems during its use. Material and Methods: Between March 1993 and August 2006, 161 patients re...

  4. Methods and biomarkers for outcome prediction after allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Sairafi, Darius

    2012-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a potent immunotherapeutic procedure but its usability is limited by a high risk of serious complications. A prerequisite for timely initiation of preventive measures is the availability of predictive methods. This thesis aims to evaluate techniques that may potentially be used to assess the risk of some of these complications on the individual level. Defective function of the pattern recognition receptor NOD2, due to natural...

  5. Herpesvirus-Associated Central Nervous System Diseases after Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Meiqing Wu; Fen Huang; Xinmiao Jiang; Zhiping Fan; Hongsheng Zhou; Can Liu; Qianli Jiang; Yu Zhang; Ke Zhao; Li Xuan; Xiao Zhai; Fuhua Zhang; Changxin Yin; Jing Sun; Ru Feng

    2013-01-01

    Herpesvirus infections of the central nervous system (CNS) are associated with encephalitis/myelitis and lymphoproliferative diseases in immunocompromised individuals. As of now, data of herpesvirus-associated CNS diseases in transplant recipients is limited. Hence, in this prospective study, we investigated the incidence of herpesvirus-associated CNS diseases and explored the diagnosis of these diseases in 281 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Herpesv...

  6. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle; Buchvald, Frederik Fouirnaies; Nielsen, Kim Gjerum; Heilmann, Carsten Johan; Müller, Klaus Gottlob

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  7. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...... therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....

  8. Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia.

    Science.gov (United States)

    Rotz, S J; O'Riordan, M A; Kim, C; de Lima, M; Gladwin, M T; Little, J A

    2015-07-01

    Estimating prognosis in sickle cell anemia (SCA) assumes greater importance as intensive treatments, such as hematopoietic SCT (HSCT), are being tested. Here we estimate the mortality risk from the walk-PHaSST (Sildenafil Therapy for Pulmonary Hypertension and Sickle Cell Disease) trial of homozygous SCA patients with suspected pulmonary hypertension (19/468 deaths; 10 centers in the US and UK). Parallel investigations were also undertaken in the Cooperative Study of Sickle Cell Disease (CSCCD) and a contemporary urban sickle cell disease population (Case Western Reserve University-University Hospitals (CWRU-UH), Cleveland, OH, USA). One- and two-value positive predictive values for 2-year mortality (from study entry) are calculated using factors that include demographics, laboratory values and clinical evaluations. We define high-, intermediate-, and low-risk SCA as > 15%, 10-15% and 35 years and history of chronic transfusion) do. Either elevated white blood cell count (> 13.5 × 10(3) cells/mcL, 7/70 deaths) or elevated Tricuspid Regurgitant Jet Velocity (⩾ 3.0 m/s, 8/67 deaths) was individually associated with intermediate-risk disease, as were many two-factor combinations. N-terminal pro-brain natriuretic peptide > 160 ng/L, lactate dehydrogenase > 600 IU/L, history of chronic transfusion, sepsis or age > 35 years are individually associated with low-risk SCA, as are many two-factor combinations. SCA risk was integrated with estimated donor type-associated risk from HSCT to form 'Traffic Light' eligibility criteria for clinical trials of HSCT. This method is adaptable to evolutions in clinical care. PMID:25774596

  9. Neutrophil function in children following allogeneic hematopoietic stem cell transplant.

    Science.gov (United States)

    Kent, Michael W; Kelher, Marguerite R; Silliman, Christopher C; Quinones, Ralph

    2016-08-01

    HSCT is a lifesaving procedure for children with malignant and non-malignant conditions. The conditioning regimen renders the patient severely immunocompromised and recovery starts with neutrophil (PMN) engraftment. We hypothesize that children demonstrate minimal PMN dysfunction at engraftment and beyond, which is influenced by the stem cell source and the conditioning regimen. Peripheral blood was serially collected from children at 1 to 12 months following allogeneic HSCT. PMN superoxide (O2-) production, degranulation (elastase), CD11b surface expression, and phagocytosis were assessed. Twenty-five patients, mean age of 10.5 yr with 65% males, comprised the study and transplant types included: 14 unrelated cord blood stem cells (cords), seven matched related bone marrow donors, three matched unrelated bone marrow donors, and one peripheral blood progenitor cells. Engraftment occurred at 24 days. There were no significant differences between controls and patients in PMN O2- production, phagocytosis, CD11b surface expression, and total PMN elastase. Elastase release was significantly decreased <6 months vs. controls (p < 0.05) and showed normalization by six months for cords only. The conditioning regimen did not affect PMN function. PMN function returns with engraftment, save elastase release, which occurs later related to the graft source utilized, and its clinical significance is unknown. PMID:27114335

  10. Physiological problems in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sevgisun Kapucu

    2014-01-01

    Full Text Available Objective: Stem cell transplantation is usually performed in an effort to extend the patient′s life span and to improve their quality of life. This study was conducted to determine the postoperative physiological effects experienced by patients who had undergone autologous and allogeneic stem cell transplantation. Methods: The research is a descriptive study conducted with a sample of 60 patients at Stem Cell Transplantation Units in Ankara. Percentile calculation and chi-square tests were used to evaluate the data. Results: When a comparison was made between patients who had undergone allogeneic Hematopoietic stem cell transplantation (HSCT and those who had undergone autologous HSCT, results indicated that problems occurred more often for the allogeneic HSCT patients. The problems included: Digestion (94.3%, dermatological (76.7%, cardiac and respiratory (66.7%, neurological (66.7%, eye (56.7%, infections (26.7% and Graft Versus Host Disease (5 patients. Furthermore, the problems with pain (50%, numbness and tingling (40%, and speech disorders (3 patients were observed more often in autologous BMT patients. Conclusion: Autologous and allogeneic patients experienced most of physical problems due to they receive high doses of chemotherapy. Therefore, it is recommended that an interdisciplinary support team approach should be usedtohelp reduce and manage the problems that may arise during patient care.

  11. 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; Ravnborg, M; Sellebjerg, F; Vindeløv, L

    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....

  12. Pneumothorax in an early phase after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ebihara

    2013-06-01

    Full Text Available Pneumothorax is very rare after early phase of hematopoietic stem cell transplantation (HSCT and usually accompanied with pulmonary chronic graft-versus-host disease (GVHD, such as bronchiolitis obliterans and bronchiolitis obliterans organizing pneumonia. The present study describes the case of a seventeen-year-old male diagnosed with acute myeloid leukemia who underwent allogeneic bone marrow transplantation (BMT. Pneumothorax occurred at day 43 after BMT. Pneumothorax occurred in early phase of HSCT is extremely rare. The early onset of acute GVHD and the entity of cytomegalovirus might worsen the pulmonary tissue damages for the onset of pneumothorax, indicating that we should be aware of the possibility to occur pneumothorax even in the early period after allogeneic HSCT.

  13. Association of HMGB1 polymorphisms with outcome after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Kornblit, Brian Thomas; Masmas, Tania; Petersen, Søren;

    2010-01-01

    activation of antigen presenting cells (APCs) and propagation of inflammation. HMGB1 is implicated in the pathophysiology of a variety of inflammatory diseases, and we have recently found the variation in the HMGB1 gene to be associated with mortality in patients with systemic inflammatory response syndrome......Several studies have demonstrated that genetic variation in cytokine genes can modulate the immune reactions after allogeneic hematopoietic cell transplantation (HCT). High mobility group box 1 protein (HMBG1) is a pleiotropic cytokine that functions as a pro-inflammatory signal, important for the...

  14. Replacement of hematopoietic system by allogeneic stem cell transplantation in myelofibrosis patients induces rapid regression of bone marrow fibrosis

    OpenAIRE

    Kröger Nicolaus; Kvasnicka Michael; Thiele Jürgen

    2012-01-01

    Abstract Bone marrow fibrosis is a hallmark of primary and post ET/PV myelofibrosis. To investigated the impact of replacement of the hematopoietic system in myelofibrosis patients by allogeneic stem cell transplantation on bone marrow fibrosis, we studied bone marrow fibrosis on bone marrow samples from 24 patients with myelofibrosis before and after dose-reduced conditioning followed by allogeneic stem cell transplantation from related or unrelated donor. Using the European Consensus on Gra...

  15. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

    OpenAIRE

    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type ha...

  16. Incidence, etiology, and outcome of pleural effusions in allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Modi, Dipenkumar; Jang, Hyejeong; Kim, Seongho; Deol, Abhinav; Ayash, Lois; Bhutani, Divaya; Lum, Lawrence G; Ratanatharathorn, Voravit; Manasa, Richard; Mellert, Kendra; Uberti, Joseph P

    2016-09-01

    Pleural effusion is a known entity in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT); however, the incidence, risk factors, and morbidity-mortality outcomes associated with pleural effusions remain unknown. We retrospectively evaluated pleural effusions in 618 consecutive adult patients who underwent allogeneic HSCT from January 2008 to December 2013 at our institution. Seventy one patients developed pleural effusion at a median of 40 days (range, 1 - 869) post-HSCT with the cumulative incidence of 9.9% (95% CI, 7.7 - 12.5%) at 1 year. Infectious etiology was commonly associated with pleural effusions followed by volume overload and serositis type chronic GVHD. In multivariate analysis, higher comorbidity index (P = 0.03) and active GVHD (P = 0.018) were found to be significant independent predictors for pleural effusion development. Higher comorbidity index, very high disease risk index, ≤7/8 HLA matching, and unrelated donor were associated with inferior overall survival (OS) (P < 0.03). More importantly, patients with pleural effusion were noted to have poor OS in comparison to patients without pleural effusion (P < 0.001). Overall, pleural effusion is a frequently occurring complication after allogeneic HSCT, adding to morbidity and mortality and hence, early identification is required. Am. J. Hematol. 91:E341-E347, 2016. © 2016 Wiley Periodicals, Inc. PMID:27238902

  17. Allogeneic Hematopoietic Stem-Cell Transplantation for Myelofibrosis: A Practical Review.

    Science.gov (United States)

    Farhadfar, Nosha; Cerquozzi, Sonia; Patnaik, Mrinal; Tefferi, Ayalew

    2016-07-01

    Myelofibrosis is a myeloproliferative neoplasm with cardinal features of extramedullary hematopoiesis, hepatosplenomegaly, cytopenias, and constitutional symptoms that result in shortened survival and leukemic transformation. It is a disease predominantly of the elderly, and currently available therapies only offer symptom control without curative benefit or ability to alter disease progression. Allogeneic hematopoietic stem-cell transplant (HSCT) is the only potentially curative intervention; however, this is only feasible in younger and medically fit patients and selectively offered to those with high-risk disease. Despite ongoing advancements, HSCT is associated with substantial morbidity and mortality, and the determination of which patients with myelofibrosis are ideal candidates and the selection of the opportune moment to proceed with transplantation remains challenging. This review summarizes our current recommendations for the role of and indications for HSCT in myelofibrosis. PMID:27407157

  18. Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Lucarelli, Barbarella; Merli, Pietro; Bertaina, Valentina; Locatelli, Franco

    2016-03-01

    The interplay existing between immune reconstitution and patient outcome has been extensively demonstrated in allogeneic hematopoietic stem cell transplantation. One of the leading causes of infection-related mortality is the slow recovery of T-cell immunity due to the conditioning regimen and/or age-related thymus damage, poor naïve T-cell output, and restricted T-cell receptor (TCR) repertoires. With the aim of improving posttransplantation immune reconstitution, several immunotherapy approaches have been explored. Donor leukocyte infusions are widely used to accelerate immune recovery, but they carry the risk of provoking graft-versus-host disease. This review will focus on sophisticated strategies of thymus function-recovery, adoptive infusion of donor-derived, allodepleted T cells, T-cell lines/clones specific for life-threatening pathogens, regulatory T cells, and of T cells transduced with suicide genes. PMID:26588325

  19. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle;

    2015-01-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National...... Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies...... vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients...

  20. Management of Viral Infections in Allogenic Hematopoietic Stem Cell Transplanted Children

    Directory of Open Access Journals (Sweden)

    Hatice Hale Gumus

    2014-02-01

    Full Text Available Viral infections such as herpes viruses (CMV, EBV, HHV-6, HSV-1 and 2, VZV, adenovirus, and polyomavirus (BK virus may lead to considerable morbidity and mortality in allogenic hematopoietic stem cell transplanted children (HSCT, mainly due to iatrogenic T cell dysfunction. To manage these infections, different strategies like matching of host and donor, viral surveillance, antiviral prophylaxis and preemptive antiviral treatment have been tried and combined, since these infections have become more recognised and can be monitored by quantitative real-time polymerase chain reaction. Viral infections associated with high morbidity and mortality in HSCT patients can be prevented by early diagnosis through the molecular diagnostic techniques and timely initiation of appropriate treatment options.

  1. Hyperbaric oxygen: an important treatment modality in severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Deniz Sargın

    2009-12-01

    Full Text Available Objective: Hemorrhagic cystitis (HC is a generally self-limited complication of hematopoietic stem cell transplantation (HSCT. It may occur in the early or late posttransplant period and can promote sometimes severe morbidity. We analyzed our data regarding HC in allogeneic HSCT patients in order to establish the efficacy of hyperbaric oxygen (HBO therapy in severe HC and to document the main problems during its use. Material and Methods: Between March 1993 and August 2006, 161 patients received allogeneic HSCT. Mesna, hyperhydration and forced diuresis were used as early HC prophylaxis of cyclophosphamide-induced HC. However, HC was diagnosed in 49 of the 161 recipients and 17 of them were considered as severe HC. We analyzed their data retrospectively.Results: Forced diuresis with hyperhydration (up to 8 L/day and transfusion support to maintain a platelet count above 30x109/L were sufficient in 10 of the 17 patients with severe HC. Alternative therapies used included intravesical irrigation with formalin and prostaglandin (PGF2 alpha and HBO, and HBO appeared to be the most useful among them. Conclusion: We conclude that HBO offers a noninvasive therapeutic alternative in the management of intractable HC in the HSCT setting.

  2. DNA Damage and Repair in Epithelium after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Maria Themeli

    2012-11-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (allo-HSCT in humans, following hematoablative treatment, results in biological chimeras. In this case, the transplanted hematopoietic, immune cells and their derivatives can be considered the donor genotype, while the other tissues are the recipient genotype. The first sequel, which has been recognized in the development of chimerical organisms after allo-HSCT, is the graft versus host (GvH reaction, in which the new developed immune cells from the graft recognize the host’s epithelial cells as foreign and mount an inflammatory response to kill them. There is now accumulating evidence that this chronic inflammatory tissue stress may contribute to clinical consequences in the transplant recipient. It has been recently reported that host epithelial tissue acquire genomic alterations and display a mutator phenotype that may be linked to the occurrence of a GvH reaction. The current review discusses existing data on this recently discovered phenomenon and focuses on the possible pathogenesis, clinical significance and therapeutic implications.

  3. Exploiting HLA-class II disparity for anti-tumor immunity by allogeneic cellular immunotherapy

    OpenAIRE

    Stevanović, Sanja

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment for various hematological malignancies. The beneficial Graft-versus-Leukemia (GvL) effect of alloSCT is mediated by donor-derived allo-reactive T cells targeting the malignant cells of the patient. Unfortunately, detrimental Graft-versus-Host-Disease (GvHD) often co-develops due to recognition of allo-antigens by donor-derived T cells on non-hematopoietic tissues. To prevent the development of GvH...

  4. Impact of Gut Colonization by Antibiotic-Resistant Bacteria on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective, Single-Center Study.

    Science.gov (United States)

    Bilinski, Jaroslaw; Robak, Katarzyna; Peric, Zinaida; Marchel, Halina; Karakulska-Prystupiuk, Ewa; Halaburda, Kazimierz; Rusicka, Patrycja; Swoboda-Kopec, Ewa; Wroblewska, Marta; Wiktor-Jedrzejczak, Wieslaw; Basak, Grzegorz W

    2016-06-01

    Gut colonization by antibiotic-resistant bacteria may underlie hard-to-treat systemic infections. There is also accumulating evidence on the immunomodulatory function of gut microbiota after allogeneic stem cell transplantation (alloSCT) and its impact on graft-versus-host disease (GVHD). We investigated the epidemiology and clinical impact of gut colonization after alloSCT and retrospectively analyzed data on 107 alloSCTs performed at a single transplant center. Pretransplant microbiology screening identified colonization in 31% of cases. Colonization had a negative impact on overall survival after alloSCT in univariate (34% versus 74% at 24 months, P antibiotic-resistant bacteria decreases the overall survival of patients undergoing alloSCT by increasing nonrelapse mortality and the incidences of systemic infection and acute GVHD. PMID:26900084

  5. Impact of Pretransplant Donor and Recipient Cytomegalovirus Serostatus on Outcome for Multiple Myeloma Patients Undergoing Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation

    OpenAIRE

    El-Cheikh, Jean; Devillier, Raynier; Crocchiolo, Roberto; Fürst, Sabine; Calmels, Boris; Faucher, Catherine; Stoppa, Anne Marie; Granata, Angela; Castagna, Luca; Ladaique, Patrick; Lemarie, Claude; Bouabdallah, Reda; Zandotti, Christine; Merlin, Michele; Berger, Pierre

    2013-01-01

    Scope of the study was to investigate the impact of pre-transplant CMV serostatus of the donor and/or recipient on the outcome of patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-SCT) for Multiple Myeloma (MM). To our knowledge no data are available in the literature about this issue. We retrospectively followed 99 consecutive patients who underwent reduced-intensity conditioning (RIC) Allo-SCT for MM in our cancer center at Marseille between January 2000 and Janua...

  6. Controversies in autologous and allogeneic hematopoietic cell transplantation in peripheral T/NK-cell lymphomas.

    Science.gov (United States)

    Shustov, Andrei

    2013-03-01

    Peripheral T-cell and NK-cell lymphomas (PT/NKCL) are a heterogeneous group of lymphoid neoplasms with poor outcomes. There is no consensus on the best front line therapy or management of relapsed/refractory disease. The use of autologous and allogeneic hematopoietic cell transplantation (HCT) has been studied in both settings to improve outcomes. Multiple retrospective and several prospective trials were reported. While at first sight the outcomes in the relapsed/refractory setting appear similar in B-cell and T-cell lymphomas when treated with high dose therapy (HDT) and autologous HCT, it is becoming obvious that only specific subtypes of PTCL benefit from this approach (i.e. anaplastic large cell lymphoma [ALCL] and angioimmunoblastic lymphoma [AITL] in second CR). In less favorable histologies, HDT seems to provide limited benefit, with the majority of patients experiencing post-transplant relapse. The use of autologous HCT to consolidate first remission has been evaluated in several prospective trials. Again, the best results were observed in ALCL, but the superiority of this approach over chemotherapy alone needs confirmation in randomized trials. In less favorable histologies, high-dose consolidation resulted in low survival rates comparable to those obtained with chemotherapy alone, and without randomized trials it is hard to recommend this strategy to all patients with newly diagnosed PT/NKCL. Allogeneic HCT might provide potent and potentially curative graft-vs-lymphoma effect and overcome chemotherapy resistance. Only a few studies have been reported to date on allogeneic HCT in PT/NKCL. Based on available data, eligible patients benefit significantly from this approach, with 50% or more patients achieving long-term disease control or cure, although at the expense of significant treatment related mortality (TRM). Reduced-intensity conditioning regimens appear to have lower TRM and might extend this approach to older patients. With the recent approval of

  7. Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis.

    Science.gov (United States)

    Shimizu, Hiroaki; Saitoh, Takayuki; Machida, Shinichiro; Kako, Shinichi; Doki, Noriko; Mori, Takehiko; Sakura, Toru; Kanda, Yoshinobu; Kanamori, Heiwa; Miyawaki, Shuichi; Okamoto, Shinichiro

    2015-11-01

    Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo-SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo-SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method. The 5-yr overall survival (OS) rate of patients with MPAL was 48.1%, and patients in remission at the time of transplant showed significantly better survival than those not in remission (5-yr OS: 71.8% vs. 0%, P = 0.001). No significant differences were seen in OS when stratifying patients according to immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The 5-yr OS rate of patients with MPAL was not significantly different compared with AML control patients (48.1% vs. 48.1%; P = 0.855) or ALL control patients (48.1% vs. 37.8%; P = 0.426). These results suggested that allo-SCT is an effective treatment for MPAL, especially early in the disease course, and innovative transplant approaches are warranted to improve the transplant outcome of patients with MPAL who are not in remission. PMID:25605541

  8. Implementation of JACIE accreditation results in the establishment of new indicators that unevenly monitor processes contributing to the delivery of hematopoietic SCT.

    Science.gov (United States)

    Caunday, O; Agulles, O; McGrath, E; Empereur, F; Stoltz, J F; Chabannon, C

    2013-04-01

    More than 145 European hematopoietic SCT programs have received JACIE (Joint Accreditation Committee for ISCT Europe and EBMT) accreditation since 2000, demonstrating compliance with FACT (Foundation for the Accreditation of Cell Therapy)-JACIE international standards. The association of JACIE with improved patient outcome was recently documented. However, conditions in which quality management systems were introduced and the actual benefits remain to be fully evaluated. Our study focuses on one aspect of quality management: introduction and use of indicators. Through a questionnaire sent to JACIE-accredited centers and responses from 32 programs (or 40%), we identified 293 indicators, including 224 (76%) that were introduced during the preparatory phase of JACIE accreditation. Indicators were associated with the following processes: measurement, analysis and improvement (54/293 or 18%); donor collection (49/293 or 16%); processing and storage of cell therapy products (37/293 or 12.5%); and administration of hematopoietic progenitor cells (67/293 or 23%). Mapping revealed an uneven distribution of indicators across the different subprocesses that contribute to this highly specialized medical procedure. Moreover, we found that only 101/293 indicators (34%) complied with the rules for implementation of a quality indicator, as defined by the FDX 50-171 standard. This suggests that risks to donors/recipients are unevenly monitored, leaving critical medical steps with low levels of monitoring. PMID:23528642

  9. Comparison of itraconazole, voriconazole, and posaconazole as oral antifungal prophylaxis in pediatric patients following allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    M. Döring; Blume, O; Haufe, S.; Hartmann, U; Kimmig, A.; Schwarze, C.-P.; Lang, P; Handgretinger, R; Müller, I

    2013-01-01

    Oral antifungal prophylaxis with extended-spectra azoles is widely used in pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), while controlled studies for oral antifungal prophylaxis after bone marrow transplantation in children are not available. This survey analyzed patients who had received either itraconazole, voriconazole, or posaconazole. We focused on the safety, feasibility, and initial data of efficacy in a cohort of pediatric patients and adolescents...

  10. Prognostic significance of interleukin-7 receptor-α gene polymorphisms in allogeneic stem-cell transplantation: a confirmatory study

    DEFF Research Database (Denmark)

    Shamim, Zaiba; Ryder, Lars P; Christensen, Ib J;

    2011-01-01

    BACKGROUND: Interleukin-7 (IL-7) is a hematopoietic cytokine essential for T-cell development in the thymus and for the maintenance of peripheral T cells. A previous study of single nucleotide polymorphisms in the exons of IL-7 receptor a-chain (IL-7Ra) in a Danish cohort of patients undergoing...... allogeneic stem-cell transplantation (SCT) identified donor genotype GG at rs1494555 as a risk factor for treatment-related mortality (TRM) after SCT. METHODS: In this validation study, 116 British and French SCT patients and their donors were investigated by sequence-specific primer polymerase chain...

  11. [A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hematopoietic stem cell transplantation in adults: a cross-reflection on our organizations].

    Science.gov (United States)

    Bourget, Philippe; Falaschi, Ludivine; Suarez, Felipe; Galland, Valérie; Blot, Dominique; Trompette, Caroline; Sibon, David; Fontbrune, Flore Sicre de; Merlette, Christophe; Vidal, Fabrice; Corriol, Odile; Giraud, Bérénice; Broissand, Christine; Clement, Rozenn; Hermine, Olivier

    2012-06-01

    Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure for many hematological malignancies and some benign and congenital diseases. Busulfan, proposed in its injectable form, has quickly become a mainstay of pharmacological and myeloablative (or non-myeloablative) conditioning. This is following the outbreak in 2010 of a multicenter international clinical phase II trial, we tested the robustness and reliability of our organization in a complex model of organization and multifactorial partnership. In this type "BuCy2" protocol based on a classical treatment duration of 4 consecutive days, the administration of IV busulfan is given in one single daily infusion instead of the conventional 16 infusions, while keeping the same total dose. Under these conditions, the treatment is totally secured using a therapeutic drug monitoring of busulfan, applied in real-time. The process is technically complex and requires the very close cooperation of the teams involved. A strength, weakness, opportunity and threat (SWOT) analysis has been constructed; it fully supports continuous quality improvement to the triple benefit of the nursing chain, the patients and their environment. Several critical points were identified and corrected. The experiment strongly contributes to the safety and security of the medication circuit at the hospital and, improves the performance of allo-SCT. It also contributes to the protection of all actors in the health field and their working environment via a well-functioning quality management system. PMID:22645281

  12. Allogeneic hematopoietic cell transplantation in patients with myelofibrosis: A single center experience.

    Science.gov (United States)

    Schmohl, Joerg U; Groh, Christiane; Faul, Christoph; Vogel, Wichard; Möhle, Robert; Wirths, Stefan; Schneidawind, Dominik; Kanz, Lothar; Bethge, Wolfgang A

    2016-05-01

    Myelofibrosis (MF) is a rare disease responsible for an increasing ineffective hematopoesis by a progressive fibrosing process in the bone marrow. The only curative treatment option is allogeneic hematopoietic cell transplantation (HCT). In this single-center analysis, we evaluated retrospectively 54 consecutive patients suffering from primary or secondary MF which underwent HCT from 1997 to 2014 after either myeloablative (MAC, n = 19) or reduced-intensity conditioning (RIC, n = 35). Overall survival (OS) and disease-free survival (DFS) after 3 years was 54/53 % for RIC versus 63/58 % for MAC (p = 0.8/0.97). Cumulative incidence of relapse was 34 % after RIC and 8 % after MAC (p = 0.16). Three-year non-relapse mortality (NRM) was 15 % after RIC and 34 % after MAC (p = 0.29). We found that RIC was associated with a lower incidence of acute graft versus host disease (GvHD; II-IV 26 vs. 0 %, p = 0.004). Evaluation of prognostic relevance of the Dynamic International Prognostic Scoring System (DIPSS) score showed a significant better OS in patient with risk score ≤3 versus >3 (after 3 years, 71 vs. 39 %, p = 0.008). While similar OS and DFS were observed with MAC or RIC, the use of RIC resulted in lower incidence of acute GvHD. RIC regimens may be therefore the preferred conditioning approach for allogeneic HCT in patients with MF. PMID:27021303

  13. Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients.

    Science.gov (United States)

    Hogan, William J; Maris, Michael; Storer, Barry; Sandmaier, Brenda M; Maloney, David G; Schoch, H Gary; Woolfrey, Ann E; Shulman, Howard M; Storb, Rainer; McDonald, George B

    2004-01-01

    Liver injury is a frequent, serious complication of allogeneic hematopoietic cell transplantation (HCT) following myeloablative preparative regimens. We sought to determine the frequency and severity of hepatic injury after nonmyeloablative conditioning and its relationship to outcomes. One hundred ninety-three consecutive patients who received 2 Gy total body irradiation with or without fludarabine were evaluated for end points related to liver injury. Patients with diseases treatable by HCT who were ineligible for conventional myeloablative allogeneic HCT because of advanced age and/or comorbid conditions were included. Fifty-one patients (26%) developed hyperbilirubinemia of 68.4 microM (4 mg/dL) or greater, most commonly resulting from cholestasis due to graft-versus-host disease (GVHD) or sepsis. Pretransplantation factors associated with liver dysfunction were a diagnosis of aggressive malignancy (hazard ratio [HR] 1.9; P =.04) and the inclusion of fludarabine in the conditioning regimen (HR 1.8; P =.07). Overall survival at 1 year was superior for patients who had maximal serum bilirubin levels in the normal (78%) or minimally elevated (22.23-66.69 microM [1.3-3.9 mg/dL]) ranges (69%) compared with those in the 68.4 to 117.99 microM (4-6.9 mg/dL; 20%), 119.7 to 169.29 microM (7.0-9.9 mg/dL; 17%), and 171.0 microM (10 mg/dL; 19%) or greater groups. In summary, significant jaundice occurred in 26% of patients and was predominantly due to cholestasis resulting from GVHD and/or sepsis. Aggressive malignancies (mainly advanced disease) and later development of jaundice after transplantation predicted inferior survival. PMID:12969980

  14. Correlation of Pain and Fluoride Concentration in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Voriconazole.

    Science.gov (United States)

    Barajas, Megan R; McCullough, Kristen B; Merten, Julianna A; Dierkhising, Ross A; Bartoo, Gabriel T; Hashmi, Shahrukh K; Hogan, William J; Litzow, Mark R; Patnaik, Mrinal M; Wilson, John W; Wolf, Robert C; Wermers, Robert A

    2016-03-01

    Supportive care guidelines recommend antimold prophylaxis in hematopoietic stem cell transplant (HSCT) recipients deemed to have high risk for invasive fungal infection, leading to long-term use of voriconazole after allogeneic HSCT in patients who remain immunocompromised. Voriconazole has been associated with periostitis, exostoses, and fluoride excess in patients after solid organ transplantation, HSCT, and leukemia therapy. The aims of this study were to describe the frequency and clinical presentation of patients presenting with pain and fluoride excess among allogeneic HSCT patients taking voriconazole, to identify when a plasma fluoride concentration was measured with respect to voriconazole initiation and onset of pain, and to describe the outcomes of patients with fluoride excess in the setting of HSCT. A retrospective review was conducted of all adult allogeneic HSCT patients receiving voriconazole at Mayo Clinic in Rochester, Minnesota, between January 1, 2009 and July 31, 2012. Of 242 patients included, 32 had plasma fluoride measured to explore the etiology of musculoskeletal pain. In 31 patients with fluoride measurement while on voriconazole, 29 (93.5%) had elevated levels. The median plasma fluoride was 11.1 μmol/L (range, 2.4 to 24.7). The median duration of voriconazole was 163 days (range, 2 to 1327). The median time to fluoride measurement was 128 days after voriconazole initiation (range, 28 to 692). At 1 year after the start of voriconazole after HSCT, 15.3% of patients had developed pain associated with voriconazole use and 35.7% developed pain while on voriconazole after 2 years. Of the patients with an elevated fluoride level, 22 discontinued voriconazole; pain resolved or improved in 15, stabilized in 3, and worsened in 4 patients. Ten patients continued voriconazole; pain resolved or improved in 7, was attributable to alternative causes in 2, and undefined in 1. Serum creatinine, estimated glomerular filtration rate, alkaline phosphatase

  15. Refinement of molecular approaches to improve the chance of identification of hematopoietic-restricted minor histocompatibility antigens.

    NARCIS (Netherlands)

    Rijke, B. de; Horssen-Zoetbrood, A. van; Veenbergen, S.; Fredrix, H.; Witte, T.J.M. de; Kemenade, E van de Wiel-van; Dolstra, H.

    2008-01-01

    Minor histocompatibility antigens (mHAgs) constitute the target antigens of the T cell-mediated graft-versus-leukemia response after HLA-identical allogeneic stem cell transplantation (SCT). Several human mHAgs have been identified, but only a few are selectively expressed by hematopoietic cells rep

  16. Prognostic Utility of Routine Chimerism Testing at 2 – 6 Months after Allogeneic Hematopoietic Cell Transplantation

    Science.gov (United States)

    Mossallam, Ghada I.; Kamel, Azza M.; Storer, Barry; Martin, Paul J.

    2009-01-01

    The utility of routine chimerism analysis as a prognostic indicator of subsequent outcomes after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning regimens remains controversial. To address this controversy, routine chimerism test results at 2 – 6 months after HCT with myeloablative conditioning regimens were evaluated for association with subsequent risks of chronic graft versus host disease (GVHD), non-relapse mortality (NRM), relapse and overall mortality. Only 70 (5%) of 1304 patients had <95% donor-derived cells in the marrow. Low donor chimerism in the marrow occurred predominantly among patients with low risk disease as compared to higher risk diseases and was significantly associated with a reduced risk of chronic GVHD. Among 673 patients tested, 164 (24%) had <85% donor-derived T cells in the blood. Low donor T cell chimerism occurred predominantly among patients with low risk disease as compared to higher risk diseases, among those who had conditioning with busulfan as compared to TBI, and among those with lower grades of acute GVHD. Low donor T cell chimerism in the blood was significantly associated with a reduced risk of chronic GVHD, but not with the risks of relapse, NRM or overall mortality. Routine testing of chimerism in the marrow and blood at 2 – 6 months after HCT with myeloablative conditioning regimens may be helpful in documenting engraftment in clinical trials but provides only limited prognostic information in clinical practice. PMID:19203726

  17. Donor-Specific Anti-HLA Antibodies in Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Morin-Zorman, Sarah; Loiseau, Pascale; Taupin, Jean-Luc; Caillat-Zucman, Sophie

    2016-01-01

    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 3–4% 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 and 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.

  18. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia.

    Science.gov (United States)

    Munker, Reinhold; Brazauskas, Ruta; Wang, Hai Lin; de Lima, Marcos; Khoury, Hanna J; Gale, Robert Peter; Maziarz, Richard T; Sandmaier, Brenda M; Weisdorf, Daniel; Saber, Wael

    2016-06-01

    Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival. PMID:26903380

  19. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle; Gormsen, Magdalena; Pedersen, Karen Damgaard; Buchvald, Frederik; Heilmann, Carsten; Nielsen, Kim Gjerum; Mortensen, Jann; Moser, Claus; Sengeløv, Henrik; Müller, Klaus Gottlob

    2015-03-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases. PMID:25498923

  20. Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients.

    Science.gov (United States)

    Mani, S; Rybicki, L; Jagadeesh, D; Mossad, S B

    2016-05-01

    Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P=0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI. PMID:26726944

  1. 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

    2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal......, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for......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 and...

  2. Process of allogeneic hematopoietic cell transplantation decision making for older adults.

    Science.gov (United States)

    Randall, J; Keven, K; Atli, T; Ustun, C

    2016-05-01

    Allogeneic hematopoietic cell transplantation (alloHCT) may be the only curative option for some older adults with hematologic malignancies, and its associated risks of significant morbidity and mortality warrant a clear, informed decision-making process. As older adults have not been transplanted routinely until recent years, younger people have been the prototypical group around whom the current process has developed. Yet, this process is applied to older adults who have different considerations than younger patients when making their transplant decision. Older adults do not have the open-ended lives of younger patients and are entitled to consider how to spend their remaining time. They also possess maturity and experience, and with proper knowledge, they can make informed choices rather than moving forward in the transplant process unaware. Notably, older patients face similar problems with the informed decision-making process in nephrology. Strategies such as providing education about alloHCT gradually and repeatedly during induction, presenting recent knowledge from the literature in plain language, and utilizing a team approach to patient education may help older adults make the best decision about transplant in light of their situation and values. Understanding when and how older adults decide on alloHCT is an important first step to further exploring this problem. PMID:26457910

  3. 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

    2007 in Europe. Forty-five SOT in 40 patients were reported. Fifteen liver, 15 renal, 13 lung, 1 heart and 1 skin transplantations were performed in 28 centers. Overall survival (OS) of patients after SOT was 78% at 5 years (95% confidence interval [CI], 64% to 92%). OS at 5 years was 100% for renal......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 and......, 71% (95% CI, 46% to 96%) for liver and 63% (95% CI, 23% to 100%) for lung transplant recipients. The 2-year-incidence of SOT failure was 20% (95% CI, 4% to 36%) in patients with graft-versus-host disease (GvHD) and 7% (95% CI, 0% to 21%) in patients without GvHD before SOT. The relapse incidence for...

  4. Serial measurements of cardiac biomarkers in patients after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Roziakova Lubica

    2012-02-01

    Full Text Available Abstract Background Previous therapy with anthracyclines (ANT and conditioning regimen followed by hematopoietic stem cell transplantation (HSCT represents a high risk for development of cardiotoxicity. The aim of this study was to assess subclinical myocardial damage after HSCT using echocardiography and cardiac biomarkers - high sensitive cardiac troponin T (hs-cTnT and N-terminal pro-B-type natriuretic peptide (NT-proBNP and to identify patients at risk of developing clinical cardiotoxicity. Patients and methods Thirty-seven patients who were treated with allogeneic HSCT for hematologic diseases at median age of 28 years at time of HSCT were studied. Conditioning regimen included either chemotherapy without total body irradiation (TBI or combination of chemotherapy with TBI. Twenty-nine (78,3% patients were pretreated with ANT therapy. Cardiac biomarkers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before conditioning regimen and 1 month after HSCT by echocardiography. Results The changes in plasma NT-proBNP and hs-cTnT levels during the 30 days following the HSCT were statistically significant (P P Conclusions Elevations in both cardiac biomarkers were found before clinical signs of cardiotoxicity developed. Persistent elevations in NT-pro-BNP and hs-cTnT concentrations simultaneously for a period exceeding 14 days might be used for identification of patients at risk of developing cardiotoxicity and requiring further cardiological follow up.

  5. Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Nomura, Shosaku; Maeda, Yoshinobu; Ishii, Kazuyoshi; Katayama, Yuta; Yagi, Hideo; Fujishima, Naoto; Ota, Shuichi; Moriyama, Masato; Ikezoe, Takayuki; Miyazaki, Yasuhiko; Hayashi, Kunio; Fujita, Shinya; Satake, Atsushi; Ito, Tomoki; Kyo, Taiichi; Tanimoto, Mitsune

    2016-01-01

    Background Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. Materials and methods The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. Conclusion Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. PMID:26848281

  6. Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients.

    Science.gov (United States)

    Yew, P Y; Alachkar, H; Yamaguchi, R; Kiyotani, K; Fang, H; Yap, K L; Liu, H T; Wickrema, A; Artz, A; van Besien, K; Imoto, S; Miyano, S; Bishop, M R; Stock, W; Nakamura, Y

    2015-09-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation. PMID:26052909

  7. Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients

    Directory of Open Access Journals (Sweden)

    Gabriela Soriano Hobbs

    2015-03-01

    Full Text Available Graft versus host disease (GVHD remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT. The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medical comorbidities or with only HLA-mismatched donors to successfully undergo transplantation. Prospective data are needed to further define which groups of patients with AML are most likely to benefit from CD34+ selected grafts. Here we review the history of T-cell depletion in AML, and techniques used. We then summarize the contemporary literature using CD34+ selection in recipients of matched or partially mismatched donors (7/8 or 8/8 HLA-matched, and provide a summary of the risks and benefits of using T-cell depletion.

  8. Impact of Human Herpesvirus-6 Reactivation on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Aoki, Jun; Numata, Ayumi; Yamamoto, Eri; Fujii, Eriko; Tanaka, Masatsugu; Kanamori, Heiwa

    2015-11-01

    Human herpesvirus-6 (HHV-6) is known to reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with development of acute graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the clinical significance of HHV-6 reactivation after allo-HSCT remains unclear. Therefore, we conducted a retrospective analysis to elucidate the impact of HHV-6 reactivation on transplantation outcomes. Of 236 patients who underwent allo-HSCT, 138 (58.5%) developed HHV-6 reactivation and 98 (41.5%) did not. Univariate analysis indicated that at 3 years, patients with HHV-6 reactivation had significantly higher NRM (27.7% versus 13.7%, P = .003) and worse overall survival (42.1% versus 59.0%, P = .008) than those without reactivation. In multivariate analysis, HHV-6 reactivation was associated with higher incidence of acute GVHD (hazard ratio [HR], 1.87; P = .01), cytomegalovirus reactivation (HR, 2.24; P HHV-6 reactivation on acute GVHD was observed only in patients who received myeloablative conditioning (MAC). These results indicate that HHV-6 reactivation was associated with development of acute GVHD, cytomegalovirus reactivation, and NRM. Furthermore, adverse impact of HHV-6 reactivation on transplantation outcomes was prominent in the setting of MAC. PMID:26226409

  9. Reduced-intensity conditioning allogeneic hematopoietic-cell transplantation for older patients with acute myeloid leukemia.

    Science.gov (United States)

    Goyal, Gaurav; Gundabolu, Krishna; Vallabhajosyula, Saraschandra; Silberstein, Peter T; Bhatt, Vijaya Raj

    2016-06-01

    Elderly patients (>60 years) with acute myeloid leukemia have a poor prognosis with a chemotherapy-alone approach. Allogeneic hematopoietic-cell transplantation (HCT) can improve overall survival (OS). However, myeloablative regimens can have unacceptably high transplant-related mortality (TRM) in an unselected group of older patients. Reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning regimens preserve the graft-versus-leukemia effects but reduce TRM. NMA regimens result in minimal cytopenia and may not require stem cell support for restoring hematopoiesis. RIC regimens, intermediate in intensity between NMA and myeloablative regimens, can cause prolonged myelosuppresion and usually require stem cell support. A few retrospective and prospective studies suggest a possibility of lower risk of relapse with myeloablative HCT in fit older patients with lower HCT comorbidity index; however, RIC and NMA HCTs have an important role in less-fit patients and those with significant comorbidities because of lower TRM. Whether early tapering of immunosuppression, monitoring of minimal residual disease, and post-transplant maintenance therapy can improve the outcomes of RIC and NMA HCT in elderly patients will require prospective trials. PMID:27247754

  10. Possible implication of bacterial infection in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Shigeo eFuji

    2014-04-01

    Full Text Available Graft-versus-host disease (GVHD is still one of the major causes of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (HSCT. In the pathogenesis of acute GVHD, it has been established that donor-derived T cells activated in the recipient play a major role in GVHD in initiation and maintenance within an inflammatory cascade. To reduce the risk of GVHD, intensification of GVHD prophylaxis like T cell depletion is effective, but it inevitably increases the risk of infectious diseases and abrogates beneficial graft-versus-leukemia effects. Although various cytokines are considered to play an important role in the pathogenesis of GVHD, GVHD initiation is such a complex process that cannot be prevented by means of single inflammatory cytokine inhibition. Thus, efficient methods to control the whole inflammatory milieu both on cellular and humoral view are needed. In this context, infectious diseases can theoretically contribute to an elevation of inflammatory cytokines after allogeneic HSCT and activation of various subtypes of immune effector cells, which might in summary lead to an aggravation of acute GVHD. The appropriate treatments or prophylaxis of bacterial infection during the early phase after allogeneic HSCT might be beneficial to reduce not only infectious-related but also GVHD-related mortality. Here, we aim to review the literature addressing the interactions of bacterial infections and GVHD after allogeneic HSCT.

  11. Clinical characteristics and risk factors of Intracranial hemorrhage in patients following allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Zhang, Xiao-Hui; Wang, Qian-Ming; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Feng-Rong; Wang, Jing-Zhi; Zhang, Yuan-Yuan; Mo, Xiao-Dong; Chen, Yao; Wang, Yu; Chang, Ying-Jun; Xu, Lan-Ping; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-10-01

    Intracranial hemorrhage (ICH) is one of the most life-threatening neurological complications after allogeneic hematopoietic stem cell transplantation. Although cerebral complications and its causes after allo-HSCT are well documented, assessment of the incidence and risk factors of intracranial hemorrhage following allo-HSCT are less discussed. A nested case-control study was conducted involving 160 subjects drawn from 2169 subjects who underwent HSCT at Peking University People's Hospital between 2004 and 2014. Thirty-two patients (1.5 %) with ICH were identified, and 128 controls were matched for age, gender, transplantation type, and time of transplantation. Intracranial hemorrhage was identified by CT scan and/or MRI by searching hospital records. Among the 32 ICH patients, 27 (82.9 %) developed intraparenchymal hemorrhages (IPH), 2 cases (5.7 %) suffered subdural hematomas (SDH), and 3 cases (8.6 %) had multiple hemorrhage lesions in the brain parenchyma. The median time of appearance for cerebral hemorrhages was 147.5 days. Multivariate analysis showed that systemic infections (hazard ratio 2.882, 95 % confidence interval 1.231-6.746), platelet count (5.894, 1.145-30.339), and fibrinogen levels (3.611, 1.528-8.532) were independent risk factors for intracranial hemorrhage among HSCT patients. The cumulative survival rate in the intracranial hemorrhage and control groups were 43.3 and 74.7 % (P = .001), respectively. Intracranial hemorrhage is associated with high mortality and a decreased overall survival rate. Systemic infections, platelet count, and fibrinogen levels were individual independent risk factors. PMID:27485455

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Anti-thymocyte globulin-induced hyperbilirubinemia in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Ecsedi, Matyas; Schmohl, Jörg; Zeiser, Robert; Drexler, Beatrice; Halter, Jörg; Medinger, Michael; Duyster, Justus; Kanz, Lothar; Passweg, Jakob; Finke, Jürgen; Bethge, Wolfgang; Lengerke, Claudia

    2016-10-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment option for myelofibrosis (MF) despite the emergence of novel targeted therapies. To reduce graft rejection and graft-versus-host disease (GvHD), current allo-HCT protocols often include in vivo T lymphocyte depletion using polyclonal anti-thymocyte globulin (ATG). Shortly after ATG administration, an immediate inflammatory response with fever, chills, and laboratory alterations such as cytopenias, elevation of serum C-reactive protein, bilirubin, and transaminases can develop. Here, we explore whether MF patients, who commonly exhibit extramedullary hematopoiesis in the liver, might be particularly susceptible to ATG-induced liver toxicity. To test this hypothesis, we analyzed 130 control and 94 MF patients from three transplant centers treated with or without ATG during the allo-HCT conditioning regimen. Indeed, hyperbilirubinemia was found in nearly every MF patient treated with ATG (MF-ATG 54/60 = 90 %) as compared to non-ATG treated MF (MF-noATG 15/34 = 44.1 %, p < 0.001) and respectively ATG-treated non-MF patients of the control group (control-ATG, 43/77 = 56 %, p < 0.001). In contrast, transaminases were only inconsistently elevated. Hyperbilirubinemia was in most cases self-limiting and not predictive of increased incidence of non-relapse mortality, hepatic sinusoidal obstruction syndrome (SOS) or liver GvHD. In sum, awareness of this stereotypic bilirubin elevation in MF patients treated with ATG provides a relatively benign explanation for hyperbilirubinemia occurring in these patients during the early transplant. However, attention to drug levels of biliary excreted drugs is warranted, since altered bile flow may influence their clearance and enhance toxicity (e.g., busulfan, antifungal agents). PMID:27480090

  14. Separating graft-versus-leukemia from graft-versus-host disease in allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Li, Jian-Ming; Giver, Cynthia R.; Lu, Ying; Hossain, Mohammad S.; Akhtari, Mojtaba; Waller, Edmund K.

    2009-01-01

    Routine methods to maximize the graft-versus-leukemia (GvL) activity of allogeneic hematopoietic stem cell transplantation (HSCT) without the detrimental effects of graft-versus-host disease (GvHD) are lacking. Depletion or inhibition of alloreactive T cells is partially effective in preventing GvHD, but usually leads to decreased GvL activity. The current model for the pathophysiology of acute GvHD describes a series of immune pathways that lead to activation of donor T cells and inflammator...

  15. Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.

    Science.gov (United States)

    Chen, Chen; Su, Yingjun; Chen, Jianwu; Song, Yajuan; Zhuang, Ran; Xiao, Bo; Guo, Shuzhong

    2016-07-01

    For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period. PMID:27090963

  16. Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD.

    Science.gov (United States)

    Labouré, Gaëlle; Dulucq, Stéphanie; Labopin, Myriam; Tabrizi, Reza; Guérin, Estelle; Pigneux, Arnaud; Lafarge, Xavier; Leguay, Thibaut; Bouabdallah, Krimo; Dilhuydy, Marie-Sarah; Duclos, Cédric; Lascaux, Axelle; Marit, Gérald; Mahon, François-Xavier; Boiron, Jean-Michel; Milpied, Noël; Vigouroux, Stéphane

    2012-12-01

    To investigate the role of reduced-intensity allogeneic (RIC-allo) stem cell transplant (SCT) as postremission therapy in adult intermediate-risk patients with acute myelogenous leukemia (AML) with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD, we conducted a single-center retrospective study between January 2001 and December 2010. Sixty-six patients were included: 37 treated with RIC-alloSCT and 29 with nonallogeneic SCT therapies. Both groups were comparable concerning age, WBC count at diagnosis, gender, karyotype, genotype, and number of courses of chemotherapy to reach complete remission (CR1). Median follow-up after CR1 was 37 months (range, 11-112 months) and 48 months (range, 9-83 months) in the allo and no-allo groups, respectively. In the allo versus no-allo groups, the 3-year cumulative incidence of relapse (CIR) rates were 25% ± 8% versus 61% ± 9%; P = .005. The 3-year nonrelapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS) were 22% ± 7% versus 4% ± 4% (P = .005), 52% ± 9% versus 44% ± 10% (P = .75), and 53% ± 9% versus 35% ± 9% (P = .28), respectively. Multivariate analysis indicated that CIR was reduced by allo (hazard ratio [HR], 0.32; P = .01). A landmark analysis performed at day 185 after CR1 confirmed a lower CIR after allo. RIC-allo reduces the risk of relapse, suggesting a potent graft-versus-leukemia (GVL) effect in these patients at a high risk of relapse. PMID:22766221

  17. Quantitative chimerism kinetics in relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    QIN Xiao-ying; WANG Jing-zhi; ZHANG Xiao-hui; LI Jin-lan; LI Ling-di; LIU Kai-yan; HUANG Xiao-jun; LI Guo-xuan; QIN Ya-zhen; WANG Yu; WANG Feng-rong; LIU Dai-hong; XU Lan-ping; CHEN Huan; HAN Wei

    2012-01-01

    Background Chimerism analysis is an important tool for the surveillance of post-transplant engraftment.It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease.Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).Methods A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient.Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally.The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.Results Twenty-one patients experienced leukemia relapse at a median of 135 days (range,30-720 days) after transplantation.High recipient chimerism in BM was found in all patients at relapse,and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse.With 0.5% recipient DNA as the cut-off,median time between the detection of increased recipient chimerism and relapse was 45 days (range,0-120 days),with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse.Median percentage of recipient DNA in 20 stable remission patients was 0.28%,0.04%,0.05%,0.05%,0.08%,and 0.05% at 1,2,3,6,9,and 12 months,respectively,after transplantation.This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination.The recipient chimerisms in BM were significantly higher than those in PB at relapse (P=0.001).Conclusions This SP-based RT-PCR essay is a reliable method for chimerism analysis.Chimerism kinetics in BM can be used as a marker of impending leukemia relapse,especially when no other specific marker is available.Based on our findings

  18. 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.; van Biezen, A.; Brand, R.; de Witte, T.; 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 resol

  19. The Incidence and Severity of Oral Mucositis among Allogeneic Hematopoietic Stem Cell Transplantation Patients: A Systematic Review.

    Science.gov (United States)

    Chaudhry, Hafsa M; Bruce, Alison J; Wolf, Robert C; Litzow, Mark R; Hogan, William J; Patnaik, Mrinal S; Kremers, Walter K; Phillips, Gordon L; Hashmi, Shahrukh K

    2016-04-01

    Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria

  20. Bortezomib for the prevention and treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Al-Homsi, Ahmad Samer; Feng, Yuxin; Duffner, Ulrich; Al Malki, Monzr M; Goodyke, Austin; Cole, Kelli; Muilenburg, Marlee; Abdel-Mageed, Aly

    2016-09-01

    Allogeneic hematopoietic stem cell transplantation is the standard treatment for a variety of benign and malignant conditions. However, graft-versus-host disease (GvHD) continues to present a major barrier to the success and wide applicability of this procedure. Although current GvHD prevention and treatment regimens exclusively target T cells, bortezomib, a reversible proteasome inhibitor, possesses unique immune regulatory activities that span a wide variety of cellular processes of T and dendritic cells essential for the development of GvHD. Herein, we review the current understanding of the effects of bortezomib in vitro and in animal models and summarize the clinical data relevant to its use in the prevention and treatment of GvHD. We conclude with an outline of the remaining challenges and opportunities to optimize bortezomib's potential role in this setting. PMID:27224851

  1. 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; Masmas, TN; Nielsen, Morten; Thiim, Martin Hansen; Garred, P; Stryhn, A; Lund, Ole; Buus, S; Vindelov, L

    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...... HCT (matched related donor, n=70; matched unrelated donor, n=56) for hematologic malignancies. Initially, the cohort was genotyped for 53 nsSNPs in 11 known miHA source proteins. Twenty-three nsSNPs within six miHA source proteins showed variation in the graft-versus-host (GVH) direction. No...... mortality (39% vs 10%, P=0.0094, adjusted HR 4.6, P=0.0038). No association between number of predicted miHAs and any other clinical outcome parameters was observed. Collectively, our data suggest that the clinical outcome of HCT is not affected by disparate nsSNPs per se, but rather by the HLA...

  2. 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

  3. 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

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

    International Nuclear Information System (INIS)

    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

  5. Human Biomarker Discovery and Predictive Models for Disease Progression for Idiopathic Pneumonia Syndrome Following Allogeneic Stem Cell Transplantation*

    OpenAIRE

    Schlatzer, Daniela M.; Dazard, Jean-Eudes; Ewing, Rob M.; Ilchenko, Serguei; Tomcheko, Sara E.; Eid, Saada; Ho, Vincent; Yanik, Greg; Chance, Mark R.; Cooke, Kenneth R.

    2012-01-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative therapy for many malignant and nonmalignant conditions. Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication that limits successful outcomes. Preclinical models suggest that IPS represents an immune mediated attack on the lung involving elements of both the adaptive and the innate immune system. However, the etiology of IPS in humans is less well understood. To explore the disease pathway and uncov...

  6. Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

    Directory of Open Access Journals (Sweden)

    Gustavo Machado Teixeira

    Full Text Available Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI has enabled better prediction of transplant-related mortality (TRM in allogeneic hematopoietic stem cell transplants (AHSCT, data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27, in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM and peripheral blood stem cells (PBSC as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years; HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3 in this Brazilian population might justify these results.

  7. Optimal graft source for allogeneic hematopoietic stem cell transplant: bone marrow or peripheral blood?

    Science.gov (United States)

    Adhikari, Janak; Sharma, Priyadarshani; Bhatt, Vijaya Raj

    2016-08-01

    Peripheral blood (PB), compared with bone marrow graft, has higher stem cell content, leads to faster engraftment and is more convenient for collection. Consequently, the use of PB graft has significantly increased in recent years. Although the use of PB graft is acceptable or even preferred to bone marrow graft in matched related donor allogeneic transplant due to a possibility of improved survival, PB graft increases the risk of chronic graft-versus-host disease and associated long-term toxicities in the setting of matched unrelated donor allogeneic transplant. In haploidentical transplant, mitigation of graft-versus-host disease with the use of post-transplant cyclophosphamide is a hypothesis-generating possibility; however, available studies have significant limitations to draw any definite conclusion. PMID:27168462

  8. Voriconazole-Induced Phototoxicity Masquerading as Chronic Graft-versus-Host Disease of the Skin in Allogeneic Hematopoietic Cell Transplant Recipients

    OpenAIRE

    Patel, Asha R.; Turner, Maria L.; Baird, Kristin; Gea-Banacloche, Juan; Mitchell, Sandra; Pavletic, Steven Z.; Wise, Barbara; Cowen, Edward W.

    2009-01-01

    Systemic fungal infections pose a significant risk to patients following allogeneic hematopoietic cell transplantation (alloHCT). Voriconazole (Vfend®, Pfizer) is an oral second-generation triazole antifungal agent that offers broad spectrum of coverage against fungal species and is frequently utilized in the post-HCT setting. Herein, we describe five patients who were initially believed to be experiencing a flare of cutaneous chronic graft-versus-host disease (cGvHD), but who were actually e...

  9. Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients

    OpenAIRE

    Bow, Eric J; Vanness, David J.; Slavin, Monica; Cordonnier, Catherine; Cornely, Oliver A.; Marks, David I.; Pagliuca, Antonio; Solano, Carlos; Cragin, Lael; Shaul, Alissa J; Sorensen, Sonja; Chambers, Richard; Kantecki, Michal; Weinstein, David; Schlamm, Haran

    2015-01-01

    Background Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making. Methods Randomized controlled trials (RCTs) of fluconazole, itracona...

  10. Highly Elevated Serum Hepcidin in Patients with Acute Myeloid Leukemia prior to and after Allogeneic Hematopoietic Cell Transplantation: Does This Protect from Excessive Parenchymal Iron Loading?

    OpenAIRE

    Haifa Kathrin Al-Ali; Dietger Niederwieser; Marianne Hehme; Daniel Teupser; Sabine Leiblein; Uwe Gerd Liebert; Mark Westerman; Rainer Krahl; Ann-Kathrin Eisfeld

    2011-01-01

    Hepcidin is upregulated by inflammation and iron. Inherited (HFE genotype) and treatment-related factors (blood units (BU), Iron overload) affecting hepcidin (measured by C-ELISA) were studied in 42 consecutive patients with AML prior to and after allogeneic hematopoietic cell transplantation (HCT). Results. Elevated serum ferritin pre- and post-HCT was present in all patients. Median hepcidin pre- and post-HCT of 358 and 398 ng/mL, respectively, were elevated compared to controls (median 52 ...

  11. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  12. Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience.

    Science.gov (United States)

    Verdeguer, A; de Heredia, C D; González, M; Martínez, A M; Fernández-Navarro, J M; Pérez-Hurtado, J M; Badell, I; Gómez, P; González, M E; Muñoz, A; Díaz, M A

    2011-01-01

    We studied surveillance, incidence and outcome of viral infections in children undergoing allogeneic hematopoietic cell transplantation (HCT) in the main pediatric transplant units in Spain. We prospectively collected data from first year post-HCT in every consecutive allogeneic HCT performed during 3 years (N = 215): first HCT = 188 and second HCT = 27; median age = 6.6 years (0.1-20.7). Most patients had acute leukemia (N = 137) and 135 recipients (63%) were CMV seropositive. A total of 46 patients underwent cord blood transplant, 133 patients underwent HCT from alternative donors (62%) and 101 patients received anti-thymocyte globulin. Observational time was completed in 137 patients, whereas the remaining 78 died after a median survival time of 99 days (3-352). CMV was monitored in all patients; adenovirus (ADV) and human herpesvirus 6 (HHV-6) were monitored in 101 and 33 patients, respectively. We found 145 viral infections in 103 patients: CMV (n = 42), ADV (n = 32), HHV-6 (n = 7), polyomavirus (n = 20), EBV (n = 6), VZV (n=17) and others (n = 8). CMV infection was significantly higher in seropositive patients (25 vs 7%) (P = 0.02). Extensive chronic GVHD (cGVHD) was significantly associated with an increased rate of viral infections (12 of 16 patients with cGVHD had infections vs 91 of 199 without GVHD) (P = 0.035). In total, 10 patients (4.6%) died of viral infections (CMV = 5, ADV = 3, respiratory = 2). We found a high incidence of viral infection, but mortality was low. PMID:20228849

  13. Association of Distance from Transplantation Center and Place of Residence on Outcomes after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Khera, Nandita; Gooley, Ted; Flowers, Mary E D; Sandmaier, Brenda M; Loberiza, Fausto; Lee, Stephanie J; Appelbaum, Frederick

    2016-07-01

    Regionalization of specialized health services can deliver high-quality care but may have an adverse impact on access and outcomes because of distance from the regional centers. In the case of hematopoietic cell transplantation (HCT), the effect of increased distance between the transplantation center and the rural/urban residence is unclear because of conflicting results from the existing studies. We examined the association between distance from primary residence to the transplantation center and rural versus urban residence with clinical outcomes after allogeneic HCT in a large cohort of patients. Overall mortality (OM), nonrelapse mortality (NRM), and relapse in all patients and those who survived for 200 days after HCT were assessed in 2849 patients who received their first allogeneic HCT between 2000 and 2010 at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance. Median distance from FHCRC was 263 miles (range, 0 to 2740 miles) and 83% of patients were urban residents. The association between distance and the hazard of OM varied according to conditioning intensity: myeloablative (MA) versus nonmyeloablative (NMA). Among MA patients, there was no evidence of an increased risk of mortality with increased distance, but for NMA patients, the results did show a suggestion of increased risk of mortality for some distances, although globally the difference was not statistically significant. In the subgroup of patients who survived 200 days, there was no evidence that the risks of OM, relapse, or NRM were increased with increasing distance. We did not find any association between longer distance from transplantation center and urban/rural residence and outcomes after MA HCT. In patients undergoing NMA transplantations, this relationship and how it is influenced by factors such as age, payers, and comorbidities needs to be further investigated. PMID:27013013

  14. Apoptosis Susceptibility Prolongs the Lack of Memory B Cells in Acute Leukemic Patients After Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mensen, Angela; Oh, Youngseong; Becker, Sonya C; Hemmati, Philipp G; Jehn, Christian; Westermann, Jörg; Szyska, Martin; Göldner, Henning; Dörken, Bernd; Scheibenbogen, Carmen; Arnold, Renate; Na, Il-Kang

    2015-11-01

    Long-term survival after allogeneic hematopoietic stem cell transplantation requires intact immunosurveillance, which is hampered by lymphoid organ damage associated with conditioning therapy, graft-versus-host disease, and immunosuppression. Our study aimed to identify the mechanisms contributing to sustained low memory B cell numbers after transplantation. Peripheral B and T cell subset recovery and functional marker expression were investigated in 35 acute leukemic patients up to 1 year after transplantation. Apoptosis of B cells after CD40/TLR-9, CD40/BCR, and CD40/BCR/TLR-9-dependent stimulation and drug efflux capacity were analyzed. One half of the patients suffered from infections after day 180. All patients had strongly diminished CD27(+) memory B cells despite already normalized total B cell numbers and fully recovered CD27(-)IgD(-) memory B cells, putatively of extra-follicular origin. Circulating memory follicular helper T cells were reduced in the majority of patients as well. Naïve B cells exhibited a decreased expression of CXCR5, which mediates follicular B cell entry. Additionally, a lower HLA-DR expression was found on naïve B cells, impairing antigen presentation. Upon CD40/TLR-9-dependent activation, B cells underwent significantly increased apoptosis paralleled by an aberrant up-regulation of Fas-L on activated T cells and Fas on resting B cells. Significantly increased B cell apoptosis was also observed after CD40/BCR and CD40/BCR/TLR-9-dependent activation. Drug efflux capacity of naïve B cells was diminished in cyclosporin A-treated patients, additionally contributing to an apoptosis-prone phenotype. We conclude that B cell survival and migration and T cell communication defects are contributing candidates for an impaired germinal center formation of memory B cells after allogeneic hematopoietic stem cell transplantation. Follow-up studies should evaluate effectiveness of revaccinations on the cellular level and should

  15. Regulatory T-cell immunotherapy for allogeneic hematopoietic stem-cell transplantation

    OpenAIRE

    Horch, Matthew; Nguyen, Vu H

    2012-01-01

    From mouse studies to recently published clinical trials, evidence has accumulated on the potential use of regulatory T cells (Treg) in preventing and treating graft-versus-host disease following hematopoietic-cell transplantation (HCT). However, controversies remain as to the phenotype and stability of various Treg subsets and their respective roles in vivo, the requirement of antigen-specificity of Treg to reduce promiscuous suppression, and the molecular mechanisms by which Treg suppress, ...

  16. The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Mørup, Anne Mette; Kornblit, Brian; Johansen, Julia S; Masmas, Tania Nicole; Madsen, Hans O; Vindeløv, Lars; Garred, Peter

    2011-01-01

    plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had...... function as a biomarker for relapse risk and treatment-related toxicity, and possibly as a tool complementing clinical risk scores such as the HCT comorbidity index....

  17. The prognostic value of YKL-40 concentrations in nonmyeloablative conditioning allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Mørup, Anne Mette; Kornblit, Brian; Johansen, Julia S; Masmas, Tania Nicole; Madsen, Hans O; Vindeløv, Lars; Garred, Peter

    2011-01-01

    plasma YKL-40 concentrations as prognostic biomarkers in a cohort of 149 patients treated with hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning for hematologic malignancies. Recipients with pretransplant YKL-40 concentrations above the age-adjusted 95th percentile (high) had...... could function as a biomarker for relapse risk and treatment-related toxicity, and possibly as a tool complementing clinical risk scores such as the HCT comorbidity index....

  18. Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: A prospective sibling donor versus no-donor comparison

    OpenAIRE

    Cornelissen, Jan; Holt, Bronno; Verhoef, Gregor; Veer, Mars; Oers, Marinus; Ossenkoppele, Gert; Sonneveld, Pieter; Maertens, Johan; Marwijk Kooy, Marinus; Schaafsma, Martijn; Wijermans, Pierre; Biesma, Douwe; Wittebol, Shulamit; Voogt, Paul; Baars, Joke

    2009-01-01

    textabstractWhile commonly accepted in poor-risk acute lymphoblastic leukemia (ALL), the role of allogeneic hematopoietic stem cell transplantation (allo-SCT) is still disputed in adult patients with standard-risk ALL. We evaluated outcome of patients with ALL in first complete remission (CR1), according to a sibling donor versus no-donor comparison. Eligible patients (433) were entered in 2 consecutive, prospective studies, of whom 288 (67%) were younger than 55 years, in CR1, and eligible t...

  19. Very Long Term Stability of Mixed Chimerism after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Emmanuel Levrat

    2015-01-01

    Full Text Available The objective of this study is to analyze the evolution of chimerism of all patients transplanted for hematologic malignancies in our unit during a 20-year period, alive without relapse at 1 year after allogeneic hematopoietic stem cell transplantation (HSCT. Chimerism was tested using short tandem repeat polymorphisms after separation into mononuclear cells and granulocytes by Ficoll density gradient centrifugation. Of 155 patients studied, 89 had full chimerism (FC, 36 mononuclear cells mixed chimerism (MNC-MC, and 30 granulocytic MC with or without mononuclear cells MC (Gran-MC. Survival was significantly better in MNC-MC than in Gran-MC patients, with FC patients being intermediate. There was more disease relapse in the Gran-MC group but not in the MNC-MC group as compared to FC. MC was stable up to 21 years in the MNC-MC group and up to 19 years in the Gran-MC group. Of MC patients alive at 10 years, MC persisted in 83% in the MNC-MC and 57% in the Gran-MC groups. In conclusion, mixed chimerism may remain stable over a very long time period. In survivors without relapse at 1 year after HSCT, determining lineage specific chimerism may be useful as outcome differs, MNC-MC being associated with better outcome than Gran-MC.

  20. Risk factors for vancomycin-resistant enterococcus bacteremia and its influence on survival after allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Tavadze, M; Rybicki, L; Mossad, S; Avery, R; Yurch, M; Pohlman, B; Duong, H; Dean, R; Hill, B; Andresen, S; Hanna, R; Majhail, N; Copelan, E; Bolwell, B; Kalaycio, M; Sobecks, R

    2014-10-01

    Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted. PMID:25111516

  1. Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation.

    Science.gov (United States)

    Liu, X; Yue, Z; Yu, J; Daguindau, E; Kushekhar, K; Zhang, Q; Ogata, Y; Gafken, P R; Inamoto, Y; Gracon, A; Wilkes, D S; Hansen, J A; Lee, S J; Chen, J Y; Paczesny, S

    2016-08-01

    Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (≥1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS. PMID:26887344

  2. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  3. Fatal human metapneumovirus and influenza B virus coinfection in an allogeneic hematopoietic stem cell transplant recipient.

    Science.gov (United States)

    Ghattas, C; Mossad, S B

    2012-10-01

    Human metapneumovirus (hMPV) infection can occur in all age groups with significant morbidity and mortality. Coinfection with influenza virus occurs mainly with influenza type A and all reported cases recovered completely. We report the case of a 61-year-old man who had hematopoietic stem cell transplant for myelodysplastic syndrome. He was admitted to hospital for septic shock and neutropenia, and blood culture was positive for Pseudomonas aeruginosa. He rapidly developed respiratory failure and required ventilator support. His respiratory culture grew P. aeruginosa and hMPV. His course was complicated by persistent shock requiring vasopressor support, and repeat nasopharyngeal swab was positive for influenza type B and hMPV. His condition rapidly deteriorated, his family elected comfort care, and the patient died shortly thereafter. Coinfection with hMPV and influenza virus type B may have a poor outcome and can be fatal, especially in immunocompromised patients. PMID:22823898

  4. A fast and simple approach for the simultaneous detection of hematopoietic chimerism, NPM1, and FLT3-ITD mutations after allogeneic stem cell transplantation.

    Science.gov (United States)

    Waterhouse, Miguel; Bertz, Hartmut; Finke, Juergen

    2014-02-01

    Hematopoietic chimerism can be used as a tool for patient management after allogeneic hematopoietic stem cell transplantation (HSCT). An increase in the proportion of recipient cells after transplantation is strongly associated with relapse in chronic myeloid leukemia. However, in acute myeloid leukemia (AML) the significance of increasing mixed chimerism (MC) as a predictive marker for relapse is less clear. Several mutations frequently found in AML have been employed for minimal residual disease detection and relapse prediction. Therefore, a combined analysis of hematopoietic chimerism and of the molecular aberrations found in AML could be used to improve MC characterization. We developed a multiplex PCR for use in the simultaneous detection of hematopoietic chimerism and mutations in nucleophosmin (NPM1) and fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD). A total of 303 samples from 20 AML patients were analyzed after HSCT. The microsatellite markers used for hematopoietic chimerism detection were D1S80, D7S1517, D4S2366, THO1, and SE33. A total of 149 samples from 18 patients showed MC with a mean detection time of 9.7 months. From the 18 patients with MC, in 6 of the patients, no FLT3-ITD or NPM1 mutation was found at any time point tested, and these patients remained in complete hematological remission. In 12 patients with MC, FLT3-ITD and NPM1 mutations were found, and these patients showed signs of hematological relapse. Our combined analysis of NPM1/FLT3-ITD mutations and hematopoietic chimerism improved the characterization of patients with MC after HSCT. The present approach may be further expanded by combining additional mutations found in AML with hematopoietic chimerism detection. PMID:23907410

  5. Favorable outcomes in patients surviving 5 or more years after allogeneic hematopoietic stem cell transplantation for hematologic malignancies.

    Science.gov (United States)

    Le, Robert Quan; Bevans, Margaret; Savani, Bipin N; Mitchell, Sandra A; Stringaris, Kate; Koklanaris, Eleftheria; Barrett, A John

    2010-08-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for some hematologic malignancies. As the overall number of survivors continues to increase, studies systematically examining outcomes in long-term survivors are needed. We studied the clinical and quality-of-life outcomes in HSCT recipients surviving 5 or more years from HSCT. Since 1993, 262 patients with hematologic malignancies received a T cell-depleted myeloablative HSCT from an HLA-identical sibling at a single center. Ninety-two survived beyond 5 years from HSCT (median follow-up 9.4 years, range: 5.1-15.3). Median age at transplantation was 35 years (range: 10-56). Twenty-two (24%) received a bone marrow transplant, and 70 (76%) received a peripheral blood HSCT. Of the 92 survivors, 60 completed quality-of-life measures. The main outcomes examined were chronic graft-versus-host-disease, disease relapse, survival, health-related quality-of-life (HRQL) (Functional Assessment of Cancer Therapy-General), physical and mental health (SF-36), and symptom experience (Rotterdam Symptom Checklist). Seventy-five (82%) of 92 survivors no longer required systemic immunosuppressive treatment. Four (4.3%) relapsed with leukemia at a median of 8.5 years (range: 6.2-14.0) after HSCT. Four (4.3%) died between 7.4 and 13.4 years post-HSCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Most survivors beyond 5 years had an excellent performance status with no difference in physical and mental health and higher HRQL scores (P = .02) compared with population norms. Although physical and psychologic symptom distress was low, those with higher symptom distress experienced inferior HRQL. These results show that 5 or more years after T cell-depleted HSCT for hematologic malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent HRQL. PMID:20302959

  6. Mobilization of hematopoietic progenitor cells from allogeneic healthy donors using a new biosimilar G-CSF (Zarzio®).

    Science.gov (United States)

    Antelo, María Luisa; Zabalza, Amaya; Sánchez Antón, María Piva; Zalba, Saioa; Aznar, Mariví; Mansilla, Cristina; Ramírez, Natalia; Olavarría, Eduardo

    2016-02-01

    Peripheral blood progenitor cells (PBPCs) have become the major source of hematopoietic progenitor cells for allogeneic transplantation. In February 2008, Zarzio® was approved by the European Medicine Agency for PBPCs mobilization, but this authorization was not based in trials analyzing safety and efficacy for PBPCs mobilization. Since August 2011, Zarzio® has been used at our institution for PBPCs mobilization. In total 36 healthy family donors underwent PBPCs mobilization, 18 with Neupogen® and 18 with Zarzio®. Donor characteristics were equivalent between groups, and no severe adverse effects were registered in the Zarzio® group. The number of CD34 cells collected/Kg recipient body weight was 6.7 × 10(6) (3.8-11.1) in the Zarzio® group versus 8.4 × 10(6) (5.6-16.6) in the Neupogen® group (P = 0.04). We collected the minimal target cell dose (2 × 10(6) /kg) in all donors from each group and no significant differences were found in the collection of the optimal cell dose (5 × 10(6) /kg) between groups, although 3/18 (16.6%) donors that received Zarzio® failed to mobilize the optimal cell dose compared with 0% in the Neupogen® group. A total of 35 patients proceeded to transplantation (17 in the Zarzio® and 18 in the Neupogen® groups, respectively). Platelet and neutrophil median time to engraftment was comparable between the two groups. Our retrospective study supports the conclusion that Zarzio® mobilization of PBPCs in healthy donors is safe but perhaps not as effective as the reference Neupogen. However, more prospective trials are required to definitively asses the safety and efficacy of G-CSF biosimilars for PBPCs mobilization in healthy donors. PMID:26011178

  7. Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Aldoss, Ibrahim; Tsai, Ni-Chun; Slovak, Marilyn L; Palmer, Joycelynne; Alvarnas, Joseph; Marcucci, Guido; Forman, Stephen J; Pullarkat, Vinod

    2016-07-01

    The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an independent predictor of outcomes in alloHCT performed to treat adult ALL. PMID:27044907

  8. Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

    Directory of Open Access Journals (Sweden)

    Hyun O Kim

    2013-01-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT. Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. &lt;b&gt;Methods:&lt;/b&gt; The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK cell recovery. The impact of preand post-transplant variables, including diagnosis of Epstein-Barr virus (EBV DNAemia posttransplant,on lymphocyte recovery was evaluated. &lt;b&gt;Results:&lt;/b&gt; The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells,and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant. &lt;b&gt;Conclusion:&lt;/b&gt; In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.

  9. Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors.

    Science.gov (United States)

    Anur, P; Friedman, D N; Sklar, C; Oeffinger, K; Castiel, M; Kearney, J; Singh, B; Prockop, S E; Kernan, N A; Scaradavou, A; Kobos, R; Curran, K; Ruggiero, J; Zakak, N; O'Reilly, R J; Boulad, F

    2016-07-01

    Hematopoietic stem cell transplantation (HSCT) is curative for hematological manifestations of Fanconi anemia (FA). We performed a retrospective analysis of 22 patients with FA and aplastic anemia, myelodysplastic syndrome or acute myelogenous leukemia who underwent a HSCT at Memorial Sloan Kettering Cancer Center and survived at least 1 year post HSCT. Patients underwent either a TBI- (N=18) or busulfan- (N=4) based cytoreduction followed by T-cell-depleted transplants from alternative donors. Twenty patients were alive at time of the study with a 5- and 10-year overall survival of 100 and 84% and no evidence of chronic GvHD. Among the 18 patients receiving a TBI-based regimen, 11 (61%) had persistent hemochromatosis, 4 (22%) developed hypothyroidism, 7 (39%) had insulin resistance and 5 (27%) developed hypertriglyceridemia after transplant. Eleven of 16 evaluable patients (68%), receiving TBI, developed gonadal dysfunction. Two patients who received a TBI-based regimen died of squamous cell carcinoma. One patient developed hemochromatosis, hypothyroidism and gonadal dysfunction after busulfan-based cytoreduction. TBI appears to be a risk factor for malignant and endocrine late effects in the FA host. Multidisciplinary follow-up of patients with FA (including cancer screening) is essential for early detection and management of late complications, and improving long-term outcomes. PMID:26999465

  10. Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations.

    Science.gov (United States)

    Hamilton, Betty Ky; Visconte, Valeria; Jia, Xuefei; Tabarroki, Ali; Makishima, Hideki; Hasrouni, Edy; Abounader, Donna; Kalaycio, Matt; Sekeres, Mikkael A; Sobecks, Ronald; Duong Liu, Hien; Bolwell, Brian; Maciejewski, Jaroslaw P; Copelan, Edward; Tiu, Ramon V

    2016-06-01

    Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing. Median time of follow up was 24 months (range 0.46-110). SRSF2 mutations were detected in 11 (10%) patients and U2AF1 in 3 (3%) patients. There were no significant differences in baseline characteristics between mutated and wild-type (WT) patients. Patients carrying SRSF2 and U2AF1 mutations had similar overall survival (P = 0.84), relapse mortality (P = 0.50), and non-relapse mortality (P = 0.72) compared to WT patients. However, taking into account disease status and cytogenetics in a subset of AML patients, SRSF2 and U2AF1 mutations were associated with worse survival (HR 3.71, P = 0.035). Am. J. Hematol. 91:406-409, 2016. © 2016 Wiley Periodicals, Inc. PMID:26799334

  11. 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...... score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS...

  12. FDG PET/CT in Acute Tumefactive Multiple Sclerosis Occurring in a Case of Chronic Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Dong, Aisheng; Gao, Mingjun; Wang, Yang; Gao, Lei; Zuo, Changjing

    2016-09-01

    Tumefactive multiple sclerosis refers to the presentation of large demyelinating lesions (≥2 cm in diameter) mimicking brain tumors clinically and radiologically. We present the MRI and FDG PET/CT findings in a case with tumefactive multiple sclerosis, who had chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Head MRI showed 7 cerebral lesions with incomplete ring enhancement. All but one lesion had size more than 2 cm. All these demyelinating lesions showed increased uptake at the rims of the lesions with central hypometabolism. Stereotactic brain biopsy of the right frontal lesion revealed extensive macrophage and lymphocyte infiltration. PMID:26909714

  13. IFN-γ promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation

    OpenAIRE

    Yang, Yanping; Wang, Hui; Yu, Hui; Yeap, Beow Yong; Liang, Tingting; Wang, Guanjun; Cheng, Tao; Yang, Yong-Guang

    2011-01-01

    The ability of IFN-γ to enhance graft-versus-leukemia (GVL) activity without direct interaction with leukemia cells was examined by comparing GVL effects against IFN-γ receptor-deficient (GRKO) leukemia between wild-type (WT) and IFN-γ–deficient (GKO) allogeneic hematopoietic cell transplantation (allo-HCT). We established a primary IFN-γ–unresponsive T-cell leukemia model using virally-transduced GRKO B6 mouse bone marrow cells overexpressing Notch1. We first assessed GVL effects in lethally...

  14. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk

  15. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hyun [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Tsai, Nicole [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Schultheiss, Timothy E. [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Liu, An [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen J. [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States)

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  16. The Impact of HLA-E Polymorphisms in Graft-versus-Host Disease following HLA-E Matched Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Ehteramolsadat Hosseini

    2012-03-01

    Full Text Available The  non-classical MHC  class-I mainly involves in the  regulation of  innate  immune responses where HLA-E  plays a significant role in the cell identification by natural killer cells. HLA-E is a main regulatory ligand for natural killer cells and given the importance of these effector cells in hematopoietic stem cell transplantation, we investigated the effect of HLA-E polymorphisms on post-hematopoietic stem cell transplantation outcomes.The study group included 56 donor-patient pairs with underlying malignant hematological disorders undergoing HLA-E  matched allogeneic hematopoietic stem cell transplantation. They were genotyped for HLA-E locus using a sequence specific primer-polymerase chain reaction. The  median follow-up was 20.6 months  (range 0.2-114.8 and  the  parameters assessed were acute and chronic graft-versus-host disease and overall survival.We showed a lower frequency of acute graft-versus-host disease (grade II or more; p=0.02and chronic graft-versus-host disease (extensive; p=0.04 in the patients with HLA- E*0103/0103 genotype compared to other genotypes of HLA-E. There was also an association between HLA-E*0103/0103 and improved overall survival (p=0.001.Conclusively, our  results  suggest a  protective  role  for  HLA-E*0103/0103  genotypeagainst acute graft-versus-host disease (grade II or more and chronic graft-versus-host disease (extensive as well as an association between this genotype and a better overall survival after HLA-E matched allogeneic hematopoietic stem cell transplantation.

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

    Directory of Open Access Journals (Sweden)

    Ye. V. Kuzmich

    2015-01-01

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

  18. Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Okamura Hiroshi

    2011-04-01

    Full Text Available Abstract Background There has been insufficient examination of the factors affecting long-term survival of more than 5 years in patients with leukemia that is not in remission at transplantation. Method We retrospectively analyzed leukemia not in remission at allogeneic hematopoietic cell transplantation (allo-HCT performed at our institution between January 1999 and July 2009. Forty-two patients with a median age of 39 years received intensified conditioning (n = 9, standard (n = 12 or reduced-intensity conditioning (n = 21 for allo-HCT. Fourteen patients received individual chemotherapy for cytoreduction during the three weeks prior to reduced-intensity conditioning. Diagnoses comprised acute leukemia (n = 29, chronic myeloid leukemia-accelerated phase (n = 2, myelodysplastic syndrome/acute myeloid leukemia (MDS/AML (n = 10 and plasma cell leukemia (n = 1. In those with acute leukemia, cytogenetic abnormalities were intermediate (44% or poor (56%. The median number of blast cells in bone marrow (BM was 26.0% (range; 0.2-100 before the start of chemotherapy for allo-HCT. Six patients had leukemic involvement of the central nervous system. Stem cell sources were related BM (7%, related peripheral blood (31%, unrelated BM (48% and unrelated cord blood (CB (14%. Results Engraftment was achieved in 33 (79% of 42 patients. Median time to engraftment was 17 days (range: 9-32. At five years, the cumulative probabilities of acute graft-versus-host disease (GVHD and chronic GVHD were 63% and 37%, respectively. With a median follow-up of 85 months for surviving patients, the five-year Kaplan-Meier estimates of leukemia-free survival rate and overall survival (OS were 17% and 19%, respectively. At five years, the cumulative probability of non-relapse mortality was 38%. In the univariable analyses of the influence of pre-transplant variables on OS, poor-risk cytogenetics, number of BM blasts (>26%, MDS overt AML and CB as stem cell source were

  19. 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. PMID:26910242

  20. DNA profiling in peripheral blood, buccal swabs, hair follicles and semen from a patient following allogeneic hematopoietic stem cells transplantation

    OpenAIRE

    Li, Ya-Ting; XIE, MING-KUN; Wu, Jin

    2014-01-01

    Allogeneic peripheral blood stem cells transplantation (allo-PBSCT) or allogeneic bone marrow transplantation (allo-BMT) have been widely used to treat patients exhibiting certain severe illnesses. However, previous studies have shown that the biological materials of allo-PBSCT or allo-BMT recipients may not constitute credible materials for personal identification. In the present study, four types of commonly used samples were collected from a male individual following gender-matched allo-BM...

  1. IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    蔡小矜

    2014-01-01

    Objective To explore the impact of interleukin-18(IL-18)single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation(allo-HSCT).Methods Single-nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis(PCR-SSP)in 93 recipients and their HLA matched sibling donors.Hematopoietic reconstitution,

  2. Allogeneic hematopoietic stem cells transplantation with reduced intensity conditioning regimen in children and adolescents with unfavorable forms of acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    E. V. Semenova

    2014-07-01

    Full Text Available Treatment results of allogeneic hematopoietic stem cells transplantation (allo-HSCT with myeloablative (MAC and reduced intensity (RIC conditioning regimen in children and adolescents with unfavorable forms of acute lymphoblastic leukemia (ALL were shown. One hundred and two ALL patients aged 1 to 21 years (mean – 12 years who received allo-HSCT from 2000 to 2010 (31 patients with RIC and 71 patients with MAC are included in the study. Analysis of overall and event-free survival in both groups showed comparable efficacy. The use of RIC as alternative conditioning regimen in children and adolescents with high risk ALL and poor general condition, comorbidities and infectious complications are discussed.

  3. EFFECTS OF INTERLEUKIN-4 ON GRANULOCYTE-MACROPHAGE-COLONY FORMATION FROM MURINE BONE MARROW CELLS AND HEMATOPOIETIC RECONSTITUTION FOLLOWING MURINE ALLOGENEIC BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; KerryAtkinson

    1994-01-01

    We investigated the effects of mouse recombinant IL-4 on hematopoiesis in vitro and in vivo.IL-4 alone was found to be incapable of stimulating colony formation,but it inhibited both IL-3-and GM-CSF-induced colony for-mation by murine hematopoietic progenitor cells.In contrast,colony formation induced by G-CSF was enhanced in the presence of IL-4.We also studied the influence of IL-4 on hematopoietie reconstiution after allogeneic bone marrow transplantation in a murine model,and found that IL-4 and G-CSF was significantly suppressed by IL-4.The combination of IL-4 and GM-CSF caused a significant decrease in the absolute mumber of meutrophils.

  4. Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission.

    Science.gov (United States)

    Yoon, Jae-Ho; Lee, Seok; Kim, Hee-Je; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Eom, Ki-Seong; Kim, Yoo-Jin; Min, Chang-Ki; Cho, Seok-Goo; Min, Woo-Sung; Lee, Jong Wook

    2016-03-29

    Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice consecutively, but GCV was sometimes delayed in patients without significant graft-vs-host disease (GVHD) by reducing immunosuppressive agents. In the entire group, CMV-reactivation showed poor overall survival (OS). To evaluate subsequent effects of CMV-reactivation, we excluded early relapse and deaths within 100 days, during which most of the CMV-reactivation occurred. Untreated CMV-reactivated group (n = 173) showed superior OS (83.8% vs. 61.7% vs. 74.0%, p acute leukemia. PMID:26883100

  5. Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two case reports and review of the literature.

    Science.gov (United States)

    Miyagi, T; Itonaga, H; Aosai, F; Taguchi, J; Norose, K; Mochizuki, K; Fujii, H; Furumoto, A; Ohama, M; Karimata, K; Yamanoha, A; Taniguchi, H; Sato, S; Taira, N; Moriuchi, Y; Fukushima, T; Masuzaki, H; Miyazaki, Y

    2015-08-01

    Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)-based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2 weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12 months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis. PMID:25970830

  6. ACTIVATION OF T. GONDII INFECTION AFTER ALLOGENEIC TRANSPLANTATION OF HEMATOPOIETIC STEM CELLS: DEPENDENCE ON TIME OF TRANSPLANTATION AND SEROLOGICAL STATUS OF THE PATIENTS

    Directory of Open Access Journals (Sweden)

    A. B. Chukhlovin

    2014-01-01

    Full Text Available The article focuses on aspects of T. gondii reactivation/reinfection in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT. We have observed 297 patients who received conditioning therapy and allogeneic grafts due to different oncohematological or lymphoproliferative diseases (1 to 60 years old, at a mediane of 19 years. Conditioning regimens were either myeloablative (35%, or non-myeloablative (65%. DNA diagnostics of T. gondii was performed on a regular basis at 0 to 6 months post-HSCT. IgG and IgM antibodies against T. gondii were determined in 78 patients before HSCT, as well as in their donors. T. gondii DNA post-transplant proved to be positive in 13% of blood specimens, 9% of cerebrospinal liquor samples, 11% of bronchoalveolar cell lavages, and in 5% of urine sediments. In adolescent patients (10 to 14 years old, an increased prevalence of T. gondii was found in patients who received myeloablative treatment (p = 0.01. When assessing posttransplant dynamics of T. gondii, we have revealed distinct increase in the pathogen excretion within 1st month after HSCT (p = 0.03. Finally, initial presence of IgG antibodies against T. gondii in the patients was associated with lower incidence of the pathogen reactivation post-transplant.

  7. Prognostic Factors on the Graft-versus-Host Disease-Free and Relapse-Free Survival after Adult Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Yao-Chung Liu

    2016-01-01

    Full Text Available The cure of hematologic disorders by allogeneic hematopoietic stem cell transplantation (HSCT is often associated with major complications resulting in poor outcome, including graft-versus-host disease (GVHD, relapse, and death. A novel composite endpoint of GVHD-free/relapse-free survival (GRFS in which events include grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death is censored to completely characterize the survival without mortality or ongoing morbidity. In this regard, studies attempting to identify the prognostic factors of GRFS are quite scarce. Thus, we reviewed 377 adult patients undergoing allogeneic HSCT between 2003 and 2013. The 1- and 2-year GRFS were 40.8% and 36.5%, respectively, significantly worse than overall survival and disease-free survival (log-rank p 2 (p 2 (p<0.001, being male (p=0.028, and hematologic malignancy (p=0.010 were significant for poor outcome. The events between 1-year GRFS and 2-year GRFS predominantly increased in relapsed patients. With prognostic factors of GRFS, we could evaluate the probability of real recovery following HSCT without ongoing morbidity.

  8. High rate of hematological responses to sorafenib in FLT3-ITD acute myeloid leukemia relapsed after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    De Freitas, Tiago; Marktel, Sarah; Piemontese, Simona; Carrabba, Matteo G; Tresoldi, Cristina; Messina, Carlo; Lupo Stanghellini, Maria Teresa; Assanelli, Andrea; Corti, Consuelo; Bernardi, Massimo; Peccatori, Jacopo; Vago, Luca; Ciceri, Fabio

    2016-06-01

    Relapse represents the most significant cause of failure of allogeneic hematopoietic stem cell transplantation (HSCT) for FLT3-ITD-positive acute myeloid leukemia (AML), and available therapies are largely unsatisfactory. In this study, we retrospectively collected data on the off-label use of the tyrosine kinase inhibitor sorafenib, either alone or in association with hypomethylating agents and adoptive immunotherapy, in 13 patients with post-transplantation FLT3-ITD-positive AML relapses. Hematological response was documented in 12 of 13 patients (92%), and five of 13 (38%) achieved complete bone marrow remission. Treatment was overall manageable in the outpatient setting, although all patients experienced significant adverse events, especially severe cytopenias (requiring a donor stem cell boost in five patients) and typical hand-foot syndrome. None of the patients developed graft-vs.-host disease following sorafenib alone, whereas this was frequently observed when this was given in association with donor T-cell infusions. Six patients are alive and in remission at the last follow-up, and four could be bridged to a second allogeneic HSCT, configuring a 65 ± 14% overall survival at 100 d from relapse. Taken together, our data suggest that sorafenib might represent a valid treatment option for patients with FLT3-ITD-positive post-transplantation relapses, manageable also in combination with other therapeutic strategies. PMID:26260140

  9. Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study.

    Science.gov (United States)

    Kanda, Junya; Hishizawa, Masakatsu; Utsunomiya, Atae; Taniguchi, Shuichi; Eto, Tetsuya; Moriuchi, Yukiyoshi; Tanosaki, Ryuji; Kawano, Fumio; Miyazaki, Yasushi; Masuda, Masato; Nagafuji, Koji; Hara, Masamichi; Takanashi, Minoko; Kai, Shunro; Atsuta, Yoshiko; Suzuki, Ritsuro; Kawase, Takakazu; Matsuo, Keitaro; Nagamura-Inoue, Tokiko; Kato, Shunichi; Sakamaki, Hisashi; Morishima, Yasuo; Okamura, Jun; Ichinohe, Tatsuo; Uchiyama, Takashi

    2012-03-01

    Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL. PMID:22234682

  10. Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Lee, Tae Hyang; Lee, Ji Yoon; Park, Sohye; Shin, Seung Hwan; Yahng, Seung-Ah; Yoon, Jae-Ho; Lee, Sung-Eun; Cho, Byung-Sik; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won

    2013-01-01

    Background Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-γ), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. Methods Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. Results Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. Conclusion This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD. PMID:23589790

  11. Influence of cyclosporine on the occurrence of nephrotoxicity after allogeneic hematopoietic stem cell transplantation: a systematic review

    OpenAIRE

    Juliana Bastoni da Silva; Maria Helena Melo Lima; Sílvia Regina Secoli

    2014-01-01

    Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A system...

  12. Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.

    Science.gov (United States)

    Costa-Lima, Carolina; Miranda, Eliana Cristina Martins; Colella, Marcos Paulo; Aranha, Francisco Jose Penteado; de Souza, Carmino Antonio; Vigorito, Afonso Celso; De Paula, Erich Vinicius

    2016-07-01

    The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which can be further refined by the incorporation of pre-hematopoietic cell transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin and albumin. β2-Microglobulin (β2-m) is a key component of the MHC class I complex, which is independently associated with mortality and frailty in the general population. We took advantage of our institutional protocol that includes measurement of pre-HCT β2-m serum levels in the most patients to investigate whether pre-transplant β2-m levels were associated with the risk of aGVHD. One hundred three consecutive patients submitted to allogeneic HCT, of which 26 developed grades II to IV aGVHD, were included in the analysis. β2-m was significantly associated with age and HCT-CI. Higher levels of β2-m were observed in patients who developed aGVHD (P = .008). In the multivariate Cox regression model, β2-m and HCT-CI remained independently associated with the risk of developing aGVHD. In conclusion, the association between β2-m and the occurrence of aGVHD suggests that the measurement of this protein before HCT might represent an additional element for risk stratification of aGVHD. PMID:27044906

  13. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Bjorn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The ...

  14. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report

    OpenAIRE

    C. Annaloro; Costa, A.; N.S. Fracchiolla; G. Mometto; S. Artuso; G. Saporiti; Tagliaferri, E.; GRIFONI, F.; Onida, F.; Cortelezzi, A.

    2015-01-01

    Key Clinical Message We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity.

  15. Severe fludarabine neurotoxicity after reduced intensity conditioning regimen to allogeneic hematopoietic stem cell transplantation: a case report.

    Science.gov (United States)

    Annaloro, Claudio; Costa, Antonella; Fracchiolla, Nicola S; Mometto, Gabriella; Artuso, Silvia; Saporiti, Giorgia; Tagliaferri, Elena; Grifoni, Federica; Onida, Francesco; Cortelezzi, Agostino

    2015-07-01

    We present a case of severe, irreversible neurotoxicity in a 55-year-old-patient with myelofibrosis undergoing hematopoietic stem cell transplantation following a reduced intensity conditioning including fludarabine. The patient developed progressive sensory-motor, visual and consciousness disturbances, eventually leading to death. MRI imaging pattern was unique and attributable to fludarabine neurotoxicity. PMID:26273463

  16. Graft-versus-leukemia effects of Wilms' tumor 1 protein-specific cytotoxic T lymphocytes in patients with chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-dong; LI Dan; HUANG Xiao-jun

    2010-01-01

    Background The role of Wilms' tumor 1 protein (WT1)-specific cytotoxic T cells (CTL) in eradicating chronic myeloid leukemia (CML) cells is to be established. The aim of this study was to determine whether WT1 contributed to the graft-versus-leukemia effects (GVLE) for CML following allogeneic hematopoietic stem cell transplantation (HSCT). Methods High-resolution human leukocyte antigen (HLA) class I genotyping was performed by sequence-specific polymerase chain reaction (PCR). Fifteen HLA-A~*2402 patients with CML who underwent allogeneic HSCT were enrolled in this study. We monitored the frequency of WT1-specific CTL by pentamer assay and the molecular minimal residual disease by real-time quantitative PCR.Results A CD8~+ T-cell response to WT1 was observed in 14 of 15 patients after HSCT. The median frequencies of WT1-CTL were 0.54%, 0.62%, 0.81% and 1.28% (%CD8) on days 30, 60, 90 and 180, respectively. The median frequency of WT1-CTL (1.38%) in patients with molecular remission (MoR) was significantly higher than that in those without MoR (0.38%) on day 30, while no significant differences between them were detected on days 60, 90 and 180. The increase of WT1-CTL was associated with a decrease in bcr-abl expression and MoR; and the decrease of WT1-CTL was associated with an increase in bcr-abl expression, suggesting a WT1 -driven GVL effect. WT1-CTL had a predominant effector-memory phenotype (CD45RO~+CD27~-CD57~+).Conclusions The emergence of WT1-CTL with an effector-memory phenotype is associated with GVLE in CML patients after HSCT. This will pave the way for the WT1 vaccines to enhance GVLE after HSCT in CML.

  17. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial.

    Science.gov (United States)

    Middeke, J M; Herbst, R; Parmentier, S; Bug, G; Hänel, M; Stuhler, G; Schäfer-Eckart, K; Rösler, W; Klein, S; Bethge, W; Bitz, U; Büttner, B; Knoth, H; Alakel, N; Schaich, M; Morgner, A; Kramer, M; Sockel, K; von Bonin, M; Stölzel, F; Platzbecker, U; Röllig, C; Thiede, C; Ehninger, G; Bornhäuser, M; Schetelig, J

    2016-02-01

    In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term disease control can only be achieved by allogeneic hematopoietic stem cell transplantation (HSCT). We studied the safety and efficacy of clofarabine-based salvage therapy. The study was designed as phase II, multicenter, intent-to-transplant (ITT) study. A total of 84 patients with r/r AML were enrolled. All patients received at least one cycle of CLARA (clofarabine 30 mg/m(2) and cytarabine 1 g/m(2), days 1-5). Chemo-responsive patients with a donor received HSCT in aplasia after first CLARA. Generally, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine (4 × 30 mg/m(2)) and melphalan (140 mg/m(2)). The median patient age was 61 years (range 40-75). On day 15 after start of CLARA, 26% of patients were in a morphologically leukemia-free state and 79% exposed a reduction in bone marrow blasts. Overall, 67% of the patients received HSCT within the trial. The primary end point, defined as complete remission after HSCT, was achieved by 60% of the patients. According to the ITT, overall survival at 2 years was 43% (95% confidence interval (CI), 32-54%). The 2-year disease-free survival for transplanted patients was 52% (95% CI, 40-69%). Clofarabine-based salvage therapy combined with allogeneic HSCT in aplasia shows promising results in patients with r/r AML. PMID:26283567

  18. Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study.

    Science.gov (United States)

    Vajdic, Claire M; Mayson, Eleni; Dodds, Anthony J; O'Brien, Tracey; Wilcox, Leonie; Nivison-Smith, Ian; Le Marsney, Renate; Daniels, Benjamin; Ashton, Lesley J

    2016-05-01

    We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups. PMID:26860637

  19. Busulfan, cyclophosphamide and fractionated total body irradiation as a conditioning regimen for allogeneic bone marrow transplantation in patients with non-lymphocytic hematopoietic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroshi [Jikei Univ., Tokyo (Japan). School of Medicine

    1996-11-01

    Allogeneic bone marrow transplantation (BMT) with the conditioning regimen of 8 mg/kg of busulfan (BUS), 120 mg/kg of cyclophosphamide (CPM) and 10 Gy of total body irradiation (TBI) was evaluated in the patients with non-lymphocytic hematopoietic malignancies. The disease distribution of the 22 patients was as follows; 14 in the standard risk group (SRG), 8 in the high risk group (HRG). SRG included the patients with acute myeloid leukemia (AML) in the first complete remission, chronic myelogenous leukemia (CML) in chronic phase and myelodysplastic syndrome with refractory anemia, while HRG included the patients with refractory AML and CML in blastic phase. The median age of patients was 33 years old (y.o.), and the median observation period was 34.5 months No relapse occurred, but 8 patients (36%) died of various complications. Ail the patients who died of interstitial pneumonitis (4 cases) were 40 y.o. and more. Acute graft-versus-host disease (GvHD) and chronic GvHD were clinically controllable. The probability of disease-free survival rate at 5 years (5y-DFS) was 50.0% in overall patients. The 5y-DFS was 57.1% in HRG (7 cases), while 54.3% in SRG (13 cases) donated from the HLA identical siblings (20 cases). In these 13 patients in SRG, the 5y-DFS was 100% in patients under 40 y.o. (6 cases), while the probability of disease-free survival rate at 3 years was 68.6% and the 5y-DFS was 0% in patients over 40 y.o. (7 cases). Our data indicate that the conditioning regimen combining BUS, CPM and TBI for allogeneic BMT is promising for the treatment of the patients of HRG and the patients under 40 y.o. in SRG. (author)

  20. Immunogenicity of decidual stromal cells in an epidermolysis bullosa patient and in allogeneic hematopoietic stem cell transplantation patients.

    Science.gov (United States)

    Kaipe, Helen; Carlson, Lena-Maria; Erkers, Tom; Nava, Silvia; Molldén, Pia; Gustafsson, Britt; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi; Sadeghi, Behnam; Alheim, Mats; Ringdén, Olle

    2015-06-15

    Allogeneic mesenchymal stromal cells (MSCs) are widely used in regenerative medicine, but little is known about their immunogenicity. In this study, we monitored the therapeutic and immunogenic effects of decidual stromal cells (DSCs) from term placentas when used as a therapy for generalized severe junctional epidermolysis bullosa (JEB) (previously termed Herlitz JEB), a lethal condition caused by the lack of functional laminin-332. An 11-month-old JEB patient was treated with five infusions of allogeneic DSCs within a 3-month period. Amniotic membranes (AMs) were applied to severe wounds. After the treatment, wounds started to heal in the middle of the blisters, but the improvements were transient. After two infusions of DSCs, the JEB patient had developed multispecific anti-HLA class-I antibodies. No antibodies to laminin-332 were detected, but the patient had high levels of anti-bovine serum albumin antibodies, which could bind to DSCs. Peripheral blood mononuclear cells (PBMCs) from the patient had a higher proliferative response to DSCs than to third-party PBMCs, which contrasts with the pattern observed in healthy donors. Human DSCs and MSCs induced similar xenoreactivity in mice. Two of 16 allogeneic stem cell-transplanted patients, treated with DSCs for graft-versus-host disease or hemorrhagic cystitis, showed a positive flow cytometric crossmatch test. One patient had anti-HLA antibodies before DSC infusion, whereas the other had no anti-HLA antibodies at any time. AM and DSC infusions may have improved the healing process in the JEB patient, but DSCs appeared to induce anti-HLA antibodies. The risk of alloimmunization by DSCs seems to be low in immunocompromised patients. PMID:25658253

  1. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia

    Directory of Open Access Journals (Sweden)

    Nishihori Taiga

    2010-10-01

    Full Text Available Abstract Optimal conditioning therapy for hematopoietic cell transplantation (HCT in acute myelogenous leukemia (AML remains undefined. We retrospectively compared outcomes of a consecutive series of 51 AML patients treated with oral busulfan (1 mg/kg every 6 hours for 4 days and cyclophosphamide (60 mg/kg IV × 2 days - (Bu/Cy with 100 consecutive AML patients treated with pharmacokinetic targeted IV busulfan (AUC

  2. Influence of cyclosporine on the occurrence of nephrotoxicity after allogeneic hematopoietic stem cell transplantation: a systematic review

    Directory of Open Access Journals (Sweden)

    Juliana Bastoni da Silva

    2014-10-01

    Full Text Available Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: "bone marrow transplantation" OR "stem cell transplantation" OR "grafting, bone marrow" AND cyclosporine OR cyclosporin OR "risk factors" AND "acute kidney injury" OR "acute kidney injuries" OR "acute renal failure" OR "acute renal failures" OR "nephrotoxicity". The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5% had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.

  3. Fecal calprotectin as a biomarker of intestinal graft versus host disease after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Lorenz, Fryderyk; Marklund, Stefan; Werner, Mårten; Palmqvist, Richard; Wahlin, Björn Engelbrekt; Wahlin, Anders

    2015-01-01

    The diagnosis of gastrointestinal graft versus host disease (GI-GVHD) is based on clinical symptoms and histological findings. In clinical practice, it is often difficult to decide whether abdominal symptoms in an allogeneic transplant recipient are caused by GVHD or other disorders. Endoscopic biopsies are helpful in establishing the diagnosis, but endoscopy is not always possible to perform due to poor general condition of the patients. No biomarkers are routinely used to predict GVHD. The aim of fecal calprotectin and alpha-1 antitrypsin testing in our study was to find out whether determination of the concentrations of these proteins may be used as a screening method for enteric GVHD. We studied prospectively 51 patients, 8 of whom developed GI-GVHD. Our data demonstrate that elevated fecal calprotectin levels were significantly associated with presence of GI-GVHD. We found a positive association between high F-calprotectin and severe gastrointestinal GVHD. In bivariate analysis, only calprotectin but not alpha-1 antitrypsin was independently associated with GI-GVHD. Testing for fecal calprotectin after allogeneic stem cell transplantation may be a useful screening tool. PMID:25605402

  4. Management of Myelodysplastic Syndrome Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation: A Study by the French Society of Bone Marrow Transplantation and Cell Therapies.

    Science.gov (United States)

    Guièze, Romain; Damaj, Gandhi; Pereira, Bruno; Robin, Marie; Chevallier, Patrice; Michallet, Mauricette; Vigouroux, Stéphane; Beguin, Yves; Blaise, Didier; El Cheikh, Jean; Roos-Weil, Damien; Thiebaut, Anne; Rohrlich, Pierre-Simon; Huynh, Anne; Cornillon, Jérôme; Contentin, Nathalie; Suarez, Felipe; Lioure, Bruno; Mohty, Mohamad; Maillard, Natacha; Clement, Laurence; François, Sylvie; Guillerm, Gaëlle; Yakoub-Agha, Ibrahim

    2016-02-01

    To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P = .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P = .007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT. PMID:26256942

  5. Implications and Management of Central Nervous System Involvement before Allogeneic Hematopoietic Cell Transplantation in Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Aldoss, Ibrahim; Al Malki, Monzr M; Stiller, Tracey; Cao, Thai; Sanchez, James F; Palmer, Joycelynne; Forman, Stephen J; Pullarkat, Vinod

    2016-03-01

    Acute lymphoblastic leukemia (ALL) with a history of central nervous system (CNS) involvement, either at diagnosis or relapse, poses challenges when the decision is made to proceed with allogeneic hematopoietic cell transplantation (alloHCT), as there is no evidence-based consensus on the best peri-transplantation approach to reduce subsequent CNS relapse risk. Here, we retrospectively analyzed outcomes of 87 patients with ALL and a history of CNS involvement who later underwent alloHCT. Patients with pretransplantation CNS involvement had higher risk of CNS relapse after transplantation (2-year CNS relapse: 9.6% versus 1.4%, P transplantation CNS relapse, EFS, or OS among patients presenting with CNS involvement at diagnosis, those with isolated CNS relapse, and those with combined bone marrow and CNS relapse before HCT. Interestingly, neither pretransplantation cranial irradiation, use of total body irradiation-based conditioning, nor post-transplantation prophylactic intrathecal chemotherapy were associated with a reduction of CNS relapse risk after transplantation. Thus, among the patients in the cohort studied, there was no clear benefit of CNS-directed therapy in the peri-transplantation period among patients who had prior CNS involvement and underwent subsequent alloHCT. PMID:26493564

  6. On Modeling Human Leukocyte Antigen-Identical Sibling Match Probability for Allogeneic Hematopoietic Cell Transplantation: Estimating the Need for an Unrelated Donor Source.

    Science.gov (United States)

    Besse, Kelsey; Maiers, Martin; Confer, Dennis; Albrecht, Mark

    2016-03-01

    Prior studies of allogeneic hematopoietic cell transplantation (HCT) therapy for the treatment of malignant or nonmalignant blood disorders assume a 30% likelihood that a patient will find a match among siblings and, therefore, a 70% likelihood of needing an unrelated donor source. This study utilizes birth data and statistical modeling to assess the adequacy of these estimates to describe the probability among US population cohorts segmented by race/ethnicity and age, including ages of greatest HCT utilization. Considerable variation in the likelihood of an HLA-identical sibling was found, ranging from 13% to 51%, depending upon patient age and race/ethnicity. Low sibling match probability, compounded with increased genetic diversity and lower availability among unrelated donors, put the youngest minority patients at the greatest risk for not finding a suitable related or unrelated HCT donor. Furthermore, the present 40-year decline in birth rates is expected to lead to 1.5-fold decrease in access to a matched sibling for today's young adults (18 to 44 years of age) when they reach peak HCT utilization years (near age 61 years) versus their contemporary adult counterparts (44 to 64 years). Understanding the sibling match probability by race/ethnicity and age cohort leads to forecasting the demand for unrelated HCT sources. PMID:26403513

  7. Subacute hepatic necrosis mimicking veno-occlusive disease in a patient with HFE H63D homozygosity after allogeneic hematopoietic cell transplantation with busulfan conditioning.

    Science.gov (United States)

    Chen, Sylvia; Osborn, James Dane; Chen, Xinjian; Boyer, Michael W; McDonald, George B; Hildebrandt, Gerhard Carl

    2015-12-01

    Busulfan is a commonly used chemotherapeutic agent in myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). It has been associated with sinusoidal-obstructive syndrome(SOS) as a life-threatening complication of myeloablative allo-HCT, yet it has not been found to cause severe hepatocellular injury, even in cases of significant accidental overdose.We report the case of a 31-year-old male with a history of high-risk myelodysplastic syndrome transitioning to acute myeloid leukemia, who in complete remission underwent allo-HCT using myeloablative busulfan–fludarabine conditioning, and who developed hepatic failure. While he met clinical criteria for SOS and was treated with defibrotide,liver biopsy demonstrated severe subacute hepatic necrosis and lacked characteristics of SOS. Further evaluation revealed that the patient was homozygous for the HFE H63D gene mutation, associated with hereditary hemochromatosis.Both Busulfan and iron overload related to HFE H63D homozygosity can cause oxidative stress resulting in cellular injury, and the cumulative effects of these risk factors are possibly responsible for the severe hepatocellular injury in this case, making our patient the first-known case of subacute hepatic necrosis related to busulfan administration. PMID:26497867

  8. Spontaneous thoracic air-leakage syndrome in patients following allogeneic hematopoietic stem cell transplantation: Causes, CT-follow up and patient outcome

    International Nuclear Information System (INIS)

    Objective: The purpose of this article is to describe and illustrate the acute and follow-up imaging features, clinical constellation and outcome of patients with thoracic air-leakage syndrome following allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods: Patients with evidence of thoracic air-leakage, i.e. spontaneous pneumomediastinum, spontaneous pneumothorax or interstitial emphysema after allo-HCT were retrospectively identified by a chart review. Acute and follow-up morphology, duration and patient outcome were analyzed on CT (HRCT or MSCT with HR-reconstructions). Correlation was made with histological results of transbronchial biopsy. Results: The 6 patients included (3 male and 3 female, 14-64 years old) with thoracic air-leakage after allo-HCT all had histologically proven bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP). Thoracic air-leakage consisted of spontaneous pneumomediastinum associated with active invasive pulmonary aspergillosis (IPA) in 4/6 and spontaneous pneumothorax or interstitial emphysema each in 1/6 patients. Duration of thoracic air-leakage was 7-135 days. Of the patients with spontaneous pneumomediastinum, 3/4 died of IPA. One patient survived until complete regression of spontaneous pneumomediastinum. One patient died 7 days after spontaneous pneumothorax and one survived developing chronic interstitial emphysema. Conclusion: In all cases, thoracic air-leakage was associated to BO or BOOP. In the majority of cases with additional IPA, thoracic air-leakage is more indicative for severity of pulmonary disease than a life-threatening entity itself

  9. Spontaneous thoracic air-leakage syndrome in patients following allogeneic hematopoietic stem cell transplantation: Causes, CT-follow up and patient outcome

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, Monika [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)]. E-mail: monika.vogel@med.uni-tuebingen.de; Brodoefel, Harald [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Bethge, Wolfgang [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Faul, Christoph [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Hartmann, Joerg [Department of Internal Medicine-Oncology, Eberhard-Karls-University, Ottfried-Mueller-Str. 5, 72070 Tuebingen (Germany); Schimmel, Heiko [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Wehrmann, Manfred [Department of Pathology, Eberhard-Karls-University, Liebermeisterstrasse 8, 72076 Tuebingen (Germany); Claussen, Claus D. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Horger, Marius [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2006-12-15

    Objective: The purpose of this article is to describe and illustrate the acute and follow-up imaging features, clinical constellation and outcome of patients with thoracic air-leakage syndrome following allogeneic hematopoietic stem cell transplantation (allo-HCT). Methods: Patients with evidence of thoracic air-leakage, i.e. spontaneous pneumomediastinum, spontaneous pneumothorax or interstitial emphysema after allo-HCT were retrospectively identified by a chart review. Acute and follow-up morphology, duration and patient outcome were analyzed on CT (HRCT or MSCT with HR-reconstructions). Correlation was made with histological results of transbronchial biopsy. Results: The 6 patients included (3 male and 3 female, 14-64 years old) with thoracic air-leakage after allo-HCT all had histologically proven bronchiolitis obliterans (BO) or bronchiolitis obliterans organizing pneumonia (BOOP). Thoracic air-leakage consisted of spontaneous pneumomediastinum associated with active invasive pulmonary aspergillosis (IPA) in 4/6 and spontaneous pneumothorax or interstitial emphysema each in 1/6 patients. Duration of thoracic air-leakage was 7-135 days. Of the patients with spontaneous pneumomediastinum, 3/4 died of IPA. One patient survived until complete regression of spontaneous pneumomediastinum. One patient died 7 days after spontaneous pneumothorax and one survived developing chronic interstitial emphysema. Conclusion: In all cases, thoracic air-leakage was associated to BO or BOOP. In the majority of cases with additional IPA, thoracic air-leakage is more indicative for severity of pulmonary disease than a life-threatening entity itself.

  10. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital.

    Science.gov (United States)

    Wang, Meng; Wang, Wenjia; Abeywardane, Ayesha; Adikarama, Malinthi; McLornan, Donal; Raj, Kavita; de Lavallade, Hugues; Devereux, Stephen; Mufti, Ghulam J; Pagliuca, Antonio; Potter, Victoria T; Mijovic, Aleksandar

    2015-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of hematopoietic stem cell transplantation (HSCT); it is often refractory to treatment and carries a high mortality. To improve understanding of the incidence, risk factors, and clinical outcome of post-transplantation AIHA, we analyzed 533 patients who received allogeneic HSCT, and we identified 19 cases of AIHA after HSCT (overall incidence, 3.6%). The median time to onset, from HSCT to AIHA, was 202 days. AIHA was associated with HSCT from unrelated donors (hazard ratio [HR], 5.28; 95% confidence interval [CI], 1.22 to 22.9; P = .026). In the majority (14 of 19; 74%) of AIHA patients, multiple agents for treatment were required, with only 9 of 19 (47%) patients achieving complete resolution of AIHA. Patients with post-transplantation AIHA had a higher overall mortality (HR, 2.48; 95% CI, 1.33 to 4.63; P = .004), with 36% (4 of 11 cases) of deaths attributable to AIHA. PMID:25262883

  11. Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Schliemann, Christoph; Gutbrodt, Katrin L; Kerkhoff, Andrea; Pohlen, Michele; Wiebe, Stefanie; Silling, Gerda; Angenendt, Linus; Kessler, Torsten; Mesters, Rolf M; Giovannoni, Leonardo; Schäfers, Michael; Altvater, Bianca; Rossig, Claudia; Grünewald, Inga; Wardelmann, Eva; Köhler, Gabriele; Neri, Dario; Stelljes, Matthias; Berdel, Wolfgang E

    2015-05-01

    The antibody-based delivery of IL2 to extracellular targets expressed in the easily accessible tumor-associated vasculature has shown potent antileukemic activity in xenograft and immunocompetent murine models of acute myelogenous leukemia (AML), especially in combination with cytarabine. Here, we report our experience with 4 patients with relapsed AML after allogeneic hematopoietic stem cell transplantation (allo-HSCT), who were treated with the immunocytokine F16-IL2, in combination with low-dose cytarabine. One patient with disseminated extramedullary AML lesions achieved a complete metabolic response identified by PET/CT, which lasted 3 months. Two of 3 patients with bone marrow relapse achieved a blast reduction with transient molecular negativity. One of the 2 patients enjoyed a short complete remission before AML relapse occurred 2 months after the first infusion of F16-IL2. In line with a site-directed delivery of the cytokine, F16-IL2 led to an extensive infiltration of immune effector cells in the bone marrow. Grade 2 fevers were the only nonhematologic side effects in 2 patients. Grade 3 cytokine-release syndrome developed in the other 2 patients but was manageable in both cases with glucocorticoids. The concept of specifically targeting IL2 to the leukemia-associated stroma deserves further evaluation in clinical trials, especially in patients who relapse after allo-HSCT. PMID:25672398

  12. Low Counts of B Cells, Natural Killer Cells, Monocytes, Dendritic Cells, Basophils, and Eosinophils are Associated with Postengraftment Infections after Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Podgorny, Peter J; Pratt, Laura M; Liu, Yiping; Dharmani-Khan, Poonam; Luider, Joanne; Auer-Grzesiak, Iwona; Mansoor, Adnan; Williamson, Tyler S; Ugarte-Torres, Alejandra; Hoegh-Petersen, Mette; Khan, Faisal M; Larratt, Loree; Jimenez-Zepeda, Victor H; Stewart, Douglas A; Russell, James A; Daly, Andrew; Storek, Jan

    2016-01-01

    Hematopoietic cell transplant (HCT) recipients are immunocompromised and thus predisposed to infections. We set out to determine the deficiency of which immune cell subset(s) may predispose to postengraftment infections. We determined day 28, 56, 84, and 180 blood counts of multiple immune cell subsets in 219 allogeneic transplant recipients conditioned with busulfan, fludarabine, and Thymoglobulin. Deficiency of a subset was considered to be associated with infections if the low subset count was significantly associated with subsequent high infection rate per multivariate analysis in both discovery and validation cohorts. Low counts of monocytes (total and inflammatory) and basophils, and low IgA levels were associated with viral infections. Low plasmacytoid dendritic cell (PDC) counts were associated with bacterial infections. Low inflammatory monocyte counts were associated with fungal infections. Low counts of total and naive B cells, total and CD56(high) natural killer (NK) cells, total and inflammatory monocytes, myeloid dendritic cells (MDCs), PDCs, basophils and eosinophils, and low levels of IgA were associated with any infections (due to any pathogen or presumed). In conclusion, deficiencies of B cells, NK cells, monocytes, MDCs, PDCs, basophils, eosinophils, and/or IgA plasma cells appear to predispose to postengraftment infections. PMID:26363444

  13. Factors Predicting Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Hematopoietic Cell Transplantation: Multivariable Analysis from a Single Center.

    Science.gov (United States)

    Solh, Melhem; Zhang, Xu; Connor, Katelin; Brown, Stacey; Solomon, Scott R; Morris, Lawrence E; Holland, H Kent; Bashey, Asad

    2016-08-01

    The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, graft-versus-host disease (GVHD), and nonrelapse death. A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT. We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grades III to IV, chronic GVHD requiring immunosuppression, relapse, or death in 531 consecutive adult patients who received an allo-HCT between 2006 and 2014 at our center. Median follow-up of living patients was 46 months (range, 12 to 123). HLA matched related donor (MRD, n = 198, 37%), matched unrelated donor (MUD, n = 205, 39%), and haploidentical donor with post-transplant cyclophosphamide (HID, n = 128, 24%) were used. Thirty-six percent of patients had a high/very-high Dana Farber disease risk index (DRI). Estimated rates of GRFS at 1 and 2 years after MRD, MUD, and HID transplantations were 34% and 26%, 26% and 17%, and 33% and 31%, respectively, with MRD recipients having a better GRFS than MUD (P disease risk, stem cell source, and donor type. Importantly, MUDs produce inferior GRFS to MRDs, whereas HIDs do not. PMID:27095692

  14. Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Wang, Yu-Tong; Kong, Yuan; Song, Yang; Han, Wei; Zhang, Yuan-Yuan; Zhang, Xiao-Hui; Chang, Ying-Jun; Jiang, Zheng-Fan; Huang, Xiao-Jun

    2016-08-01

    Poor graft function (PGF) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The question of whether the bone marrow (BM) immune microenvironment is involved in the pathogenesis of PGF remains unresolved. In total, 10 patients with PGF, 30 matched patients with good graft function after allo-HSCT, and 15 healthy donors were enrolled in this nested case-control study. The Th1, Th2, Tc1, Tc2, and active phenotypes were analyzed by flow cytometry. IFN-γ and IL-4 levels in BM plasma were evaluated using cytometric beads assay. Relative to other subjects, patients with PGF had significantly higher proportions of stimulated CD4(+) and CD8(+) T cells that produced IFN-γ (Th1 and Tc1 cells) but notably decreased proportions of IL-4-producing T cells (Th2 and Tc2 cells), resulting in a shift of the IFN-γ/IL-4 ratio towards a type 1 response and an elevated percentage of activated CD8(+) T cells. Changes in IFN-γ and IL-4 levels in BM plasma were consistent with the cellular results. Our results suggest that dysregulated T cell responses may contribute to the occurrence of PGF after HSCT. PMID:27131864

  15. Umbilical cord blood-derived mesenchymal stem cells ameliorate graft-versus-host disease following allogeneic hematopoietic stem cell transplantation through multiple immunoregulations.

    Science.gov (United States)

    Wu, Qiu-Ling; Liu, Xiao-Yun; Nie, Di-Min; Zhu, Xia-Xia; Fang, Jun; You, Yong; Zhong, Zhao-Dong; Xia, Ling-Hui; Hong, Mei

    2015-08-01

    Although mesenchymal stem cells (MSCs) are increasingly used to treat graft-versus-host disease (GVHD), their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells, Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations. PMID:26223913

  16. The PD-1 Axis Enforces an Anatomical Segregation of CTL Activity that Creates Tumor Niches after Allogeneic Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Michonneau, David; Sagoo, Pervinder; Breart, Béatrice; Garcia, Zacarias; Celli, Susanna; Bousso, Philippe

    2016-01-19

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a curative treatment for hematologic malignancies, relies on donor cytotoxic T lymphocyte (CTL)-mediated graft-versus-leukemia (GVL) effect. Major complications of HSCT are graft-versus-host disease (GVHD) that targets specific tissues and tumor relapses. However, the mechanisms dictating the anatomical features of GVHD and GVL remain unclear. Here, we show that after HSCT, CTLs exhibited different killing activity in distinct tissues, being highest in the liver and lowest in lymph nodes. Differences were imposed by the microenvironment, partly through differential PD-1 ligand expression, which was strongly elevated in lymph nodes. Two-photon imaging revealed that PD-1 blockade restored CTL sensitivity to antigen and killing in lymph nodes. Weak CTL activity in lymph nodes promoted local tumor escape but could be reversed by anti-PD-1 treatment. Our results uncover a mechanism generating an anatomical segregation of CTL activity that might dictate sites of GVHD and create niches for tumor escape. PMID:26795248

  17. 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...... score 6 and 4% in score 7. There was no difference in overall survival (OS) at 5 years between HLA-identical siblings (55% (48-64)) and WMUD (59% (41-84)), P=0.82. In contrast, OS was significantly worse for MM (37% (29-48) P=0.005) due to a significant excess of transplant-related mortality. Also OS...... worsened significantly when EBMT risk score increased. HLA matching had no significant impact on relapse (siblings: 24% (21-27); WMUD: 35% (26-44), P=0.11 and MM: 21% (18-24), P=0.81); alemtuzumab T-cell depletion and stem cell source (peripheral blood) were associated with an increased risk. Our findings...

  18. Successful Allogeneic Hematopoietic Stem Cell Transplantation of a Patient Suffering from Type II Congenital Dyserythropoietic Anemia A Rare Case Report from Western India

    Science.gov (United States)

    Modi, Gaurang; Shah, Sandip; Panchal, Harsha; Patel, Apurva; Uparkar, Urmila; Anand, Asha; Parikh, Sonia; Patel, Kinnari; Shah, Kamlesh; Revannasiddaiah, Swaroop

    2015-01-01

    The most frequent form of congenital dyserythropoiesis (CDA) is congenital dyserythropoietic anemia II (CDA II). CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT) at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV), which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother). The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin). Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT. PMID:25692053

  19. Successful Allogeneic Hematopoietic Stem Cell Transplantation of a Patient Suffering from Type II Congenital Dyserythropoietic Anemia A Rare Case Report from Western India

    Directory of Open Access Journals (Sweden)

    Gaurang Modi

    2015-01-01

    Full Text Available The most frequent form of congenital dyserythropoiesis (CDA is congenital dyserythropoietic anemia II (CDA II. CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV, which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother. The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin. Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT.

  20. Lung function score including a parameter of small airway disease as a highly predictive indicator of survival after allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Nakamae, Mika; Yamashita, Mariko; Koh, Hideo; Nishimoto, Mitsutaka; Hayashi, Yoshiki; Nakane, Takahiko; Nakashima, Yasuhiro; Hirose, Asao; Hino, Masayuki; Nakamae, Hirohisa

    2016-06-01

    Some studies on the predictive value of determining pulmonary function prior to allogeneic hematopoietic cell transplantation (allo-HCT) have shown a significant association between pulmonary function test (PFT) parameters and pulmonary complications, and mortality. However, the percentage of patients showing abnormalities in pretransplant PFT parameters is low. We comprehensively evaluated the effect of pretransplant PFT parameters, including a marker of small airway disease (ratio of the airflow rate of 50% vital capacity to the airflow rate of 25% vital capacity (V˙50/V˙25), on outcomes in 206 evaluable patients who underwent allo-HCT at our institute. Notable among the significant parameters in a univariable analysis, V˙50/V˙25 was the most powerful indicator of survival following allo-HCT (delta-Akaike information criterion [∆AIC] = 12.47, ∆χ(2)  = 14.47; P = 0.0001). Additionally, a pretransplant lung function score (pLFS) established by applying three parameters with superior predictive values including V˙50/V˙25 represented a better discriminating variable for the prediction of survival. Our data demonstrate that a pLFS incorporating a parameter of small airway disease, rather than the parameters of central airway obstruction, may be useful for predicting patient survival following allo-HCT. PMID:27018997

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

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R; Høyer-Hansen, G; Heilmann, C; Ullum, H; Müller, K; Jacobsen, N

    2011-01-01

    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 of the...

  2. Association between decreasing trend in the mortality of adult T-cell leukemia/lymphoma and allogeneic hematopoietic stem cell transplants in Japan: analysis of Japanese vital statistics and Japan Society for Hematopoietic Cell Transplantation (JSHCT)

    International Nuclear Information System (INIS)

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with a very poor outcome. However, several studies have shown a progress in the treatment. To evaluate the effect of the progress in the treatment of ATLL in a whole patient population, we used vital statistics data and estimated age-adjusted mortality and trends in the mortality from 1995 to 2009. Since allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has been introduced as a modality with curative potential during study period, we also evaluated the association of the annual number of allo-HSCT and the trend of the mortality of ATLL. Endemic (Kyushu) and non-endemic areas (others) were evaluated separately. Significance in the trend of mortality was evaluated by joinpoint regression analysis. During the study period, a total of 14 932 patients died of ATLL in Japan, and mortality decreased significantly in both areas (annual percent change (95% confidence interval (CI)): Kyushu, −3.1% (−4.3, −1.9); others, −3.4% (−5.3, −1.5)). This decreasing trend in mortality seems to be associated with an increase in the number of allo-HSCTs (Kyushu, R-squared=0.70, P=0.003; and others, R-squared=0.55, P=0.058). This study reveals that the mortality of ATLL is now significantly decreasing in Japan and this decreasing trend might be associated with allo-HSCT

  3. Phase II Study of Haploidentical Natural Killer Cell Infusion for Treatment of Relapsed or Persistent Myeloid Malignancies Following Allogeneic Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Shaffer, Brian C; Le Luduec, Jean-Benoit; Forlenza, Christopher; Jakubowski, Ann A; Perales, Miguel-Angel; Young, James W; Hsu, Katharine C

    2016-04-01

    We conducted a phase 2 study to determine the efficacy of HLA-haploidentical related donor natural killer (NK) cells after cyclophosphamide-based lymphodepletion in patients with relapsed or progressive acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) following allogeneic hematopoietic cell transplantation (HCT). Eight patients (2 with MDS and 6 with AML) were treated with cyclophosphamide 50 mg/kg on day -3 and day -2 before infusion of NK cells isolated from a haploidentical related donor. One patient also received fludarabine 25 mg/m(2)/day for 4 days. Six doses of 1 million units of interleukin-2 (IL-2) were administered on alternating days beginning on day -1. The median number of NK cells infused was 10.6 × 10(6)/kg (range, 4.3 to 22.4 × 10(6)/kg), and the median number of CD3 cells infused was 2.1 × 10(3)/kg (range, 1.9 to 40 × 10(3)/kg). NK infusions were well tolerated, with a median time to neutrophil recovery of 19 days (range, 7 days to not achieved) and no incidence of graft-versus-host disease after NK infusion. One patient with AML and 1 patient with MDS achieved a complete response, but relapsed at 1.7 and 1.8 months, respectively. One patient with MDS experienced resolution of dysplastic features but persistence of clonal karyotype abnormalities; this patient was stable at 65 months after NK cell therapy. The median duration of survival was 12.9 months (range, 0.8 to 65.3 months). Chimerism analysis of CD3(-)/CD56(+) peripheral blood cells did not detect any circulating haploidentical NK cells after infusion. NK phenotyping was performed in 7 patients during and after IL-2 infusion. We found a slight trend toward greater expression of KIR2DL2/2DL3/2DS2 (5% versus 28%; P = .03) at 14 days in patients who survived longer than 6 months from NK cell infusion (n = 4) compared with those who died within 6 months of NK cell therapy (n = 3). In summary, our data support the safety of haploidentical NK cell

  4. Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma.

    Science.gov (United States)

    Chen, Robert; Palmer, Joycelynne M; Thomas, Sandra H; Tsai, Ni-Chun; Farol, Len; Nademanee, Auayporn; Forman, Stephen J; Gopal, Ajay K

    2012-06-28

    Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT. PMID:22611160

  5. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors.

    Science.gov (United States)

    Shanavas, Mohamed; Popat, Uday; Michaelis, Laura C; Fauble, Veena; McLornan, Donal; Klisovic, Rebecca; Mascarenhas, John; Tamari, Roni; Arcasoy, Murat O; Davies, James; Gergis, Usama; Ukaegbu, Oluchi C; Kamble, Rammurti T; Storring, John M; Majhail, Navneet S; Romee, Rizwan; Verstovsek, Srdan; Pagliuca, Antonio; Vasu, Sumithira; Ernst, Brenda; Atenafu, Eshetu G; Hanif, Ahmad; Champlin, Richard; Hari, Paremeswaran; Gupta, Vikas

    2016-03-01

    The impact of Janus kinase (JAK) 1/2 inhibitor therapy before allogeneic hematopoietic cell transplantation (HCT) has not been studied in a large cohort in myelofibrosis (MF). In this retrospective multicenter study, we analyzed outcomes of patients who underwent HCT for MF with prior exposure to JAK1/2 inhibitors. One hundred consecutive patients from participating centers were analyzed, and based on clinical status and response to JAK1/2 inhibitors at the time of HCT, patients were stratified into 5 groups: (1) clinical improvement (n = 23), (2) stable disease (n = 31), (3) new cytopenia/increasing blasts/intolerance (n = 15), (4) progressive disease: splenomegaly (n = 18), and (5) progressive disease: leukemic transformation (LT) (n = 13). Overall survival (OS) at 2 years was 61% (95% confidence interval [CI], 49% to 71%). OS was 91% (95% CI, 69% to 98%) for those who experienced clinical improvement and 32% (95% CI, 8% to 59%) for those who developed LT on JAK1/2 inhibitors. In multivariable analysis, response to JAK1/2 inhibitors (P = .03), dynamic international prognostic scoring system score (P = .003), and donor type (P = .006) were independent predictors of survival. Among the 66 patients who remained on JAK1/2 inhibitors until stopped for HCT, 2 patients developed serious adverse events necessitating delay of HCT and another 8 patients had symptoms with lesser severity. Adverse events were more common in patients who started tapering or abruptly stopped their regular dose ≥6 days before conditioning therapy. We conclude that prior exposure to JAK1/2 inhibitors did not adversely affect post-transplantation outcomes. Our data suggest that JAK1/2 inhibitors should be continued near to the start of conditioning therapy. The favorable outcomes of patients who experienced clinical improvement with JAK1/2 inhibitor therapy before HCT were particularly encouraging, and need further prospective validation. PMID:26493563

  6. Dangers resulting from DNA profiling of biological materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with regard to forensic genetic analysis.

    Science.gov (United States)

    Jacewicz, R; Lewandowski, K; Rupa-Matysek, J; Jędrzejczyk, M; Berent, J

    2015-01-01

    The study documents the risk that comes with DNA analysis of materials derived from patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in forensic genetics. DNA chimerism was studied in 30 patients after allo-HSCT, based on techniques applied in contemporary forensic genetics, i.e. real-time PCR and multiplex PCR-STR with the use of autosomal DNA as well as Y-DNA markers. The results revealed that the DNA profile of the recipient's blood was identical with the donor's in the majority of cases. Therefore, blood analysis can lead to false conclusions in personal identification as well as kinship analysis. An investigation of buccal swabs revealed a mixture of DNA in the majority of recipients. Consequently, personal identification on the basis of stain analysis of the same origin may be impossible. The safest (but not ideal) material turned out to be the hair root. Its analysis based on autosomal DNA revealed 100% of the recipient's profile. However, an analysis based on Y-chromosome markers performed in female allo-HSCT recipients with male donors demonstrated the presence of donor DNA in hair cells - similarly to the blood and buccal swabs. In the light of potential risks arising from DNA profiling of biological materials derived from persons after allotransplantation in judicial aspects, certain procedures were proposed to eliminate such dangers. The basic procedures include abandoning the approach based exclusively on blood collection, both for kinship analysis and personal identification; asking persons who are to be tested about their history of allo-HSCT before sample collection and profile entry in the DNA database, and verification of DNA profiling based on hair follicles in uncertain cases. PMID:27543957

  7. The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation Over Chemotherapy Alone in the Treatment of Acute Myeloid Leukemia Patients with Mixed Lineage Leukemia (MLL) Rearrangements

    Science.gov (United States)

    Yang, Hua; Huang, Sai; Zhu, Cheng-Ying; Gao, Li; Zhu, Hai-Yan; Lv, Na; Jing, Yu; Yu, Li

    2016-01-01

    Background Acute myeloid leukemia (AML) patients with mixed lineage leukemia (MLL) gene rearrangements always had a very poor prognosis. In this study, we report the incidence of MLL rearrangements in AML patients using gene analysis, as well as the clinical significance and prognostic features of these rearrangements. Material/Methods This retrospective study took place from April 2008 to November 2011 in the People’s Liberation Army General Hospital. A total 433 AML patients were screened by multiple nested reverse transcription polymerase chain reaction (RT-PCR) to determine the incidence of the 11 MLL gene rearrangements. There were 68 cases of MLL gene rearrangements, for a positive rate of 15.7%. A total of 24 patients underwent allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and 34 patients received at least 4 cycles of chemotherapy. Ten patients were lost to follow-up. Results The median follow-up was 29 months. The complete remission (CR) rate was 85.4%. The overall survival (OS) was 57.4±5.9 months for the Allo-HSCT group and 21.0±2.1 months for the chemotherapy group. The Allo-HSCT group had superior survival compared with the chemotherapy group (5-year OS: 59±17% vs. 13±8%, P0.05). Multivariate analysis showed that transplantation, platelets >50×109/L at onset, and CR are associated with a better OS in MLL rearranged AML patients. Patients with thrombocytopenia and extramedullary involvement were prone to relapse. Conclusions Our results suggest that Allo-HSCT is superior to chemotherapy alone for treating MLL rearranged AML patients. Patients treated with Allo-HSCT have a better prognosis and a longer survival. CR is an independent prognostic factor for OS, and extramedullary involvement is an independent prognostic factor for DFS. MLL rearranged AML patients with thrombocytopenia at onset <50×109 had very bad OS and DFS. PMID:27373985

  8. Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell transplantation: impact of cytochrome p450 polymorphisms and comedications on initial and subsequent trough levels.

    Science.gov (United States)

    Gautier-Veyret, Elodie; Fonrose, Xavier; Tonini, Julia; Thiebaut-Bertrand, Anne; Bartoli, Mireille; Quesada, Jean-Louis; Bulabois, Claude-Eric; Cahn, Jean-Yves; Stanke-Labesque, Françoise

    2015-04-01

    Voriconazole (VRC) plasma trough concentrations (Cmin) are highly variable, and this could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We aimed to describe the intra- and interindividual variation of VRC Cmin throughout the course of VRC therapy and to identify the determinants of this variation. Clinical data, medications, and VRC Cmin (n = 308) of 33 AHSCT patients were retrospectively collected. Cytochrome P450 (CYP450) genotypes of CYP2C19, CYP3A4, and CYP3A5 patients were retrospectively determined before allografting, and a combined genetic score was calculated for each patient. The higher the genetic score, the faster the metabolism of the patient. The VRC Cmin inter- and intraindividual coefficients of variation were 84% and 68%, respectively. The VRC dose (D) was correlated to VRC Cmin (r = 0.412, P oral administration. The administration route and the genetic score significantly affected the initial VRC Cmin. Considering oral therapy, patients with a genetic score of 2 (P = 0.009). Subsequent VRC Cmin remained influenced by the genetic score (P = 0.004) but were also affected by pump proton inhibitor comedication (P < 0.0001). The high variability of VRC Cmin in AHSCT patients is partially explained by the route of administration, treatment with pump proton inhibitors, and the combined genetic score. This study suggests the interest in combined genetic score determination to individualize a priori the VRC dose and underlines the need for longitudinal therapeutic drug monitoring to adapt subsequent doses to maintain the VRC Cmin within the therapeutic range. PMID:25645831

  9. Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.

    Science.gov (United States)

    Shono, Yusuke; Docampo, Melissa D; Peled, Jonathan U; Perobelli, Suelen M; Velardi, Enrico; Tsai, Jennifer J; Slingerland, Ann E; Smith, Odette M; Young, Lauren F; Gupta, Jyotsna; Lieberman, Sophia R; Jay, Hillary V; Ahr, Katya F; Porosnicu Rodriguez, Kori A; Xu, Ke; Calarfiore, Marco; Poeck, Hendrik; Caballero, Silvia; Devlin, Sean M; Rapaport, Franck; Dudakov, Jarrod A; Hanash, Alan M; Gyurkocza, Boglarka; Murphy, George F; Gomes, Camilla; Liu, Chen; Moss, Eli L; Falconer, Shannon B; Bhatt, Ami S; Taur, Ying; Pamer, Eric G; van den Brink, Marcel R M; Jenq, Robert R

    2016-05-18

    Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon. PMID:27194729

  10. Murine cytomegalovirus immediate-early 1 gene expression correlates with increased GVHD after allogeneic hematopoietic cell transplantation in recipients reactivating from latent infection.

    Directory of Open Access Journals (Sweden)

    Senthilnathan Palaniyandi

    Full Text Available The success of allogeneic (allo hematopoietic cell transplantation (HCT is limited by its treatment related complications, mostly graft versus host disease (GVHD and fungal and viral infections. CMV reactivation after HCT has been associated with increased morbidity and mortality, and a causal relation between GVHD, immunosuppressive therapy and vice versa has been postulated. Using a low GVHD severity murine HCT model, we assessed the role of MCMV reactivation and GVHD development. BALB/c mice were infected with either murine CMV (MCMV or mock and monitored for 25 weeks to establish latency, followed by sublethal irradiation conditioning and infusion of bone marrow plus splenocytes from either syngeneic (syn BALB/c or allo B10.D2 donors. Engraftment of allo donor cells was confirmed by PCR for D2Mit265 gene product size. Day+100 mortality and overall GVHD severity in allo MCMV pre-infected recipients was higher than in allo mock controls. Pathologic changes of lung and liver GVHD in immediate-early gene 1 (IE1 positive recipients were significantly increased compared to mock controls, and were only slightly increased in IE1 negative. No significant gut injury was seen in any group. Aggravated lung injury in IE1 positive recipients correlated with higher BAL cell counts both for total cells and for CD4+ T cells when compared with mock controls, and also with protein expression of lung IFN-gamma and liver TNF. No evidence for CMV specific morphologic changes was seen on histopathology in any organ of IE1 positive recipients, suggesting that CMV reactivation is related to increased GVHD severity but does not require active CMV disease, strengthening the concept of a reciprocal relationship between CMV and GVHD.

  11. SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

    Science.gov (United States)

    Shin, Seung-Hwan; Lee, Ji Yoon; Lee, Tae Hyang; Park, So-Hye; Yahng, Seung-Ah; Yoon, Jae-Ho; Lee, Sung-Eun; Cho, Byung-Sik; Lee, Dong-Gun; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won

    2015-01-01

    Background The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. Methods Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). Results Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. Conclusion We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia. PMID:25830129

  12. Extracorporeal Photopheresis for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    Shaughnessy, Paul J; Bolwell, Brian J; van Besien, Koen; Mistrik, Martin; Grigg, Andrew; Dodds, Anthony; Prince, H Miles; Durrant, Simon; Ilhan, Osman; Parenti, Dennis; Rogers, Jon; Gallo, Jose; Foss, Francine; Apperley, Jane; Zhang, Mei-Jie; Horowitz, Mary M; Abhyankar, Sunil

    2012-01-01

    Summary Graft-versus-host disease (GVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photopheresis (ECP) can modulate APC function and benefit some patients with GVHD. We report the results of a study using ECP administered prior to a standard myeloablative preparative regimen intended to prevent GVHD. Grade II-IV aGVHD developed in 9 (30%) of 30 recipients of HLA-matched related transplants and 13 (42%) of 31 recipients of HLA-matched unrelated or HLA-mismatched related donor transplants. Actuarial estimates of overall survival (OS) at day 100 and 1 year post transplant were 89% (95% CI, 78%-94%) and 77% (95% CI, 64%-86%), respectively. There were no unexpected adverse effects of ECP. Historical controls receiving similar conditioning and GVHD prophylaxis regimens but no ECP were identified from the database of the Center for International Blood and Marrow Transplant Research and multivariate analysis indicated a lower risk of grade II-IV aGVHD in patients receiving ECP (p=0.04). Adjusted OS at one year was 83% in the ECP study group and 67% in the historical control group (relative risk 0.44, 95% CI, 0.24-0.80) (p= 0.007). These preliminary data may indicate a potential survival advantage with ECP for transplant recipients undergoing standard myeloablative hematopoietic cell transplantation. PMID:19915634

  13. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults with Chronic Myeloid Leukemia: A CIBMTR Cohort Analysis.

    Science.gov (United States)

    Chaudhury, Sonali; Sparapani, Rodney; Hu, Zhen-Huan; Nishihori, Taiga; Abdel-Azim, Hisham; Malone, Adriana; Olsson, Richard; Hamadani, Mehdi; Daly, Andrew; Bacher, Ulrike; Wirk, Baldeep M; Kamble, Rammurti T; Gale, Robert P; Wood, William A; Hale, Gregory; Wiernik, Peter H; Hashmi, Shahrukh K; Marks, David; Ustun, Celalettin; Munker, Reinhold; Savani, Bipin N; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Kalaycio, Matt; Maziarz, Richard; Hijiya, Nobuko; Saber, Wael

    2016-06-01

    Chronic myeloid leukemia (CML) in children and young adults is uncommon. Young patients have long life expectancies and low morbidity with hematopoietic cell transplantation (HCT). Prolonged tyrosine kinase inhibitor (TKI) use may cause significant morbidity. In addition, indication for HCT in patients in the first chronic phase is not established. We hence retrospectively evaluated outcomes in 449 CML patients with early disease receiving myeloablative HCT reported to the CIBMTR. We analyzed various factors affecting outcome, specifically the effect of age and pre-HCT TKI in pediatric patients (age HCT probability rates of 5-year overall survival (OS) and leukemia-free survival (LFS) were 75% and 59%, respectively. Rates of OS and LFS were 76% and 57% in HCT TKI therapy on OS, LFS, transplant related mortality, or relapse. Favorable factors for OS were MSD (P HCT (2003 to 2010; P = .04). LFS was superior with MSD (P  90 (P = .03) compared with unrelated or mismatched peripheral blood stem cells donors and recipients with lower performance scores. Older age was associated with increased incidence of chronic graft-versus-host disease (P = .0002). In the current era, HCT outcomes are similar in young patients and children with early CML, and best outcomes are achieved with BM grafts and MSD. PMID:26964698

  14. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  15. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days −10 to −6, etoposide (VP16) on Day −5 (60 mg/kg), and cyclophosphamide (CY) on Day −3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days −12 to −8 (800 μM min), TMI on Days −8 to −4, and VP16 on Day −3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible

  16. OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    朱康儿; 张涛; 陈盛亭; 钟隽; 曾慧兰

    2004-01-01

    Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA

  17. Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

    Science.gov (United States)

    Yeshurun, Moshe; Shpilberg, Ofer; Herscovici, Corina; Shargian, Liat; Dreyer, Juliet; Peck, Anat; Israeli, Moshe; Levy-Assaraf, Maly; Gruenewald, Tsipora; Mechoulam, Raphael; Raanani, Pia; Ram, Ron

    2015-10-01

    Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT). Cannabidiol (CBD), a nonpsychotropic ingredient of Cannabis sativa, possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT. We conducted a phase II study. GVHD prophylaxis consisted of cyclosporine and a short course of methotrexate. Patients transplanted from an unrelated donor were given low-dose anti-T cell globulin. CBD 300 mg/day was given orally starting 7 days before transplantation until day 30. Forty-eight consecutive adult patients undergoing alloHCT were enrolled. Thirty-eight patients (79%) had acute leukemia or myelodysplastic syndrome and 35 patients (73%) were given myeloablative conditioning. The donor was either an HLA-identical sibling (n = 28), a 10/10 matched unrelated donor (n = 16), or a 1-antigen-mismatched unrelated donor (n = 4). The median follow-up was 16 months (range, 7 to 23). No grades 3 to 4 toxicities were attributed to CBD. None of the patients developed acute GVHD while consuming CBD. In an intention-to-treat analysis, we found that the cumulative incidence rates of grades II to IV and grades III to IV acute GVHD by day 100 were 12.1% and 5%, respectively. Compared with 101 historical control subjects given standard GVHD prophylaxis, the hazard ratio of developing grades II to IV acute GVHD among subjects treated with CBD plus standard GVHD prophylaxis was .3 (P = .0002). Rates of nonrelapse mortality at 100 days and at 1 year after transplantation were 8.6% and 13.4%, respectively. Among patients surviving more than 100 days, the cumulative incidences of moderate-to-severe chronic GVHD at 12 and 18 months were 20% and 33%, respectively. The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double-blind controlled study is warranted

  18. Effects of bone marrow mesenchymal stem cells on hematopoietic recovery and acute graft-versus-host disease in murine allogeneic umbilical cord blood transplantation model.

    Science.gov (United States)

    Li, Zhen Yu; Wang, Chun Qing; Lu, Guang; Pan, Xiu Ying; Xu, Kai Lin

    2014-09-01

    To investigate the effect of bone marrow mesenchymal stem cells (MSC) on hematopoietic recovery and acute graft-versus-host disease (GVHD) in a murine allogeneic umbilical cord blood transplantation (allo-UCBT) model. MSCs were obtained from C57/BL mouse bone marrow. The MSC phenotypes were identified by flow cytometry (FCM), and their ability to differentiate into osteoblasts and adipocytes was tested. Once murine allo-UCBT and aGVHD models were established, mice were divided into five groups: (1) total body irradiation (TBI) group, each mouse receiving 0.3 ml sterile saline infusion after TBI and used as control; (2) UCB group, receiving 2 × 10(6) umbilical cord blood mononuclear cells (UCB-MNC) after TBI; (3) UCB+MSC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(7) MSC after TBI; (4) UCB+SC group, receiving 2 × 10(6) UCB-MNC and 2 × 10(6) spleen cells after TBI; and (5) UCB+SC+MSC group, receiving 2 × 10(6) UCB-MNC, 2 × 10(7) MSC and 2 × 10(6) spleen cells after TBI. To evaluate the engraftment of HSC, the white blood cells, red blood cells, and platelets counts were tested at different time points after transplantation, and the ratio of chimerism was identified by FCM. The acute GVHD clinical scores, recipient mice survival, and the histopathological analyses were used to evaluate the effect of MSC on acute GVHD. MSCs were successfully obtained in vitro and FCM analysis showed that these cells are highly positive for CD90.2, CD44, and negative for CD34, CD45, and they are capable to differentiate into osteoblasts and adipocytes after being induced. Compared to UCB group, the UCB+MSC mice had shorter duration of myelosuppression and higher percentage of donor-derived cells which was up to 22.87 ± 4.3 % and the white blood cell (WBC), red blood cell (RBC), and platelet counts started to increase by day 6 after transplantation. Moreover, the average survival time for UCB+MSC mice was 25.0 ± 10.55 days, while for the UCB group it was 15.5 ± 12.50 days

  19. SCT Barrel Assembly Complete

    CERN Multimedia

    L. Batchelor

    As reported in the April 2005 issue of the ATLAS eNews, the first of the four Semiconductor Tracker (SCT) barrels, complete with modules and services, arrived safely at CERN in January of 2005. In the months since January, the other three completed barrels arrived as well, and integration of the four barrels into the entire barrel assembly commenced at CERN, in the SR1 building on the ATLAS experimental site, in July. Assembly was completed on schedule in September, with the addition of the innermost layer to the 4-barrel assembly. Work is now underway to seal the barrel thermal enclosure. This is necessary in order to enclose the silicon tracker in a nitrogen atmosphere and provide it with faraday-cage protection, and is a delicate and complicated task: 352 silicon module powertapes, 352 readout-fibre bundles, and over 400 Detector Control System sensors must be carefully sealed into the thermal enclosure bulkhead. The team is currently verifying the integrity of the low mass cooling system, which must be d...

  20. 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...

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

    Directory of Open Access Journals (Sweden)

    Marilène Binsfeld

    Full Text Available Multiple myeloma (MM is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD.Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor or autologous (Balb/cJ donor transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses

  2. Higher Early Monocyte and Total Lymphocyte Counts Are Associated with Better Overall Survival after Standard Total Body Irradiation, Cyclophosphamide, and Fludarabine Reduced-Intensity Conditioning Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Adults.

    Science.gov (United States)

    Le Bourgeois, Amandine; Peterlin, Pierre; Guillaume, Thierry; Delaunay, Jacques; Duquesne, Alix; Le Gouill, Steven; Moreau, Philippe; Mohty, Mohamad; Campion, Loïc; Chevallier, Patrice

    2016-08-01

    This single-center retrospective study aimed to report the impact of early hematopoietic and immune recoveries after a standard total body irradiation, cyclophosphamide, and fludarabine (TCF) reduced-intensity conditioning (RIC) regimen for double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT) in adults. We analyzed 47 consecutive patients older than 17 years who engrafted after a dUCB TCF allo-SCT performed between January 2006 and April 2013 in our department. Median times for neutrophil and platelet recoveries were 17 (range, 6 to 59) and 37 days (range, 0 to 164), respectively. The 3-year overall (OS) and disease-free survivals, relapse incidence, and nonrelapse mortality were 65.7%, 57.2%, 27.1%, and 19%, respectively. In multivariate analysis, higher day +30 monocyte (≥615/mm(3); hazard ratio [HR], .04; 95% confidence interval [CI], .004 to .36; P < .01) and day +42 lymphocyte (≥395/mm(3); HR, .16; 95% CI, .03 to .78; P = .02) counts were independently associated with better OS. These results suggest that early higher hematopoietic and immune recovery is predictive of survival after dUCB TCF RIC allo-SCT in adults. Factors other than granulocyte colony-stimulating factor, which was used in all cases, favoring expansion of monocytes or lymphocytes, should be tested in the future as part of the UCB transplantation procedure. PMID:27118570

  3. JACIE accreditation in paediatric haemopoietic SCT.

    Science.gov (United States)

    Cornish, J M

    2008-10-01

    The Joint Accreditation Committee of the International Society for Cellular Therapy (ISCT) and European Group for Blood and Marrow Transplantation (EBMT), known as JACIE, is a nonprofit body established for the purposes of assessment and accreditation in the field of haemopoietic SCT (HSCT). The committee was established in 1999 with the aim of creating a standardized system of accreditation officially recognized across Europe and based on the accreditation standards established by the US-based Foundation for the Accreditation of Cellular Therapy (FACT). The major objectives of JACIE are to improve the quality of HSCT in Europe by providing a means whereby transplant centres, cell collection facilities and processing facilities can demonstrate high-quality practice. JACIE launched its official inspection programme in January 2004, and since then more than 35 centres in Europe have been inspected. The history of paediatric-specific accreditation guidelines has lagged behind the overall development but is now incorporated within the standards. There is now acknowledgement that a paediatric transplant team will be headed by a paediatric programme director, that an independent paediatric unit will perform no less than 10 allogeneic transplants in children under the age of 18 per year, be looked after by nurses and junior doctors specifically trained in paediatric practice and have access to paediatric subspecialties with an intensive care unit on site. Paediatric units will be examined by a paediatric-trained inspector. Remaining issues of difference with the guidelines relate to the numbers required for accreditation in combined units. Overall, the paediatric community in Europe has embraced the JACIE guidelines. JACIE is working more closely with other international organizations in cellular therapy to develop international standards for all aspects of SCT. The recent implementation of Directive 2004/23/EC has provided an impetus for the implementation of JACIE in

  4. Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

    Science.gov (United States)

    Montesinos, P; Rodríguez-Veiga, R; Boluda, B; Martínez-Cuadrón, D; Cano, I; Lancharro, A; Sanz, J; Arilla, M J; López-Chuliá, F; Navarro, I; Lorenzo, I; Salavert, M; Pemán, J; Calvillo, P; Martínez, J; Carpio, N; Jarque, I; Sanz, G F; Sanz, M A

    2015-11-01

    Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment. PMID:26281032

  5. TRT and SCT barrels merge

    CERN Multimedia

    Wells, P S

    2006-01-01

    The SCT barrel was inserted in the TRT on 17 February, just missing Valentine's day. This was a change of emphasis for the two detectors. In the preceeding months there had been a lot of focus on testing their performance. The TRT had been observing cosmic rays through several sectors of the barrel, and all the modules on each of the four layers of the SCT had been characterised prior to integration. In parallel, the engineering teams, lead by Marco Olcese, Andrea Catinaccio, Eric Perrin, Neil Dixon, Iourii Gusakov, Gerard Barbier and Takashi Kohriki, had been preparing for this critical operation. Figure 1: Neil Dixon and Marco Olcese verifying the final alignment The two detectors had to be painstakingly aligned to be concentric to within a millimetre. The SCT was held on a temporary cantilever stand, and the TRT in the ID trolley had to inch over it. Finally the weight of the SCT was transferred to the rails on the inside of the TRT itself. The SCT services actually protruded a little outside the oute...

  6. Which Patients Should Undergo Allogeneic Stem Cell Transplantation for Myelodysplastic Syndromes, and When Should We Do It?

    Science.gov (United States)

    Oran, Betul

    2015-06-01

    Allogeneic hematopoietic stem cell transplantation (SCT) can cure a proportion of patients with myelodysplastic syndromes (MDS). However, treatment related toxicities, graft versus host disease, infectious complications and relapse remain major problems post transplant. Further, recent new developments with innovative drugs including hypomethylating agents (HMA) have extended the therapeutic alternatives for our patients. Nevertheless, with the introduction of reduced-intensity conditioning and thereby reducing early mortality, transplant numbers in MDS patients have significantly increased recently. In the absence of prospective randomized trials emphasis should be put on patient selection and optimization of the pre- and post-transplant treatment in order to achieve long-term disease control and at the same time maintain an adequate quality of life. With better understanding of disease biology and prognosis and with different types of conditioning regimens as well as different graft sources, a transplant strategy should be tailored to the individual host to maximize the benefits of this procedure. PMID:26297277

  7. The ATLAS semiconductor tracker (SCT)

    CERN Document Server

    Jackson, J N

    2005-01-01

    The ATLAS detector (CERN/LHCC/94-43 (1994)) is designed to study a wide range of physics at the CERN Large Hadron Collider (LHC) at luminosities up to 10**3**4 cm**-**2 s**-**1 with a bunch-crossing rate of 40 MHz. The Semiconductor Tracker (SCT) forms a key component of the Inner Detector (vol. 1, ATLAS TDR 4, CERN/LHCC 97-16 (1997); vol. 2, ATLAS TDR 5, CERN/LHCC 97-17 (1997)) which is situated inside a 2 T solenoid field. The ATLAS Semiconductor Tracker (SCT) utilises 4088 silicon modules with binary readout mounted on carbon fibre composite structures arranged in the forms of barrels in the central region and discs in the forward region. The construction of the SCT is now well advanced. The design of the SCT modules, services and support structures will be briefly outlined. A description of the various stages in the construction process will be presented with examples of the performance achieved and the main difficulties encountered. Finally, the current status of the construction is reviewed.

  8. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

    OpenAIRE

    Paulo José Lorenzoni; Rosana Herminia Scola; Ana Lucila Moreira Carsten; Ana Paula Trentin; Hélio A.G. Teive; Ricardo Pasquini; Lineu C. Werneck

    2007-01-01

    The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an unusual but important complication of hematopoietic stem cell transplantation (HSCT) rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinatin...

  9. Effect of titrated parenteral nutrition on body composition after allogeneic hematopoietic stem cell transplantation in children: a double-blind, randomized, multicenter trial123

    OpenAIRE

    Sharma, Tanvi S.; Bechard, Lori J.; Feldman, Henry A.; Venick, Robert; Gura, Kathleen; Gordon, Catherine M; Sonis, Andrew; Guinan, Eva C.; Duggan, Christopher

    2011-01-01

    Background: Children undergoing hematopoietic stem cell transplantation (HSCT) often require parenteral nutrition (PN) to optimize caloric intake. Standard approaches to nutritional supplementation provide 130–150% of estimated energy expenditure, but resting energy expenditure (REE) may be lower than expected after HSCT. Provision of PN exceeding energy needs may lead to overfeeding and associated complications.

  10. Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

    DEFF Research Database (Denmark)

    Uhlving, H H; Buchvald, F; Heilmann, C J;

    2012-01-01

    Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7-26% of the patients, with a reported mortality rate of 21-100%. It is considered a manifestation of chronic graft-versus-host disease, but our knowledge of aetiology and pathogenes...... treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.Bone Marrow Transplantation advance online publication, 29 August 2011; doi:10.1038/bmt.2011.161....

  11. Phase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.

    Science.gov (United States)

    El-Jawahri, Areej; Li, Shuli; Ballen, Karen K; Cutler, Corey; Dey, Bimalangshu R; Driscoll, Jessica; Hunnewell, Chrisa; Ho, Vincent T; McAfee, Steven L; Poliquin, Cathleen; Saylor, Meredith; Soiffer, Robert J; Spitzer, Thomas R; Alyea, Edwin; Chen, Yi-Bin

    2016-01-01

    Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. Secondary endpoints included nonrelapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS), and overall survival (OS). Thirty-four patients (acute myeloid leukemia [AML], n = 25; myelodysplastic syndromes, n = 5; and acute lymphoid leukemia, n = 4) were enrolled. Day 40+ engraftment with donor chimerism was achieved in 33 of 34 patients with 1 patient dying before count recovery. Day 100 and 1-year NRM were 5.9% (95% confidence interval [CI], 1.0 to 17.4) and 24% (95% CI, 11 to 39), respectively. The 2-year relapse rate was 26% (95% CI, 13 to 42). Cumulative incidences of acute and chronic GVHD were 21% and 44%, respectively. The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD. PMID:26260679

  12. Higher Busulfan Dose Intensity Does Not Improve Outcomes of Patients Undergoing Allogeneic Hematopoietic Cell Transplantation Following Fludarabine, Busulfan-based Reduced Toxicity Conditioning

    OpenAIRE

    Hamadani, Mehdi; Craig, Michael; Gary S Phillips; Abraham, Jame; Tse, William; Cumpston, Aaron; Gibson, Laura; Remick, Scot C.; Bunner, Pamela; Leadmon, Sonia; Elder, Patrick; Hofmeister, Craig; Penza, Sam; Efebera, Yvonne; Andritsos, Leslie

    2011-01-01

    We evaluated the impact of busulfan dose-intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30mg/m2/day, days −7 to −3), and 6mg/kg of ATG (RIC group), while 37 patients received a more-intense conditioning with busulfan (130mg/m2/day IV, days −6 to −3), fludarabine (40mg/m2/day, days...

  13. 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)

    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

  14. Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy.

    Science.gov (United States)

    Safdar, A; Papadopoulos, E B; Young, J W

    2002-12-01

    Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk. PMID:12535265

  15. Quantification by magnetic resonance imaging and liver consequences of post-transfusional iron overload alone in long term survivors after allogeneic hematopoietic stem cell transplantation (HSCT).

    Science.gov (United States)

    Rose, Christian; Ernst, Olivier; Hecquet, Bernard; Maboudou, Patrice; Renom, Pascale; Noel, Marie Pierre; Yakoub-Agha, Ibrahim; Bauters, Francis; Jouet, Jean Pierre

    2007-06-01

    We quantified and studied the impact of post transfusional iron overload alone in post allogeneic HSCT. Median number of RBCs was 18. Ferritin was 532 mg/L. Liver iron content (LIC) was 117 mmoles/gdw. Correlation RBCs and ferritin was (r=0.81); RBCs and LIC was (r=0.84). The high ferritin group differed from normal ferritin group in terms of RBCs transfused (p<10(-3)), ALT (p<0.009). But occurrence of liver dysfunction was not significant. Magnitude of iron overload correlates closely to the number of RBCs and is quantified by MRI. Impact on liver dysfunction is moderate in absence of co-morbidity. PMID:17550861

  16. Allogeneic Stem Cell Transplantation for Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Bhatt, Vijaya Raj

    2016-06-01

    Observational studies indicate a similar or higher probability of disease control, higher risk of non-relapse mortality (NRM), and similar overall survival (OS) with allogeneic stem cell transplantation (alloSCT), compared to autologous SCT, in relapsed or refractory non-Hodgkin lymphoma. Careful patient selection and utilization of reduced intensity conditioning (RIC) alloSCT may allow reduction in NRM. The optimal conditioning regimen and the roles of radioimmunotherapy, T cell depletion, and tandem SCT continue to be explored. Recent studies highlight comparable results with haploidentical SCT and cord blood SCT, thus providing alternate donor sources. Disease relapse and late effects continue to be major problems. Optimization of SCT techniques (e.g., improved graft-versus-host disease prophylaxis), post-transplant monitoring of minimal residual disease, and post-transplant maintenance, or pre-emptive therapy (e.g., with novel therapies) are emerging strategies to reduce the risk of relapse. Survivorship management using a multidisciplinary care approach, adoption of healthy lifestyle, and socioeconomic counseling are integral parts of a high-quality transplant program. PMID:26983957

  17. 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).......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)....

  18. Disseminated Bacillus Calmette-Guérin (BCG) infection following allogeneic hematopoietic stem cell transplant in a patient with Bare Lymphocyte Syndrome type II

    Science.gov (United States)

    Abu-Arja, R.F.; Gonzalez, B.E.; Jacobs, M.R.; Cabral, L.; Egler, R.; Auletta, J.; Arnold, J.; Cooke, K.R.

    2016-01-01

    We describe the first case, to our knowledge, of disseminated Mycobacterium bovis Bacillus Calmette-Guérin infection in a child with Bare Lymphocyte Syndrome type II after undergoing hematopoietic stem cell transplantation (HSCT). The patient presented 30 days post HSCT with fever and lymphadenitis. Lymph node, blood, and gastric aspirates were positive for M. bovis. The patient received a prolonged treatment course with a combination of isoniazid, levofloxacin, and ethambutol. Her course was further complicated by granulomatous lymphadenitis and otitis media associated with M. bovis that developed during immune suppression taper and immune reconstitution. Ultimately, the patient recovered fully, in association with restoration of immune function, and has completed 12 months of therapy. PMID:24995715

  19. 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.

     

  20. Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center.

    Science.gov (United States)

    Rowe, R Grant; Guo, Dongjing; Lee, Michelle; Margossian, Steven; London, Wendy B; Lehmann, Leslie

    2016-07-01

    Cytomegalovirus (CMV) infection is a significant source of morbidity and mortality in allogeneic stem cell transplantation (SCT). We identified a cohort of 91 pediatric SCT patients at risk (defined as either donor and/or recipient seropositivity) for CMV infection at our institution. We retrospectively categorized at-risk SCT recipients as those who (1) were at risk of CMV infection in the post-SCT period, (2) had documented CMV infection before SCT, (3) experienced recurrence of post-SCT CMV viremia, or (4) experienced late post-SCT CMV viremia; categories were not mutually exclusive. We analyzed the impact of SCT-related factors on incidence of CMV infection and outcome, and we described the outcome of each of these cohorts. In univariate analysis, recipient CMV seropositivity, use of umbilical cord blood graft, and acute graft-versus-host disease (GVHD) predicted post-SCT CMV viremia, and the effects of acute GVHD (odds ratio, 4.018; 95% confidence interval, 1.032 to 15.643) and CMV seropositivity (odds ratio, 16.525; 95% confidence interval, 2.041 to 133.803) were confirmed in multivariate analysis. Patients with recurrence of post-SCT CMV viremia had a 50% all-cause mortality rate, compared with 12% in all 91 patients. Patients with pre-SCT CMV infection had a high incidence of post-SCT CMV infection but could successfully undergo SCT with antiviral prophylaxis and pre-emptive CMV treatment. All patients with late CMV infection had prior GVHD. Theses findings identify risk factors for post-SCT CMV infection and provide novel descriptions of childhood SCT recipients with pre-SCT, recurrent, and late CMV infection, which may contribute to risk stratification strategies for CMV at-risk patients in pediatric allogeneic SCT. PMID:27090959

  1. Idarubicin-intensified BUCY2 conditioning regimen improved survival in high-risk acute myeloid, but not lymphocytic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: A retrospective comparative study.

    Science.gov (United States)

    Fang, Jun; Zhang, Ran; Wang, Huafang; Hong, Mei; Wu, Qiuling; Nie, Dimin; You, Yong; Zhong, Zhaodong; Li, Weiming; Hu, Yu; Xia, Linghui

    2016-07-01

    The intensity of conditioning regimen is highly correlated with outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported that idarubicin (IDA) intensified BUCY2 regimen could reduce relapse and improve survival for high-risk hematological malignancies undergoing allo-HSCT. However, there is no published study comparing the efficacy of IDA-BUCY2 regimen for high-risk acute myeloid leukemia (AML) versus acute lymphocytic leukemia (ALL). We further retrospectively compared therapeutic outcomes of intensified conditioning regimen on 140 high-risk AML and ALL patients in the data analyses. IDA 15mg/m(2)/d was administered by continuous infusion from day -11 to -9, followed by intravenous injection of busulfan (BU) (3.2mg/kg/d) from day -6 to -4, and intravenous injection of cyclophosphamide (CY) (1.8g/m(2)/d) from day -3 to -2 in IDA-BUCY2 regimen. For high-risk AML, cumulative probabilities of 3-year relapse rates in IDA-BUCY2 and traditional BUCY2 regimens were 16.9%, 43.3% (P=0.016). Cumulative probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 69.2% vs 44.0% (P=0.024), and 66.9% vs 38.2% (P=0.01). However, two regimens showed no significant differences for high-risk ALL. Multivariate analysis also indicated that IDA intensified BUCY2 conditioning was the favorable variable to reduce relapse and elevate survival for high-risk AML patients. In conclusion, IDA-BUCY2 regimen reduces relapse and improves survival for high-risk AML undergoing allo-HSCT, but not presenting uniform therapeutic effects for high-risk ALL. PMID:27131062

  2. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material. PMID:26040247

  3. HHV-6 encephalitis may complicate the early phase after allogeneic hematopoietic stem cell transplantation: Detection by qualitative multiplex PCR and subsequent quantitative real-time PCR.

    Science.gov (United States)

    Inazawa, Natsuko; Hori, Tsukasa; Yamamoto, Masaki; Hatakeyama, Naoki; Yoto, Yuko; Nojima, Masanori; Yasui, Hiroshi; Suzuki, Nobuhiro; Shimizu, Norio; Tsutsumi, Hiroyuki

    2016-02-01

    Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post-HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first-line screening test and real-time PCR for subsequent quantitative evaluation. Five hundred ninety-one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV-6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV-7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV-6 DNA levels demonstrated four of the six HHV-6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV-6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV-6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV-6 encephalitis can be improved by confirming high HHV-6 DNA load in blood. PMID:26241219

  4. Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution

    Directory of Open Access Journals (Sweden)

    C.R. de Medeiros

    2006-10-01

    Full Text Available We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15; group 2, unrelated cord blood (N = 17, and group 3, related non-sibling bone marrow (N = 15. Twenty-four patients (51% had complete engraftment, which was not influenced by gender (P = 0.87, age (P = 0.45, dose of cyclophosphamide (P = 0.80, nucleated cell dose infused (P = 0.60, or use of anti-T serotherapy (P = 0.20. Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007 and use of a fludarabine-based conditioning regimen (P = 0.046. Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011 and degree of HLA disparity (P = 0.007. Intensity of mucositis (P = 0.50 and use of androgen prior to transplant had no influence on survival (P = 0.80. Acute graft-versus-host disease (GVHD grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at ~8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with <25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present seeking for a related non-sibling donor is highly recommended.

  5. Sibling versus Unrelated Donor Allogeneic Hematopoietic Cell Transplantation for CML: Refined HLA-matching shows more GVHD but not less relapse

    Science.gov (United States)

    Weisdorf, Daniel J.; Nelson, Gene; Lee, Stephanie J; Haagenson, Michael; Spellman, Stephen; Antin, Joseph H; Bolwell, Brian; Cahn, Jean-Yves; Cervantes, Francisco; Copelan, Edward; Gale, Robert; Gratwohl, Alois; Khoury, H. Jean; McCarthy, Philip; Marks, David I; Szer, Jeff; Woolfrey, Ann; Cortes-Franco, Jorge; Horowitz, Mary M; Arora, Mukta

    2010-01-01

    Purpose Unrelated donor (URD) hematopoietic cell transplantation (HCT) can eradicate chronic myelogenous leukemia (CML). It has been postulated that greater donor:recipient-histoincompatibility can augment the graft vs. leukemia (GvL) effect. We previously reported similar, but not equivalent outcomes of URD vs. sibling donor HCT for CML using an older, less precise classification of HLA-matching. Methods Our recently refined HLA-matching classification, suitable for interpretation when complete allele-level typing is unavailable was used to reanalyze outcomes of previous HCT for CML. Results We observed that new matching criteria identifies substantially more frequent mismatch than older, less precise “6 of 6 antigen” matched URD-HCT. Only 37% of those previously called “HLA-matched” were HLA-well-matched in new classification and 44% were partially-matched. The refined matching classification confirmed that partially matched or mismatched URD:recipient pairs have significantly greater risks of graft failure compared to either sibling or well-matched URD-HCT. Acute and chronic GVHD are significantly more frequent with all levels of recategorized URD HLA-matching. Importantly, survival and leukemia-free survival remain significantly worse following URD-HCT at any matching level. No augmented GvL effect accompanied URD HLA-mismatch. Compared to sibling donor transplants, we observed marginally increased, but not significantly different risks of relapse in either well-matched, partially-matched or mismatched URD-HCT. Conclusions These data confirm the utility of our revised HLA-matching schema as applicable for analysis of retrospective data sets when fully informative, allele level-typing is unavailable. In this analysis, greater histoincompatibility can augment GVHD but does not improve protection against relapse thus the best donor is still the most closely matched. PMID:19822308

  6. Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Chen, Yun; Kornblit, Brian; Hamlin, Donald K; Sale, George E; Santos, Erlinda B; Wilbur, D Scott; Storer, Barry E; Storb, Rainer; Sandmaier, Brenda M

    2012-02-01

    To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 ((211)At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with (211)At doses less than or equal to 405 μCi/kg. Higher doses of (211)At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest (211)At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with (211)At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning. PMID:22134165

  7. 亲属单倍型与同胞全相合HSCT后巨细胞病毒感染临床特点的比较%Comparative study on clinical features of cytomegalovirus infection after allogenic hematopoietic stem cell transplantation from HLA haploidentical related donors vs HLA-matched sibling donors

    Institute of Scientific and Technical Information of China (English)

    黄金菊; 陆晓茜; 闫晨华; 赵晓甦; 许兰平; 黄晓军; 刘代红

    2013-01-01

    Objective To compare the clinical features of cytomegalovirus (CMV) infection and CMV disease after allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA haploidentical related doors vs.HLA-matched sibling donors.Methods A total of 327 patients who received allogeneic HSCT from Jan.2011 to Dec.2011 were enrolled.There were 312 patients who had complete serological data before HSCT including 216 cases of HLA haploidentical related HSCT and 96 cases of HLA-matched sibling HSCT.Monitoring of CMV antigenemia was performed by using real-time quantitative (RQ) PCR after transplantation.Risk factors were compared by univariate and multivariate analysis.Results The cumulative incidence of CMV infection and CMV disease was (80.1 ± 2.7) % and (8.7 ± 2.0) % in HLA haploiddentical HSCT group,and (21.1 ± 4.9) % and 0 in HLA-matched sibling HSCT group respectively,and the difference was statistically significant between the two groups (P<0.01).Univariate analysis revealed that HLA haploidentical related HSCT,less than 20 years of age,high risk disease,CMV-IgG serum positivity in patients or donors,acute graft-versus-host disease (aGVHD),EB viremia,and hemorrhagic cystitis were the risk factors of CMV infection.HLA haploidentical related SCT and hemorrhagic cystitis were the risk factors for CMV disease.Multivariate analysis showed that patients less than 20 years of age had a significantly high incidence of CMV infection.Patients from HLA-matched sibling HSCT,low risk disease,aGVHD,hemorrhagic cystitis had a significantly low incidence of CMV infection.Conclusion Compared with patients receiving HLA-matched sibling HSCT,those who received HLA haploidentical related HSCT had significantly high incidence of CMV infection and CMV disease,which were correlated with incidence of hemorrhagic cystitis.%目的 比较亲属单倍型与同胞全相合异基因造血干细胞移植(HSCT)受者巨细胞病毒(CMV)感染及CMV病的临床特点.方法 2011年1-12

  8. 异基因造血干细胞移植治疗急性髓系白血病的现状%Allogeneic hematopoietic stem cell transplantation in treatment of acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    符粤文; 王倩; 宋永平

    2013-01-01

    异基因造血干细胞移植(allo-HSCT)是治疗急性髓系白血病(AML)的有效方法之一.allo-HSCT的治疗作用来自于预处理中的放疗和(或)化疗,以及供者免疫系统的移植物抗白血病(GVL)效应.近十年来,随着对白血病细胞生物学特性研究的不断深入,根据细胞遗传学和分子标志对AML进行危险程度分级,使我们能够挑选出哪些AML患者可以从allo-HSCT中获益.allo-HSCT治疗AML的临床疗效已有明显提高,并且适用范围也较前扩大,但在AML中的应用还存在一定差异.现对allo-HSCT治疗AML的机制、时机、疗效、供者选择及预处理方案进行讨论.%Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective way to acute myeloid leukemia (AML).The therapy effect of allo-HSCT comes from the preconditioning of the radiation and/or chemotherapy,as well as the graft versus leukemia (GVL) effect of the donor' s immune system.In nearly a decade,with the deepening research on biological characteristics of leukemia cells,according to the cytogenetic and molecular markers to dangerous degree classification of AML,which enables us to pick out AML patients can benefit from allo-HSCT.The clinical curative effect of allo-HSCT for AML has obviously improved,and applicable scope has also extended,but there are some differences in the application of AML.The mechanism,opportunity,curative effects,donor selection and preconditioning of allo-HSCT for AML are discussed.

  9. Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Kharfan-Dabaja Mohamed A

    2013-01-01

    Full Text Available Abstract Background Despite advances in understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM and availability of more effective therapies, MM remains incurable. The autologous-allogeneic (auto-allo hematopoietic cell transplantation (HCT strategy is based on combining cytoreduction from high-dose (chemo- or chemoradio-therapy with adoptive immunotherapy. However, conflicting results have been reported when an auto-allo HCT approach is compared to tandem autologous (auto-auto HCT. A previously published meta-analysis has been reported; however, it suffers from serious methodological flaws. Methods A systematic search identified 152 publications, of which five studies (enrolling 1538 patients met inclusion criteria. All studies eligible for inclusion utilized biologic randomization. Results Assessing response rates by achievement of at least a very good partial response did not differ among the treatment arms [risk ratio (RR (95% CI = 0.97 (0.87-1.09, p = 0.66]; but complete remission was higher in the auto-allo HCT arm [RR = 1.65 (1.25-2.19, p = 0.0005]. Event-free survival did not differ between auto-allo HCT group versus auto-auto HCT group using per-protocol analysis [hazard ratio (HR = 0.78 (0.58-1.05, p = 0.11] or using intention-to-treat analysis [HR = 0.83 (0.60-1.15, p = 0.26]. Overall survival (OS did not differ among these treatment arms whether analyzed on per-protocol [HR = 0.88 (0.33-2.35, p = 0.79], or by intention-to-treat [HR = 0.80 (0.48-1.32, p = 0.39] analysis. Non-relapse mortality (NRM was significantly worse with auto-allo HCT [RR (95%CI = 3.55 (2.17-5.80, p  Conclusion Despite higher complete remission rates, there is no improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. At present, totality of evidence suggests that an auto-allo HCT approach for patients with newly diagnosed

  10. Reduced-Intensity Conditioning with Fludarabine, Cyclophosphamide, and High-Dose Rituximab for Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma: A Phase Two Multicenter Trial from the Blood and Marrow Transplant Clinical Trials Network.

    Science.gov (United States)

    Laport, Ginna G; Wu, Juan; Logan, Brent; Bachanova, Veronika; Hosing, Chitra; Fenske, Timothy; Longo, Walter; Devine, Steven M; Nademanee, Auayporn; Gersten, Iris; Horowitz, Mary; Lazarus, Hillard M; Riches, Marcie L

    2016-08-01

    Allogeneic (allo) hematopoietic cell transplantation (HCT) can induce long-term remissions in chemosensitive relapsed follicular lymphoma (FL). The Blood and Marrow Transplant Clinical Trials Network conducted a multicenter phase 2 trial to examine the efficacy of alloHCT using reduced-intensity conditioning with rituximab (RTX) in multiply relapsed, chemosensitive FL. The primary endpoint was 2-year progression-free survival (PFS). The conditioning regimen consisted of fludarabine, cyclophosphamide, and high-dose RTX (FCR), in which 3 of the 4 doses of RTX were administered at a dose of 1 gm/m(2). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus and methotrexate. Sixty-five patients were enrolled and 62 were evaluable. Median age was 55 years (range, 29 to 74). This group was heavily pretreated: 77% had received ≥ 3 prior regimens, 32% had received ≥ 5 prior regimens, and 11% had received prior autologous HCT. Donors were HLA-matched siblings (n = 33) or HLA-matched unrelated adults (n = 29). No graft failures occurred. The overall response rate after HCT was 94% with 90% in complete remission (CR), including 24 patients not in CR before alloHCT. With a median follow-up of 47 months (range, 30 to 73), 3-year PFS and overall survival rates were 71% (95% confidence interval, 58% to 81%) and 82% (95% confidence interval, 70% to 90%), respectively. Three-year cumulative incidences of relapse/progression and nonrelapse mortality were 13% and 16%, respectively. Two-year cumulative incidences of grades 2 to 4 and grades 3 or 4 acute GVHD were 27% and 10%, respectively, and extensive chronic GVHD incidence was 55%. Serum RTX concentrations peaked at day +28 and remained detectable as late as 1 year in 59% of patients with available data. In conclusion, alloHCT with FCR conditioning confers high CR rates, a low incidence of relapse/progression, and excellent survival probabilities in heavily pretreated FL patients. PMID:27118571

  11. Allogeneic cellular immunotherapy for chronic B-cell leukemia

    OpenAIRE

    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 graft-versus-leukemia (GvL) effect. However, effectiveness of this therapy is limited due to low immunogenicity of leukemic cells and the lack of specificity resulting in concurrent development of graft-versus...

  12. Ocular Graft Versus Host Disease Following Allogeneic Stem Cell Transplantation: A Review of Current Knowledge and Recommendations

    OpenAIRE

    Nariman Nassiri; Medi Eslani; Nekoo Panahi; Shiva Mehravaran; Alireza Ziaei; Djalilian, Ali R.

    2013-01-01

    Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). Ocular GVHD develops in approximately 40-60% of patients following allo-SCT and its most common clinical manifestations include keratoconjunctivitis sicca and cicatricial conjunctivitis. Ocular GVHD may lead to severe ocular surface disease, which can significantly diminish quality of life and restrict daily activities. It is thus important to monitor the condition closely since with ...

  13. Pretransplant C-reactive protein as a prognostic marker in allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Jordan, Karina Kwi Im; Christensen, Ib Jarle; Heilmann, Carsten; Sengeløv, Henrik; Müller, Klaus Gottlob

    2014-01-01

    We evaluated the prognostic role of baseline levels of C-reactive Protein (CRP) as well as CRP levels during conditioning in patients undergoing myeloablative allogeneic stem cell transplantation (SCT). Furthermore, we studied the impact of baseline clinical factors and conditioning regimens on CRP...

  14. Radiologically guided fine needle lung biopsies in the evaluation of focal pulmonary lesions in allogeneic stem cell transplant recipients.

    Science.gov (United States)

    Jantunen, E; Piilonen, A; Volin, L; Ruutu, P; Parkkali, T; Koukila-Kähkölä, P; Ruutu, T

    2002-02-01

    Lung problems are common in allogeneic stem cell transplant (SCT) recipients. To evaluate the feasibility and diagnostic yield of radiologically guided fine needle lung biopsy (FNLB) in allogeneic SCT recipients with focal pulmonary lesions, a retrospective analysis was carried out. Between 1989 and 1998, radiologists performed a total of 30 FNLBs in 21 allogeneic SCT recipients, guided either by ultrasound (n = 17) or computed tomography (n = 13). The median time from SCT to the first FNLB was 131 days (20-343 days). Prophylactic platelet transfusions were given in 19 procedures (66%). The complications of FNLB included clinically insignificant pneumothorax in four procedures (13%) and self-limiting haemoptysis in one case (3%). The first FNLB was suggestive of invasive pulmonary aspergillosis (IPA) in five patients (24%). Additional clinically useful findings of FNLB included Pseudomonas (two patients) and Nocardia (one patient). The final diagnosis of pulmonary lesions was IPA in 14 patients, immunological lung problems in four patients and other in three patients. Radiologically guided FNLB is feasible in allogeneic SCT recipients and has a low complication rate. The diagnostic yield is high especially for IPA. PMID:11896433

  15. Cellular therapy following allogeneic stem-cell transplantation

    OpenAIRE

    Rager, Alison; Porter, David L.

    2011-01-01

    Allogeneic hematopoietic stem-cell transplantation (HSCT) is the most effective approach for many patients with hematologic malignancies. Unfortunately, relapse remains the most common cause of death after allogeneic HSCT, and the prognosis of relapsed disease is poor for most patients. Induction of a graft-versus-leukemia (GVL), or graft-versus-tumor, effect through the use of donor leukocyte infusion (DLI), or donor lymphocyte infusion, has been remarkably successful for relapsed chronic my...

  16. APPLICATION OF TWO-COLOR INTERPHASE FISH USING SEX PROBE IN ALLOGENEIC STEM CELL TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    曾慧兰; 李建勇; 朱康儿; 薛永权; 李杨秋; 刘晓力; 过宇

    2002-01-01

    Objective: To evaluate the significance of two-color interphase fluorescence in situ hybridization (FISH) using X and Y centromere probe in the engraftment estimation and minimal residual disease (MRD) monitoring after allogeneic stem cell transplantation (alloSCT). Methods: Samples from 12 cases patients in different periods after alloSCT were detected by interphase FISH. Results: All of the 12 patients were proved to obtain engraftment 22(35 days after alloSCT. While traditional karyotype showed as 100%XX or 100%XY invariably, FISH showed different percentages of donor original sex chromosome. Conclusion: Two-color interphase FISH is a more sensitive and simple test for engraftment evaluation and MRD monitoring post SCT, though, it can not entirely replace traditional karyotype analysis and gene detection by RT-PCR.

  17. [Successful treatment of an overwhelming infection with granulocyte transfusion in severe aplastic anemia patient undergoing allogeneic peripheral blood stem cell transplantation].

    Science.gov (United States)

    Kazuma, Yasuhiro; Ono, Yuichiro; Yonetani, Noboru; Imai, Yukihiro; Kawakami, Manabu; Hashimoto, Hisako; Ishikawa, Takayuki

    2016-04-01

    A 19-year-old woman complaining of fever and a sore throat was diagnosed with very severe aplastic anemia (AA) by bone marrow examination at a local hospital. Despite administration of antibiotics and granulocyte-colony stimulating factor to treat the soft tissue infection in her neck, her neutrophil count showed no increase. Because emergent allogeneic stem cell transplantation (SCT) was necessary, she was referred to our hospital. On admission, computed tomography revealed right-sided severe pharyngitis and lymphadenitis causing tracheal stenosis, and emergent intubation was required the next day. Granulocyte transfusion therapy (GTX) from related donors coupled with broad-spectrum antibiotic administration controlled the otherwise overwhelming infection. The patient received allogeneic peripheral blood SCT using a reduced-intensity conditioning regimen. After allogeneic SCT, successful engraftment was obtained. She was discharged from the hospital 59 days after allogeneic SCT. She remains alive and well, as of the latest follow up. This case clearly demonstrates that GTX is useful for controlling severe infection and enables patients with severe AA to receive allogeneic SCT safely. PMID:27169447

  18. Who is fit for allogeneic transplantation?

    OpenAIRE

    Deeg, H. Joachim; Sandmaier, Brenda M.

    2010-01-01

    The use of allogeneic hematopoietic cell transplantation (HCT) has expanded progressively, facilitated by the increasing availability of unrelated donors and cord blood, and the inclusion of older patients as transplantation candidates. Indications remain diagnosis-dependent. As novel nontransplantation modalities have been developed concurrently, many patients come to HCT only when no longer responding to such therapy. However, patients with refractory or advanced disease frequently relapse ...

  19. Allogeneic hematopoietic stem cell transplantation for primary myelodysplastic syndrome Transplante alogênico de células progenitoras hematopoiéticas para síndrome mielodisplásica primária

    Directory of Open Access Journals (Sweden)

    Carlos R. Medeiros

    2004-01-01

    Full Text Available Characteristics and outcomes of 52 patients with myelodysplastic syndrome (MDS who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT were analyzed. Median age was 30 years (range 2-61 years and median time from diagnosis to allo-HSCT was 10 months (range 1-161 months. Thirty-six patients had advanced MDS or acute myeloid leukemia following MDS at transplant. Conditioning with busulfan and cyclophosphamide was administered to 73% of patients, and the median value of graft dose was 2.595 x 10(8 of total nucleated cells/kg. Overall survival and disease free survival at 4 years were 36% and 33%, respectively. Nineteen patients were alive, with a median follow-up of 3.8 years. Twelve patients relapsed and only one is alive, after donor lymphocyte infusion. Interval II occurred in 19 patients. Donor type (identical related versus non-related/partially matched related influenced the incidence of acute GVHD (P = 0.03. Eleven patients developed chronic GVHD and previous acute GVHD was a risk factor (P = 0.03. Thirty-three patients died, 22 (67% secondary to transplant-related complications. Patients with MDS should undergo allo-HSCT earlier, mainly if they have a compatible donor and are young.Características e resultados de 52 pacientes com síndrome mielodisplásica (MDS submetidos a transplante alogênico de células progenitoras hematopoiéticas (TCPH foram analisados. A idade mediana foi de 30 anos (variação de 2-61 anos e o tempo mediano entre o diagnóstico e transplante foi de dez meses (variação de 1-161 meses. Trinta e seis pacientes tinham MDS avançada ou leucemia mielóide aguda secundária a MDS ao transplante. O condicionamento com busulfano e ciclo­fosfamida foi recebido por 73% dos pacientes, e a dose celular mediana do enxerto foi de 2.56 x 10(8 células nucleadas/kg. A sobrevida global e a sobrevida livre de doença aos quatro anos foi de 36% e 33%, respectivamente. Dezenove pacientes estavam vivos, com um

  20. Tackling mantle cell lymphoma (MCL: Potential benefit of allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Satish Shanbhag

    2010-07-01

    Full Text Available Satish Shanbhag1,2, Mitchell R Smith1, Robert VB Emmons21Department of Medical Oncology, Fox Chase Cancer Center, 2Division of Bone Marrow Transplantation, Temple University, Philadelphia, PA, USAAbstract: Mantle cell lymphoma (MCL is a type of non-Hodgkins lymphoma (NHL associated with poor progression-free and overall survival. There is a high relapse rate with conventional cytotoxic chemotherapy. Intensive combination chemotherapy including rituximab, dose intense CHOP- (cyclophosphamide-doxorubicin-vincristine-prednisone like regimens, high dose cytarabine, and/or consolidation with autologous stem cell transplant (autoSCT have shown promise in significantly prolonging remissions. Data from phase II studies show that even in patients with chemotherapy refractory MCL, allogeneic stem cell transplant (alloSCT can lead to long term disease control. Most patients with MCL are not candidates for myeloablative alloSCT due to their age, comorbidities, and performance status. The advent of less toxic reduced intensity conditioning (RIC regimens, which rely more on the graft-versus-lymphoma (GVL effect, have expanded the population of patients who would be eligible for alloSCT. RIC regimens alter the balance of toxicity and efficacy favoring its use. Treatment decisions are complicated by introduction of novel agents which are attractive options for older, frail patients. Further studies are needed to determine the role and timing of alloSCT in MCL. Currently, for selected fit patients with chemotherapy resistant MCL or those who progress after autoSCT, alloSCT may provide long term survival.Keywords: mantle cell lymphoma, allogeneic SCT, nonmyeloablative, GVL

  1. Clinical Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin's Lymphoma First Autologous Stem Cell transplant Relapse%异基因造血干细胞移植治疗首例自体移植复发霍奇金淋巴瘤的临床分析

    Institute of Scientific and Technical Information of China (English)

    郭智; 陈惠仁; 刘晓东; 楼金星; 何学鹏

    2012-01-01

    目的 探讨霍奇金淋巴瘤自体移植复发后行异基因造血干细胞2次移植的可能性和安全性.方法 对1例10年前行自体造血干细胞移植复发的霍奇金淋巴瘤患者,行异基因造血干细胞移植,供者为患者母亲,采用外周血干细胞移植,预处理方案采用氟达拉滨+马法兰+兔抗人淋巴细胞免疫球蛋白,预防移植物抗宿主病采用环孢素A、霉酚酸酯、甲氨蝶呤,输注单个核细胞数14.03×108/kg,CD34+细胞6.57×106/kg.结果 2次移植后移植物成功植入,形成完全供者来源造血,移植后第20天骨髓初步植活,造血功能恢复后患者出现皮肤植物抗宿主病,FISH嵌合状态供者细胞植入率为100%,随访至今一直长期无病生存.结论 异基因造血干细胞移植,可有效治疗自体移植复发的霍奇金淋巴瘤,是安全有效的挽救治疗措施.%To investigate the possibility and security of Hodgkin s lymphoma with autologous transplantation relapse treated with allogeneic hematopoietic stem cell transplantation for the second time . Methods A case of autologous hema -topoietic stem cell transplant relapse of Hodgkin s lymphoma patients first treated 10 years ago was treated with allogeneic hemato -poietic stem cell transplantation , donor was the patient s mother, using blood stem cell transplantation , conditioning regimen was fu- dalabin Melphalan anti -THmocyte globulin. Prevention of graft -versus-host disease with cyclosporin A , mycophenolate mofetil, methotrexate. Infusion of the mononuclear cell 14.03 ×108 /kg,CD34+ cells 6. 57 × 106 /kg. Results The second post-transplant graft was successfully implanted to form a complete source of donor hematopoietic and immune function after second hematopoietic stem cell transplantation. Patients had skin graft-versus-host disease after hematopoietic recovery ,20 days later the second transplant of bone marrow preliminary engraftment and follow -up has been a long-term disease-free survival

  2. Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Derlin, Thorsten [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Hanover Medical School, Department of Nuclear Medicine, Hanover (Germany); Laqmani, Azien; Adam, Gerhard; Bannas, Peter [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Veldhoen, Simon [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); University Medical Center Wuerzburg, Department of Diagnostic and Interventional Radiology, Wuerzburg (Germany); Apostolova, Ivayla [Otto-von-Guericke University, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Ayuk, Francis; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

    2015-05-01

    To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (r{sub s} =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. (orig.)

  3. Magnetic resonance enterography for assessment of intestinal graft-versus-host disease after allogeneic stem cell transplantation

    International Nuclear Information System (INIS)

    To determine the diagnostic performance of MR enterography (MRE) for detection and grading of gastrointestinal graft-versus-host disease (GI GvHD) after hematopoietic stem cell transplantation (SCT). Forty-one patients with known GvHD or suspected GvHD underwent MRE and GI endoscopy with multi-level biopsies. MRE images were reviewed for presence of intestinal wall inflammation. Clinical grading of GI GvHD was performed. Histopathological evaluation (HPE) served as the reference standard. Overall, MRE demonstrated a per-patient sensitivity of 81.5 % for detection of GI GvHD. The most common findings were intestinal wall thickening (81.5 % of GvHD patients), luminal stenosis (81.5 %), mural contrast enhancement (70.4 %), and ascites (59.3 %). These findings were also observed in other conditions than GvHD. The most frequently involved intestinal segment was the sigmoid colon (63.0 %), followed by the ileum (59.3 %) and the jejeunum (51.9 %). The number of involved segments (rs =0.54, p =0.009) correlated significantly with clinical severity as determined by GvHD grading. After allogeneic stem cell transplantation, MRE may (1) contribute to detection and localization of GI GvHD, and (2) add information indicating the clinical severity of disease, but findings are unspecific. False negative results may be observed not only in low-grade GI GvHD. (orig.)

  4. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  5. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  6. Immunoselection techniques in hematopoietic stem cell transplantation.

    Science.gov (United States)

    Li Pira, Giuseppina; Biagini, Simone; Cicchetti, Elisabetta; Merli, Pietro; Brescia, Letizia Pomponia; Milano, Giuseppe Maria; Montanari, Mauro

    2016-06-01

    Hematopoietic Stem Cells Transplantation (HSCT) is an effective treatment for hematological and non-hematological diseases. The main challenge in autologous HSCT is purging of malignant cells to prevent relapse. In allogeneic HSCT graft-versus-host disease (GvHD) and opportunistic infections are frequent complications. Two types of graft manipulation have been introduced: the first one in the autologous context aimed at separating malignant cells from hematopoietic stem cells (HSC), and the second one in allogeneic HSCT aimed at reducing the incidence of GvHD and at accelerating immune reconstitution. Here we describe the manipulations used for cell purging in autologous HSCT or for T Cell Depletion (TCD) and T cell selection in allogeneic HSCT. More complex manipulations, requiring a Good Manufacturing Practice (GMP) facility, are briefly mentioned. PMID:27209628

  7. Molecular remission after myeloablative allogeneic stem cell transplantation predicts a better relapse-free survival in patients with multiple myeloma

    NARCIS (Netherlands)

    Corradini, P; Cavo, M; Lokhorst, H; Martinelli, G; Terragna, C; Majolino, [No Value; Valagussa, P; Boccadoro, M; Samson, D; Bacigalupo, A; Russell, N; Montefusco, [No Value; Voena, C; Gahrton, G

    2003-01-01

    Patients in complete clinical remission after myeloablative allogeneic stem cell transplantation (allo-SCT) were enrolled in a longitudinal study to assess the predictive value of molecular monitoring. Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to ge

  8. 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...

  9. 异基因造血干细胞移植治疗母细胞性浆细胞样树突细胞肿瘤%Allogeneic hematopoietic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasms

    Institute of Scientific and Technical Information of China (English)

    周红升; 许娜; 孙竞; 邓永键; 江千里; 余国攀; 刘启发

    2012-01-01

    Objective To investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with intensified conditioning regimen followed by rapidly tapering immunosuppressants and sequential minimal residual disease (MRD)-guided donor lymphocyte infusion (DLI) post-transplantation on outcome of blastic plasmacytoid dendritic cell neoplasm (BPDCN).Methods Two cases of BPDCN from January 2009 to May 2011 in Nanfang hospital were diagnosed according to 2008 WHO classification of tumours of haematopoietic and lymphoid tissues.Case 1 initially presented with typical cutaneous involvement and was promptly diagnosed with CD+4CD+56LCA+TdT+CD+43 BPDCN by skin biopsy.Case 2 was recognized as acute lymphocyte leukemia and acute non-lymphocytic leukemia,which was diagnosed to BPDCN at recurrence through flow cytometry analysis.Total-body-irradiation plus cyclophosphamide based intensified conditioning regimen were followed by allo-HSCT from sibling donor.Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate.Anti-thymocyteglobulin was included additionally for haploid donor allo-HSCT.Multi-color labeling flow cytometry was performed to monitor MRD.Rapidly tapering of prophylactic immunosuppressants and sequential MRD-guided donor lymphocyte infusion (DLI) were performed to control relapse of primary malignancy.Results Two cases of BPDCN received allo-HSCT from sibling donor after intensified conditioning regimen.Both patients achieved complete remission and complete donor engraftment.Case 1 survived refractory acyclovir-resistant Epstein-Barr virus viremia benefiting from preemptive treatment with rituximab and DLI-induced grade Ⅳ acute GVHD,but died of thrombotic microangiopathy mixed with diffuse alveolar hemorrhage and sepsis on +243 days.Case 2 relapsed just 2 months after allo-HSCT despite DLI and rapidly tapering of CsA,died of sepsis followed by diffuse intravascular coagulation on +101 days.Conclusion BPDCN is

  10. Graft-versus-leukemia effects associated with detectable Wilms tumor-1–specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia

    OpenAIRE

    Rezvani, Katayoun; Yong, Agnes S.M.; Savani, Bipin N.; Mielke, Stephan; Keyvanfar, Keyvan; Gostick, Emma; Price, David A; Douek, Daniel C.; Barrett, A. John

    2007-01-01

    To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8+ T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)–A*0201–positive ALL patients during the early phase of immune recovery after SCT (days 30-120). Seven of 10 patients had detectable WT1 expression in their peripheral blood (PB) before SCT by quantitative rev...

  11. Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation

    OpenAIRE

    Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H.; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H. Joachim

    2014-01-01

    A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patien...

  12. Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT

    DEFF Research Database (Denmark)

    Holm, A M; Riise, Gerdt; Hansson, Leif Helmuth;

    2013-01-01

    Chronic GVHD (cGVHD) associated bronchiolitis obliterans syndrome (BOS) is a serious complication after allo-SCT, and lung transplantation (LTx) may be the ultimate treatment option. To evaluate this treatment, data on all patients with LTx after allo-SCT ever performed in Sweden, Norway, Denmark...... to cGVHD after allo-SCT.Bone Marrow Transplantation advance online publication, 15 October 2012; doi:10.1038/bmt.2012.197.......Chronic GVHD (cGVHD) associated bronchiolitis obliterans syndrome (BOS) is a serious complication after allo-SCT, and lung transplantation (LTx) may be the ultimate treatment option. To evaluate this treatment, data on all patients with LTx after allo-SCT ever performed in Sweden, Norway, Denmark...

  13. Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report Polirradiculoneuropatia desmielinizante inflamatória crônica na doença do enxerto contra o hospedeiro após transplante de células hematopoiéticas alogênicas: relato de caso

    Directory of Open Access Journals (Sweden)

    Paulo José Lorenzoni

    2007-09-01

    Full Text Available The chronic inflammatory demyelinating polyradiculoneuropathy (CIDP is an unusual but important complication of hematopoietic stem cell transplantation (HSCT rarely reported to date. We describe a 17-year-old woman with a diagnosis of acute myeloid leukemia due to Fanconi's anemia who was submitted to allogeneic HSCT and developed CIDP as part of graft-versus-host disease. Investigation showed high cerebrospinal fluid protein; electrophysiological studies revealed sensory-motor demyelinating polyradiculoneuropathy; muscle and nerve biopsy were compatible with CIDP.A polirradiculoneuropatia desmielinizante inflamatória crônica (CIDP é uma incomum, porém, importante complicação do transplante de células hematopoiéticas (HSCT raramente relatada até a data. Nós descrevemos uma mulher de 17 anos com diagnóstico de leucemia mielóide aguda por anemia de Fanconi que foi submetida à HSCT e desenvolveu CIDP como parte da doença do enxerto contra o hospedeiro. A investigação mostrou elevação na proteína no líquor; estudo eletrofisiológico revelando polirradiculoneuropatia desmielinizante sensitivo-motora; e biópsia de músculo e nervo compatível com CIDP.

  14. Allogeneic Stem Cell Transplantation for Patients with T315I BCR-ABL Mutated Chronic Myeloid Leukemia.

    Science.gov (United States)

    Xu, Lan-Ping; Xu, Zheng-Li; Zhang, Xiao-Hui; Chen, Huan; Chen, Yu-Hong; Han, Wei; Chen, Yao; Wang, Feng-Rong; Wang, Jing-Zhi; Wang, Yu; Yan, Chen-Hua; Mo, Xiao-Dong; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-06-01

    Allogeneic stem cell transplantation (SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We report the outcome of SCT in 22 patients with T315I(+) CML, most (n = 16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn). The cumulative incidence of grades III to IV acute graft-versus-host disease was 9.1%. Chronic graft-versus-host disease was observed in 60.0% of patients, including 25.0% who suffered from severe disease. Four patients died of transplant-related complications at a median interval from SCT of 16.3 months. The estimated 2-year leukemia-free survival rate was 80.0%, 72.9%, and 0% in CP, AP/AP-CPn and BP/BP-CPn groups at the time of SCT, respectively. After a median follow-up of 17.3 months from SCT, 14 patients are alive, including 13 in complete molecular response and 1 with an extramedullary relapse. In conclusion, HID-SCT is a potentially curative treatment for T315I + CML patients. For patients in CP/AP, immediate SCT might result in promising survival. The outcome of patients in BP with T315I(+) mutation remains very poor. PMID:26995693

  15. Quantification of CD8+CD38+ T lymphocytes by flow cytometry does not represent a good biomarker to monitor the reactivation of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Vânia Abadia Soares Lino

    2011-01-01

    Full Text Available BACKGROUND: Infection/reactivation of cytomegalovirus is a major cause of morbidity and mortality in immunocompromised transplant patients. It has already been observed in kidney and liver transplantation patients that cytomegalovirus disease is accompanied by significant increases in circulating CD8+CD38+ T lymphocytes. There are no reports that study CD8+CD38+ T lymphocytes to monitor/diagnose cytomegalovirus disease in hematopoietic stem cell transplantation patients. OBJECTIVE: The aim of this study was to evaluate some cellular activation markers on circulating mononuclear cells (CD38 and HLA-DR in patients submitted to hematopoietic stem cell transplantation and to establish any correlation with cytomegalovirus disease as diagnosed by antigenemia. METHODS: Blood samples of 15 transplant patients were analyzed by flow cytometry using anti-CD3, anti-CD4, anti-CD8, anti-CD38, CD16, CD56 and anti-HLA-DR monoclonal antibodies and the results were evaluated in respect to cytomegalovirus antigenemia measured by indirect immunofluorescence. Minitab for Windows was used for statistical analysis and a p-value < 0.05 was considered significant. RESULTS: Patients with positive antigenemia did not show any significant increase in the percentages of cells expressing the CD38 or HLADR activation markers when compared to patients with negative antigenemia. On the contrary, all patients showed high percentages of these cells independent of the presence of cytomegalovirus disease. CONCLUSIONS: This study suggests that the investigation of these lymphocyte sub-populations in patients submitted to hematopoietic stem cell transplantation does not seem to contribute to the early identification of cytomegalovirus disease.

  16. Outcome of poor response Paediatric AML using early SCT

    DEFF Research Database (Denmark)

    Wareham, Neval E; Heilmann, Carsten; Abrahamsson, Jonas;

    2013-01-01

    treated with SCT. MATERIAL AND METHODS: Treatment was given according to the NOPHO-AML 2004 protocol. All patients received AIET (Cytarabine, Idarubicin, Etoposide, Thioguanine) and AM (Cytarabine, Mitoxantrone) as induction. We included poor response defined as > 15% blasts on day 15 after AIET (n = 17......) or > 5% blasts after AM (n = 14, refractory disease). Poor response patients received intensively timed induction and proceeded to SCT when a donor was available. RESULTS: Thirty-one of 267 evaluable patients (12%) had a poor response. SCT was performed in 25; using matched unrelated donors in 13...

  17. Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects

    OpenAIRE

    Jansson, Johan; Hsu, Yu-Chiao; Kuzin, Igor I.; Campbell, Andrew; Mullen, Craig A.

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation is often performed for patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are generally weak and the mechanisms of this weakness are unknown. These studies tested the hypothesis that ALL cells that have survived conventional chemotherapy in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice were injected with mur...

  18. Análise retrospectiva dos pacientes infectados por RSV na unidade de transplante de medula óssea RSV infection after allogeneic hematopoietic stem cell transplantation (HSCT: analysis of 59 patients transplanted in a single institution

    Directory of Open Access Journals (Sweden)

    Flavia Z. Piazera

    2009-01-01

    Full Text Available O vírus sincicial respiratório (RSV é considerado uma causa importante de morbi-mortalidade em pacientes submetidos ao transplante de células-tronco hematopoéticas (TCTH. Mesmo com o uso da ribavirina inalatória (RI, as taxas de mortalidade são de 30% a 40% . O objetivo deste trabalho foi analisar o perfil dos pacientes infectados pelo RSV e a eficácia do tratamento com RI. Realizou-se uma análise retrospectiva de 59 pacientes submetidos ao TCTH com infecção confirmada pelo RSV (métodos de IFI ou PCR entre 02/1991 e 02/2008. A RI foi administrada por 12 horas, na dose de 5 g diluída 200 ml de água destilada, por cinco dias. Quinze pacientes apresentaram infecções (TRI do trato respiratório inferior e 44 pacientes apresentaram infecções (TRS de vias aéreas superiores. No grupo tratado (n=50, quarenta apresentaram infecções no TRS versus dez TRI; no grupo não tratado, quatro TRS versus cinco TRI. Foram constatados vinte óbitos (33,8%, sendo que 13 desses pacientes (65% dos óbitos tiveram suas mortes relacionadas ao RSV. Dentre estes, nove pacientes foram a óbito antes da instituição da RI como terapia padrão. A sobrevida global (SG de todos os pacientes foi de 8,3 meses, sendo 66% para o grupo que utilizou RI versus 11,1% no grupo não tratado(p=0,001. No entanto, a SG foi inferior nos pacientes que apresentaram infecções no TRI (37,5% quando comparadas às infecções do TRS (65,1%, p=0,007. No modelo de regressão de Cox, a única variável independente encontrada foi o tratamento com RI (p=0,001.Respiratory syncytial virus (RSV causes significant mortality in patients submitted to SCT. Despite the use of ribavirin aerosols (RA, mortality rates are still between 30 and 40% in many centers. The objective of this study was to analyze the clinical course and outcome of 59 patients who developed RSV infections after SCT in a single institution. In this retrospective analysis, the diagnosis of RSV infection was

  19. 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.

  20. Impact of Pretransplantation (18)F-Fluorodeoxyglucose-Positron Emission Tomography on Survival Outcomes after T Cell-Depleted Allogeneic Transplantation for Hodgkin Lymphoma.

    Science.gov (United States)

    Reyal, Yasmin; Kayani, Irfan; Bloor, Adrian J C; Fox, Christopher P; Chakraverty, Ronjon; Sjursen, Ann-Marie; Fielding, Adele K; Ben Taylor, Marcus; Bishton, Mark J; Morris, Emma C; Thomson, Kirsty J; Russell, Nigel; Mackinnon, Stephen; Peggs, Karl S

    2016-07-01

    Pretransplant (18)F-fluorodeoxyglucose (FDG) positron emission tomography status is an important prognostic factor for outcomes after autologous stem cell transplantation (SCT) in Hodgkin lymphoma (HL), but its impact on outcomes after allogeneic SCT remains unclear. We retrospectively evaluated outcomes after T cell-depleted allogeneic SCT of 116 patients with nonprogressive HL according to pretransplant Deauville scores. Endpoints were overall survival (OS), progression-free survival (PFS), relapse rate (RR), and nonrelapse-related mortality (NRM). OS, PFS, and RR did not differ significantly between the Deauville 1 to 2 and Deauville 3 to 5 cohorts (OS: 77.5% versus 67.3%, P = .49; PFS: 59.4% versus 55.7%, P = .43; RR: 20.9% versus 22.6%, P = .28 at 4 years). Differences in PFS remained statistically nonsignificant when comparisons were made between Deauville 1 to 3 and Deauville 4 to 5 cohorts (60.9% versus 51.4%, P = .10), and RR remained very similar (21.5% versus 23.8%, P = .42). Multivariate analyses demonstrated trends toward significance for an effect of Deauville score on PFS (hazard ratio 1.82 for Deauville 4 to 5, P = .06) and for number of lines of prior therapy on OS (hazard ratio 2.34 for >5 lines, P = .10). The latter effect appeared to be driven by higher NRM rather than increased RR. Our findings suggest that Deauville score before allogeneic SCT in patients with nonprogressive HL has a relatively modest impact on survival outcomes in comparison with the impact in autologous SCT and that predictive values for the individual patient remain low, indicating that residual FDG-avid disease should not preclude allogeneic SCT. Furthermore, our findings bring into question the importance of attainment of metabolic complete response in this setting if it is at the expense of increasing NRM risk. PMID:27095691

  1. First SCT Barrel arrives at CERN

    CERN Multimedia

    Apsimon, R

    Mid-January saw the arrival at CERN of Barrel #3, the first of four SCT barrels. The barrels are formed as low-mass cylinders of carbon fibre skins on a honeycomb carbon core. They are manufactured in industry and then have all the final precision supports added and the final geometric metrology carried out at Geneva University. Barrel #3, complete with its 384 silicon detector modules, arrived by road from Oxford University in England where the modules were mounted using a purpose-built robot. The modules had been selected from the output of all four barrel module building clusters (in Japan, Scandinavia, USA and the UK). Since Barrel #3 will be exposed to high radiation levels within the tracker volume, these modules, representing over half a million readout channels, have been extensively tested at their operational temperature of around -25 degrees Celcius and at voltages of up to 500V. The dangers of shipping such a fragile component of ATLAS were apparent to all and considerable attention was focused...

  2. ATLAS SCT - Progress on the Silicon Modules

    CERN Multimedia

    Tyndel, M.

    The ATLAS SCT consists of 4088 silicon modules. Each module is made up of 4 silicon sensors with 1536 readout strips. Individual strips are connected to FE amplifiers, discriminators and pipelines on the module, i.e. there are 12 radiation hard ASICs, each containing 128 channels on the module. The sensors and the ASICs were developed for the ATLAS experiment and production is proceeding smoothly with over half the components delivered. The components of a module - 4 silicon sensors, a Cu/polyimide hybrid and pitch adaptor, and 12 ASICs - need to be carefully and precisely assembled onto a carbon and ceramic framework, which supports the module and removes the heat. Eleven production clusters are preparing to carry this out over the next two years. An important milestone for the barrel modules has been passed with the first cluster (KEK) now in production (~40 modules produced). A second cluster UK-B has qualified by producing five modules within specification (see below) and is about to start production. T...

  3. 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

    characteristics, transplantation factors, pulmonary function and self-reported sports activity. In this cross-sectional, population-based study, we measured VO2peak, spirometry and diffusion capacity of the lung (DLCO) 3-10 years post HSCT. Z-scores were calculated by reference values from healthy subjects. Self...

  4. Monitoring and characterization of T-lymphocyte reconstitution after allogeneic stem cell transplantation

    OpenAIRE

    Abu-Khader, Ahmad

    2006-01-01

    After administration of the hematopoietic stem cells inoculum into the eligible patients in the allogeneic setting, many hematopoietic cells reconstitute in the following months to years after transplantation. The reconstituted cells can be pathogen-specific (e.g. cytomegalovirus (CMV)-reactive T cells), leukemia-specific (i.e. graft versus leukemia (GvL) effect) or recipient-specific (e.g. graft-versus-host disease (GvHD)). Thus, valid in vitro immune monitoring strategies should broaden the...

  5. The Hatfield SCT lunar atlas photographic atlas for Meade, Celestron, and other SCT telescopes

    CERN Document Server

    2014-01-01

    In a major publishing event for lunar observers, the justly famous Hatfield atlas is updated in even more usable form. This version of Hatfield’s classic atlas solves the problem of mirror images, making identification of left-right reversed imaged lunar features both quick and easy. SCT and Maksutov telescopes – which of course include the best-selling models from Meade and Celestron – reverse the visual image left to right. Thus it is extremely difficult to identify lunar features at the eyepiece of one of the instruments using a conventional Moon atlas, as the human brain does not cope well when trying to compare the real thing with a map that is a mirror image of it. Now this issue has at last been solved.   In this atlas the Moon’s surface is shown at various sun angles, and inset keys show the effects of optical librations. Smaller non-mirrored reference images are also included to make it simple to compare the mirrored SCT plates and maps with those that appear in other atlases. This edition s...

  6. Research Progress of Impact of Pretransplant Iron Overload on Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Hematologic Neoplasms%移植前铁过载对血液肿瘤患者异基因造血干细胞移植预后影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    张潇予; 黄勇

    2014-01-01

    In recent years,a large number of documents have reported that pretransplant iron overload could increase the non-relapsed-related mortality and reduce the overall survival (OS) rate after allogeneic hematopoietic stem cell transplantation (allo-HSCT),especially increased the risk of infection and organ damage and may lead to acute or chronic graft-versus-host disease (GVHD).The main mechanism is related to excessive iron deposition in tissues and activation of oxygen free radicals which could induce apoptosis,tissue disorders and organ dysfunction.Whether pretransplant iron overload can be used to assess the risk factors of allo-HSCT prognosis and whether allo-HSCT patients can benefit from iron chelation therapy still need more researches to prove.%近年来大量文献证明,移植前铁过载可增加异基因造血干细胞移植(allo-HSCT)后患者的非复发相关死亡率,降低移植后总生存(OS)率,尤其增加感染及器官损伤的风险,可能导致急性及慢性移植物抗宿主病(GVHD)的发生.其主要机制涉及过多铁在组织中的沉积,活化氧自由基,进而诱导细胞凋亡及组织和器官功能障碍.移植前铁过载是否可作为评估allo-HSCT预后的危险因素,祛铁治疗是否可使allo-HSCT患者获益,目前仍需进一步研究证实.

  7. Assessment of the ovarian reserve with anti-Müllerian hormone in women who underwent allogeneic hematopoietic stem cell transplantation using reduced-intensity conditioning regimens or myeloablative regimens with ovarian shielding.

    Science.gov (United States)

    Nakano, Hirofumi; Ashizawa, Masahiro; Akahoshi, Yu; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Junya; Yamazaki, Rie; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2016-07-01

    Conditioning regimens that include cyclophosphamide (CY) and total body irradiation (TBI) induce severe gonadal toxicity and permanent infertility in approximately 90 % of female patients who undergo hematopoietic stem cell transplantation (HSCT). However, the use of ovarian shielding or non-myeloablative regimens may preserve ovarian function. To evaluate the ovarian reserve, serum anti-Müllerian hormone (AMH) levels were retrospectively measured in 11 female HSCT recipients aged less than 40 years, including seven with acute leukemia (AL) and four with aplastic anemia (AA), who received a myeloablative conditioning regimen with ovarian shielding or a reduced-intensity conditioning regimen. In most patients, menstruation had stopped and AMH level had decreased to an undetectable level (<0.1 ng/ml) after HSCT. Most patients showed a recovery of regular menstruation, but AMH levels did not increase immediately after the resumption of menstruation. However, in three AL patients and two AA patients who were evaluable for long-term recovery, AMH level increased gradually beyond 1 year after HSCT. In conclusion, recovery of the serum AMH level may be delayed after HSCT, and the AMH level early after HSCT may not accurately reflect ovarian reserve. A prospective study is required to address the usefulness of measuring the AMH level in HSCT recipients. PMID:27084256

  8. Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial.

    Science.gov (United States)

    Morris, Joan; Rudebeck, Mattias; Neudorf, Steven; Moore, Theodore; Duerst, Reggie; Shah, Ami J; Graham, Michael; Aquino, Victor; Morris, Christopher; Olsson, Birgitta

    2016-07-01

    Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen. PMID:26968792

  9. Clofarabine Does Not Negatively Impact the Outcomes of Patients With Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation

    OpenAIRE

    Mathisen, Michael S.; Kantarjian, Hagop; Jabbour, Elias; Garcia-Manero, Guillermo; Ravandi, Farhad; Faderl, Stefan; Borthakur, Gautam; Cortes, Jorge E.; Quintás-Cardama, Alfonso

    2012-01-01

    We evaluated whether clofarabine-containing chemotherapy predisposed patients to hepatic toxicity (particularly venoocclusive disease [VOD]) after allogeneic stem cell transplantation (allo-SCT). In the group who received clofarabine and subsequent transplantation, there were no cases of VOD, and liver toxicity was comparable to a control group who received standard acute myeloid leukemia (AML) chemotherapy. Other transplant-specific outcomes, including overall survival (OS), were also simila...

  10. Allogeneic stem cell transplantation for mantle cell lymphoma--final report from the prospective trials of the East German Study Group Haematology/Oncology (OSHO).

    Science.gov (United States)

    Krüger, William H; Hirt, Carsten; Basara, Nadezda; Sayer, Herbert G; Behre, Gerhard; Fischer, Thomas; Grobe, Norbert; Maschmeyer, Georg; Niederwieser, Dietger; Dölken, Gottfried

    2014-09-01

    This study was conducted in order to evaluate allogeneic stem cell transplantation (alloSCT) as consolidation for patients with mantle cell lymphoma (MCL). Patients with MCL were included into two prospective trials OSHO #060 (refractory/relapsed) and #074 (de novo). Induction was rituximab and chemotherapy. Responding patients proceeded to alloSCT. Minimal residual disease was monitored by quantitative RT-PCR detecting either t(11;14) or clonospecific CDR-III regions. In case of circulating lymphoma cells, immunomodulation (cyclosporine A withdrawal, rituximab, donor lymphocyte infusion) was initiated. Thirty-three of 39 patients underwent alloSCT after myeloablative (n = 7) or toxicity-reduced (n = 26) conditioning. Leukocytes engrafted at day +16 (median, range 0-101) and platelets at day +14 (0-142). Acute graft-versus-host disease stages I-II occurred in 42 % and stages III-IV in 15 %. Five patients have relapsed after SCT. The overall mortality after SCT was 24 % (n = 8). Median follow-up after SCT was 2.8 years (range 0.0-10.9). Five-year progression-free survival was 67 %, and overall survival 73 % after SCT. The results were comparable for primary MCL and refractory/relapsed disease as well as for related vs. unrelated SCT. Younger patients had a significantly better outcome than the elderly. AlloSCT is a feasible and promising consolidation therapy for relapsed and refractory disease and an attractive option for young patients with de novo MCL of high risk. PMID:24782119

  11. CCR1/CCL5 (RANTES) receptor-ligand interactions modulate allogeneic T-cell responses and graft-versus-host disease following stem-cell transplantation

    OpenAIRE

    Choi, Sung W.; Hildebrandt, Gerhard C.; Olkiewicz, Krystyna M.; Hanauer, David A.; Chaudhary, Meghana N.; Silva, Ines A.; Rogers, Clare E.; Deurloo, Daphne T.; Fisher, Jacki M.; Liu, Chen; Adams, David; Chensue, Stephen W.; Cooke, Kenneth R.

    2007-01-01

    Acute graft-versus-host disease (GVHD) and leukemic relapse are serious complications of allogeneic stem-cell transplantation (SCT). Recruitment of activated T cells to host target tissues or sites of leukemic infiltration (graft-versus-leukemia [GVL]) is likely mediated by chemokine receptor–ligand interactions. We examined the contribution of donor cell CCR1 expression to the development of GVHD and GVL using a well-established murine SCT model (B6 → B6D2F1) and CCR1-deficient mice (CCR1−/−...

  12. The ATLAS SCT Optoelectronics and the Associated Electrical Services

    CERN Document Server

    Abdesselam, A; Apsimon, R J; Band, C; Barr, A J; Batchelor, L E; Bates, R; Bell, P; Bernabeu, J; Bizzell, J; Brenner, R; Brodbeck, T; Bruckman de Renstrom, P; Buttar, C; Carter, J R; Charlton, D G; Cheplakov, A P; Chilingarov, A G; Chu, M L; Cindro, V; Demirkõz, B; Dervan, P J; Dolezal, Z; Dowell, John D; Escobar, C; Spencer, E; Ekelöf, T J C; Eckert, S; Eklund, L; Feld, L; Fraser, T J; French, M; French, R; Fuster, J; Gallop, B J; García, C; Goodrick, M J; Greenall, A; Grillo, A A; Grosse-Knetter, J; Hartjes, F; Hessey, N P; Hill, J C; Homer, R J; Hou, L S; Hughes, G; Ikegami, Y; Issever, C; Jakobs, K; Jackson, J N; Jones, M; Jones, R W L; Jones, T J; Joos, D; Jovanovic, P; Kodys, P; Kohriki, T; Kramberger, G; Lee, S C; Lester, C G; Lindsay, S W; Lozano, M; MacWaters, C P; Magrath, C A; Mahout, G; Mandic, I; Margan, E; Mathesonu, J; McMahon, T J; Meinhardt, J; Mesmer, I; Mikuž, M; Morrissey, M; Nichols, A; Nickerson, R B; O'Shea, V; Pagenis, S; Parker, M A; Parzefall, J; Pater, J; Pernegger, H; Phillips, P W; Postranecky, M; Ratoff, P N; Robson, A; Rudge, A; Runge, K; Sedlak, K; Smith, N A; Stapnes, S; Stugu, B; Tadel, M; Teng, P K; Terada, S; Tricoli, A; Turala, M; Tyndel, M; Ujiie, N; Ullán, M; Unno, Y; Viehhauser, G; Vossebeld, Joost Herman; Warren, M R M; Wastie, R L; Webel, M; Weidberg, A R; Wells, P S; White, D J; Wilson, J A

    2006-01-01

    The requirements for the optical links of the ATLAS SCT are described. From the individual detector modules to the first patch panel, the electrical services are integrated with the optical links to aid in mechanical design, construction and integration. The system architecture and critical elements of the system are described. The optical links for the ATLAS SCT have been assembled and mounted onto the carbon fibre support structures. The performance of the system as measured during QA is summarised and compared to the final performance obtained after mounting modules onto the support structures.

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

    Directory of Open Access Journals (Sweden)

    Sebastian Kobold

    2011-01-01

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

  14. Unrelated and alternative donor allogeneic stem cell transplant in patients with relapsed or refractory Hodgkin lymphoma: a systematic review.

    Science.gov (United States)

    Messer, Melanie; Steinzen, Andrea; Vervölgyi, Elke; Lerch, Christian; Richter, Bernd; Dreger, Peter; Herrmann-Frank, Annegret

    2014-02-01

    Abstract Allogeneic stem cell transplant (allo-SCT) is considered a clinical option for patients with Hodgkin lymphoma (HL) who have experienced at least two chemosensitive relapses. The aim of this systematic review was to determine the benefits and harms of allo-SCT with an unrelated donor (UD) versus related donor (RD) allo-SCT for adult patients with HL. Alternative donor sources such as haploidentical donor cells (Haplo) and umbilical cord blood (UCB) were also included. The available evidence was limited. Ten studies were included in this assessment. Four studies provided sufficient data to compare UD with RD allo-SCT. None of these studies was a randomized controlled trial. Additionally, three non-comparative studies, such as registry analyses, which considered patients with UD transplants were included. The risk of bias in the studies was high. Results on overall and progression-free survival (PFS) showed no consistent tendency in favor of a donor type. Results on therapy-associated mortality and acute (grade II-IV) and chronic graft-versus-host disease were also inconsistent. The study comparing UCB with RD transplants and two non-comparative studies with UCB transplants showed similar results. One of the studies comparing additionally Haplo with RD transplants indicated a benefit in PFS for the Haplo transplant group. In summary, our findings do not indicate a substantial outcome disadvantage of UD and alternative donor sources versus RD allo-SCT for adult patients with advanced HL. PMID:23656201

  15. Performance and operation of the semiconductor tracker (SCT)

    CERN Document Server

    Dervan, P; The ATLAS collaboration

    2013-01-01

    After more than 3 years of successful operation at the LHC, we report on the operation and performance of the ATLAS Semi-Conductor Tracker (SCT) functioning in a high luminosity, high radiation environment. The SCT is constructed of 4088 silicon detector modules, for a total of 6.3 million strips. Each module is designed, constructed and tested to operate as a stand-alone unit, mechanically, electrically, optically and thermally. The modules are mounted into two types of structures: one barrel (4 cylinders) and two end-cap systems (9 disks on each end of the barrel). The SCT silicon micro-strip sensors are processed in the planar p-in-n technology. The signals are processed in the front-end ABCD3TA ASICs, which use a binary readout architecture. Data is transferred to the off-detector readout electronics via optical fibres. We find 99.3% of the SCT modules are operational and the hit efficiency exceeds the design specifications. We will report on the operation and performance of the detector, including an ove...

  16. First Combined SCT/TRT Cosmics Seen in SR1

    CERN Multimedia

    M. Jose Costa; H. Pernegger

    A major milestone for the Inner Detector project has been accomplished in early May as cosmic rays going through both the barrel Semiconductor Tracker (SCT) and Transition Radiation Tracker (TRT) have been successfully recorded in the SR1 building on the ATLAS experimental site at CERN. A cosmic-ray track in the combined SCT-TRT barrel As reported also in this issue of the eNews, in February of this year the SCT barrel was inserted into the TRT in the SR1 building. One eighth of the TRT barrel and a quarter of the SCT barrel were then cabled to power supplies and to the data acquisition system in order to verify the good operation of the detector before installation in the ATLAS cavern. After first checks of noise levels in the final detectors, a critical goal was to study its response to cosmic rays using a set of scintillators to give the external trigger, thus undertaking the enormous challenge of integrating the full chain of the detectors, the DAQ, and the reconstruction and monitoring software. A ...

  17. Study on serological blood group conversion rule and clinical blood transfusion in allogeneic hematopoietic stem cell transplantation%异基因造血干细胞移植血型血清学转换规律与临床输血研究

    Institute of Scientific and Technical Information of China (English)

    余忠清; 高志峰; 李慧玉

    2012-01-01

    目的 探讨异基因造血干细胞移植(allo-HSCT)血型血清学和血型物质转换规律,为临床特殊血型鉴定和输血提供理论基础.方法 HSCT后动态观察受者白细胞和红细胞生命周期,红细胞嵌合状态与完全转型后血型抗体生成与残留以及血型物质的转换规律,用盐水介质试管法和微柱凝胶法正、反定型,免疫抑制法检测血型物质.结果 21例受者造血干细胞植活平均时间为18.6 d.8例主侧血型不合红细胞生长为56.6 d,9例次侧血型不合为25.9 d,4例主、次侧血型均不合为67 d(P0.01).%Objective To explore the conversion rule of serological blood group and blood group substance after successful allogeneic hematopoietic stem cell transplantation, and to provide theory for clinical special blood type identification and blood transfusion. Methods The growth cycle of recipient WBC and RBC, RBC chimera, blood group antibody production and remaining in full transition were observed. Conversion rule of blood group substance, contradiction between cells typing and sera typing were detected by saline medium tube method and microcolumn gel method after stem cells transplantation. Results The average time of engraftment in 21 recipients was about 18.6 days, RBC growth cycle in 8 major blood type incompatibility was 56.6days, 25.9 days in 9 minor blood type incompatibility, 67 days in 4 bidirectional blood type incompatibility (P0.01).

  18. Hemorrhagic cystitis after hematopoietic stem cell trans-plantation: much progress and many remaining issues

    Institute of Scientific and Technical Information of China (English)

    Edmund K. Waller

    2007-01-01

    @@ The manuscript by Xu et al1 addresses an important question in the field of allogeneic hematopoietic progenitor cell transplantation (HPCT): how to identify those patients at risk for hemmoraghic cystitis. The authors performed a retrospective analysis of 250 patients undergoing allogeneic HPCT following myeloablative conditioning with busulfan and cyclophosphamide using a standard post-transplant immunoprophylaxis with cyclosporine, short-course methotrexate and mycophenylate.

  19. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    OpenAIRE

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in pro...

  20. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    OpenAIRE

    Israel Henig; Tsila Zuckerman

    2014-01-01

    Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved an...

  1. Alloantigen expression on non-hematopoietic cells reduces graft-versus-leukemia effects in mice

    OpenAIRE

    Asakura, Shoji; Hashimoto, Daigo; Takashima, Shuichiro; Sugiyama, Haruko; Maeda,Yoshinobu; Akashi, Koichi; Tanimoto, Mitsune; Teshima, Takanori

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is used effectively to treat a number of hematological malignancies. Its beneficial effects rely on donor-derived T cell–targeted leukemic cells, the so-called graft-versus-leukemia (GVL) effect. Induction of GVL is usually associated with concomitant development of graft-versus-host disease (GVHD), a major complication of allogeneic HSCT. The T cells that mediate GVL and GVHD are activated by alloantigen presented on host antigen-pres...

  2. Donor parity no longer a barrier for female-to-male hematopoietic stem cell transplantation

    OpenAIRE

    van Halteren, Astrid GS; Miranda P Dierselhuis; Netelenbos, Tanja; Fechter, Mirjam

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely applied treatment for disorders mainly involving the hematopoietic system. The success of this treatment depends on many different patient- and donor-specific factors. Based on higher CD34+ yields and superior clinical outcomes associated with the use of male donors, males are generally seen as the preferred HSCT donor. In addition, female donors are notorious for bearing memory type lymphocytes induced by previous pregnanc...

  3. The ATLAS SCT grounding and shielding concept and implementation

    CERN Document Server

    Bates, RL; Bernabeu, J; Bizzell, J; Bohm, J; Brenner, R; Bruckman de Renstrom, P A; Catinaccio, A; Cindro, V; Ciocio, A; Civera, J V; Chouridou, S; Dervan, P; Dick, B; Dolezal, Z; Eklund, L; Feld, L; Ferrere, D; Gadomski, S; Gonzalez, F; Gornicki, E; Greenhall, A; Grillo, A A; Grosse-Knetter, J; Gruwe, M; Haywood, S; Hessey, N P; Ikegami, Y; Jones, T J; Kaplon, J; Kodys, P; Kohriki, T; Kondo, T; Koperny, S; Lacasta, C; Lozano Bahilo, J; Malecki, P; Martinez-McKinney, F; McMahon, S J; McPherson, A; Mikulec, B; Mikus, M; Moorhead, G F; Morrissey, M C; Nagai, K; Nichols, A; O'Shea, V; Pater, J R; Peeters, S J M; Pernegger, H; Perrin, E; Phillips, P W; Pieron, J P; Roe, S; Sanchez, J; Spencer, E; Stastny, J; Tarrant, J; Terada, S; Tyndel, M; Unno, Y; Wallny, R; Weber, M; Weidberg, A R; Wells, P S; Werneke, P; Wilmut, I

    2012-01-01

    This paper describes the design and implementation of the grounding and shielding system for the ATLAS SemiConductor Tracker (SCT). The mitigation of electromagnetic interference and noise pickup through power lines is the critical design goal as they have the potential to jeopardize the electrical performance. We accomplish this by adhering to the ATLAS grounding rules, by avoiding ground loops and isolating the different subdetectors. Noise sources are identified and design rules to protect the SCT against them are described. A rigorous implementation of the design was crucial to achieve the required performance. This paper highlights the location, connection and assembly of the different components that affect the grounding and shielding system: cables, filters, cooling pipes, shielding enclosure, power supplies and others. Special care is taken with the electrical properties of materials and joints. The monitoring of the grounding system during the installation period is also discussed. Finally, after con...

  4. The ATLAS SCT grounding and shielding concept and implementation

    Czech Academy of Sciences Publication Activity Database

    Bates, R.L.; Bell, P.J.; Bernabeu, J.; Böhm, Jan; Šťastný, Jan

    2012-01-01

    Roč. 7, MAR (2012), 1-31. ISSN 1748-0221 R&D Projects: GA MŠk LA08032 Institutional research plan: CEZ:AV0Z10100502 Keywords : ATLAS * LHC * SCT * Si microstrip and pad detectors * large detector systems for particle and astroparticle physics * detector grounding Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 1.869, year: 2011

  5. The ATLAS SCT grounding and shielding concept and implementation

    International Nuclear Information System (INIS)

    This paper describes the design and implementation of the grounding and shielding system for the ATLAS SemiConductor Tracker (SCT). The mitigation of electromagnetic interference and noise pickup through power lines is the critical design goal as they have the potential to jeopardize the electrical performance. We accomplish this by adhering to the ATLAS grounding rules, by avoiding ground loops and isolating the different subdetectors. Noise sources are identified and design rules to protect the SCT against them are described. A rigorous implementation of the design was crucial to achieve the required performance. This paper highlights the location, connection and assembly of the different components that affect the grounding and shielding system: cables, filters, cooling pipes, shielding enclosure, power supplies and others. Special care is taken with the electrical properties of materials and joints. The monitoring of the grounding system during the installation period is also discussed. Finally, after connecting more than four thousand SCT modules to all of their services, electrical, mechanical and thermal within the wider ATLAS experimental environment, dedicated tests show that noise pickup is minimised.

  6. Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Schmid, Christoph; Labopin, Myriam; Nagler, Arnon; Niederwieser, Dietger; Castagna, Luca; Tabrizi, Reza; Stadler, Michael; Kuball, Jürgen; Cornelissen, Jan; Vorlicek, Jiri; Socié, Gerard; Falda, Michele; Vindeløv, Lars; Ljungman, Per; Jackson, Graham; Kröger, Nicolaus; Rank, Andreas; Polge, Emmanuelle; Rocha, Vanderson; Mohty, Mohamad

    2012-01-01

    Since information on management and outcome of adults with AML relapsing after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning (RIC HSCT) is scarce, a retrospective registry study was performed by the Acute Leukemia Working Party of EBMT. Among 2815 RIC...

  7. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2012-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative ...

  8. Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation

    OpenAIRE

    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Choi, Eun Young; Min, Chang-Ki

    2015-01-01

    Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H-2b) → B6D2F1 (H-2b/d), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic ...

  9. 异基因造血干细胞移植后慢性炎症性脱髓鞘性多发神经病变一例并文献复习%Chronic inflammatory demyelinating polyneuropathy after allogeneic hematopoietic stem cell transplantation: a case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    胡凯; 王继军; 万伟; 克晓燕

    2011-01-01

    目的 提高对异基因造血干细胞移植( allo-HSCT)后并发慢性炎症性脱髓鞘性多发神经病变( CIDP)的认识,探讨其临床特点、诊断及治疗.方法 报道1例慢性粒细胞白血病患者allo-HSCT 后发生CIDP的临床和实验室检查特征及治疗经过.结果 患者在移植后发生急性及慢性移植物抗宿主病(GVHD),在第+105天起出现慢性迁延反复的多发部位神经系统症状,以面瘫、四肢肌力减退、排尿困难为主,经多次腰椎穿刺脑脊液检查以及神经电生理检查,除外其他神经系统疾病后诊断为CIDP.经静脉丙种球蛋白、糖皮质激素、免疫抑制剂治疗及功能锻炼,GVHD及CIDP有所改善,但终因长期免疫抑制继发感染而死亡.结论 allo-HSCT后CIDP是一种罕见的、诊治困难的神经系统并发症,为移植相关的多种因素所致,GVHD及免疫系统紊乱是主要原因,应及时诊断,合理治疗.%Objective To study chronic inflammatory demyelinating polyneuropathy (CIDP) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the clinical manifestation,diagnosis and treatment.Methods The clinical manifestation,laboratory examination,treatment and outcome of a patient with chronic myeloid leukemia after allo-HSCT were studied.Results Acute and chronic graft-versus-host disease(GVHD) were occurred in the patient followed by chronic multiple nervous system symptoms from +105 day including facioplegia,decreased muscle strength and dysuria.According to clinical manifestation,results of cerebrospinal fluid exam and electroneurophysiology exam,CIDP was diagnosed.The clinical condition was improved after treatment with intravenous immunoglobulin,glucocorticoid, immunosuppressive agents and functional exercises,but the patient died of secondary infection finally.Conclusion CIDP after allo-HSCT is a rare complication of nervous system and difficult to diagnose and treat.Numerous transplant-related causes are probably

  10. HLA全相合异基因造血干细胞移植与免疫抑制剂治疗重型再生障碍性贫血的比较%Allogeneic hematopoietic stem cell transplantation versus immunosuppressive therapy as frontline treatment for severe aplastic anaemia

    Institute of Scientific and Technical Information of China (English)

    徐勇; 欧阳建; 陈兵; 杨永公; 许景艳; 周荣富; 张启国; 邵晓雁; 关朝阳

    2011-01-01

    背景:国外有报道显示异基因造血干细胞移植和免疫抑制疗法治疗急性重型再生障碍性贫血的有效率及总生存期相当,但两种疗法治疗后的生活质量及治疗费用方面的差异报道较少.目的:回顾性分析同胞HLA全相合异基因造血干细胞移植与免疫抑制疗法治疗急性重型再生障碍性贫血的疗效.方法:入选2004-07/2010-10在南京鼓楼医院血液科行同胞HLA全相合异基因造血干细胞移植的7例及行免疫抑制疗法的16例急性重型再生障碍性贫血患者,每3个月定期进行随访.结果与结论:异基因造血干细胞移植组在粒细胞和血小板恢复时间,脱离输血时间,治疗后3个月总有效率及治疗后12个月完全缓解率均优于免疫抑制疗法组,但治疗后12个月总有效率差异无显著性意义.异基因造血干细胞移植组与免疫抑制疗法组的总生存率分别为86%与81.3%,两组比较差异无显著性意义.治疗1年后两组患者总体健康状况及功能健康状况均提示良好,两组住院费用差异无显著性意义.%BACKGROUND: Foreign reports have suggested that allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (1ST) for acute severe aplastic anemia (SAA) have similar clinical effectiveness and overall survival period, but there are few reports about post-treatment quality of life and treatment costs of two different therapies. OBJECTIVE: To summarize the outcome and survival of both HLA matched sibling donor HSCT (allo-HSCT)and IST in 23 SAA patients.METHODS: Totally 7 patients with SAA who received allo-HSCT and 16 patients with SAA who received IST were selected from Department of Hematology, Nanjing Drum Tower Hospital from July 2004 to October 2010. Follow-up was performed every 3 months after treatment to observe the patients' survival, quality of life, cost of hospitalization and analyze the effects. RESULTS AND CONCLUSION: The allo-HSCT therapy was

  11. Hematopoietic stem cell donation: psychological perspectives of pediatric sibling donors and their parents.

    Science.gov (United States)

    Hutt, D; Nehari, M; Munitz-Shenkar, D; Alkalay, Y; Toren, A; Bielorai, B

    2015-10-01

    Allogeneic stem cell transplantation (SCT) is widely used for treatment of various life-threatening pediatric diseases. It is an intensive process that psychologically affects the whole family. Pediatric donors represent a very unique, underreported, group. The aim of this study is to investigate the sibling donors' and their parents' perspective on the donation process. The cohort included 36 sibling donors and 50 parents of pediatric patients who underwent allogeneic SCT between 1995 and 2010 and were alive at the time of the study. Mean age at donation was 14.78±8.350 years in donors' group and 8.22±4.639 years in parents' group. Data were collected by anonymous questionnaires. Three psychological dimensions were analyzed: donors' personal perspective; donor-recipient interpersonal relationship and the influence of the donation on the family unit. Results showed that the donors experienced a wide range of complex emotional responses, positive and negative, whereas the parents' responses were mainly positive and less complex. This study presents both the sibling donor's and parents' perspective, giving a more complete picture of the donation process within the family. The effects of this intense experience of SCT has a long-term impact on the whole family, indicating the need for follow-up and psychosocial support. PMID:26146807

  12. 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. PMID:26752141

  13. Pulmonary Rehabilitation for Bronchiolitis Obliterans Syndrome after Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Tran, Jerry; Norder, Emily; Diaz, Phil; Gary S Phillips; Elder, Pat; Devine, Steven M; Wood, Karen L.

    2012-01-01

    Bronchiolitis obliterans syndrome (BOS) is a progressive, insidious lung disease affecting allogeneic hematopoietic stem cell transplant (HSCT) recipients. Unfortunately, there is no standardized approach for treatment of BOS in post HSCT patients. Pulmonary rehabilitation is a standard treatment in emphysema, an irreversible obstructive lung disease secondary to tobacco abuse. The National Emphysema Treatment Trial (NETT) demonstrated improved exercise tolerance, decrease dyspnea, and increa...

  14. Therapeutic effect of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimen of Bu + Cy for leukemia%减低剂量Bu+Cy预处理方案进行异基因造血干细胞移植治疗白血病的效果观察

    Institute of Scientific and Technical Information of China (English)

    陈姝; 李文; 罗云; 周慷; 张颖; 陈林; 邓建川; 娄世锋

    2012-01-01

    Objective To evaluate the clinical value of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity Bu+Cy conditioning regimen in the treatment of patients with leukemia. Methods The reduced intensity Bu+Cy conditioning regimen including busulfan (Bu) 4 mg/(kg·d) , for 3 d; cyclophosphamide (Cy) 50 mg/(kg·d) , for 2 d, antithymocyte globulin (ATG) 2.5 mg/(kg·d) , for 2/4 d, were used in 15 leukemia patients who underwent allo-HSCT in our department from April 2010 to March 2012. There were 2 cases of acute lymphocytic leukemia, 3 cases of acute non-lymphoid leukemia, 9 cases of chronic myeloid leukemia, and 1 case of Crisis phase of CML. Results All patients achieved successful hemopoietic reconstruction. The median time of the neutrophil recovery >0. 5×109/L was 12 (ranging from 10 to 17) d and the platelet recovery >20 ×109/L was 15 (12 to 27) d after transplantation. In 15 patients, short tandem repeat polymerase chain reaction ( STR-PCR) confirmed that the donor cells were fully implanted on day 30. Transplant-related complications were acute graft-versus-host disease (aGVHD) in 6 patients (40% ) (2 patients with aGVHD = grade Ⅰ , 4 patients with aGVHD = grade Ⅱ , and none with aGVHD = grade Ⅲ-Ⅳ) , chronic graft-versus-host disease (cGVHD) in 8 patients (53. 3% ) (2 cases of extensive-type, and 6 cases of limited-type) , hemorrhagic cystitis in 3 patients ( 20% ) , and infected cytomegalovirus in 4 patients (26.7% ). There was no other serious complication. All patients were followed up for a median time of 15.4 months (ranging from 6 to 30). One patient (6. 7% ) died of side effect related to the conditional regimen. Two patients (13. 3%) got recurrence, and the rest (80. 0%) survived event-free for 4 to 30 months. Conclusion After treated with reduced intensity Bu+Cy conditioning regimen-HSCT, leukemia patients have a better hematopoietic reconstitution and less transplant-related complications. It is also suggested

  15. Parental stress and perceived vulnerability at 5 and 10 years after pediatric SCT.

    Science.gov (United States)

    Vrijmoet-Wiersma, C M J; Egeler, R M; Koopman, H M; Bresters, D; Norberg, A L; Grootenhuis, M A

    2010-06-01

    With the aim of assessing parental stress after SCT, 73 parents of children and adolescents who underwent SCT 5 or 10 years ago responded to questionnaires on general distress (General Health Questionnaire (GHQ)), disease-related stress (Pediatric Inventory for Parents-short form (PIP-SF)) and perceptions of child vulnerability (Child Vulnerability Scale (CVS)). General distress scores were comparable with the reference groups, but 40% of the mothers at 5 years after SCT reported increased stress levels as compared with 26% in the community-based reference group. Disease-related stress was comparable with the reference group of parents of children who were just off cancer treatment, 5 years after SCT. At 10 years after SCT, scores were lower than the reference group. Perceived child vulnerability did diminish over time, but remained high in parents of SCT survivors, compared with parents of healthy children: 96% of the parents at 5 years after SCT and 76% of the parents at 10 years after SCT scored above the cutoff point. Perceived vulnerability was found to be a predictor for parental disease-related stress. To conclude, although most parents of SCT survivors are resilient, the majority of parents perceive their child to be much more vulnerable as compared with parents of healthy children. This perception is associated with disease-related stress and may induce overprotective parenting. PMID:19881554

  16. Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry.

    Science.gov (United States)

    Greinix, Hildegard T; Nachbaur, David; Krieger, Otto; Eibl, Margit; Knöbl, Paul; Kalhs, Peter; Lutz, Dieter; Linkesch, Werner; Niederwieser, Dietger; Hinterberger, Wolfgang; Lechner, Klaus; Rosenmayr, Agathe; Gritsch, Beate

    2002-06-01

    Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined. PMID:12060131

  17. Amplitude Modulation in the δ Sct star KIC 7106205

    Directory of Open Access Journals (Sweden)

    Bowman Dominic. M.

    2015-01-01

    Full Text Available The δ Sct star KIC 7106205 showed amplitude modulation in a single p mode, whilst all other p and g modes remained stable in amplitude and phase over 1470 d of the Kepler dataset. The data were divided into 30 time bins of equal length and a series of consecutive Fourier transforms was calculated. A fixed frequency, calculated from a least-squares fit of all data, allowed amplitude and phase for every mode in each time bin to be tracked. The missing p mode energy was not transferred to any other visible modes.

  18. Beam tests of ATLAS SCT silicon strip detector modules

    International Nuclear Information System (INIS)

    The design and technology of the silicon strip detector modules for the Semiconductor Tracker (SCT) of the ATLAS experiment have been finalised in the last several years. Integral to this process has been the measurement and verification of the tracking performance of the different module types in test beams at the CERN SPS and the KEK PS. Tests have been performed to explore the module performance under various operating conditions including detector bias voltage, magnetic field, incidence angle, and state of irradiation up to 3x1014 protons per square centimetre. A particular emphasis has been the understanding of the operational consequences of the binary readout scheme

  19. A Randomized Trial of One vs. Two Doses of Influenza Vaccine Following Allogeneic Transplantation

    OpenAIRE

    Karras, Nicole A.; Weeres, Matthew; Sessions, Wendy; Xu, Xiyan; DeFor, Todd; Young, Jo-Anne H.; Stefanski, Heather; Brunstein, Claudio; Cooley, Sarah; Miller, Jeffrey S.; Blazar, Bruce R.; Wagner, John E.; Verneris, Michael R.

    2012-01-01

    Influenza infection following allogeneic hematopoietic cell transplantation (allo-HCT) can result in severe complications. The effectiveness of the annual vaccine depends on age, immune competence and the antigenic potential of the 3 strains included (1). . We hypothesized that a second vaccine dose, the standard of care for vaccine-naïve children, might improve post-HCT immune responses. Patients >60 days post-HCT were randomized to receive either 1 (n=33) or 2 (n=32) influenza vaccine doses...

  20. Epstein-Barr virus-associated leukemic lymphoma after allogeneic stem cell transplantation.

    Science.gov (United States)

    Takamatsu, Hiroyuki; Araki, Raita; Nishimura, Ryosei; Yachie, Akihiro; Espinoza, J Luis; Okumura, Hirokazu; Yoshida, Takashi; Kuzushima, Kiyotaka; Nakao, Shinji

    2016-07-01

    Leukemic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative diseases (PTLD) following allogeneic hematopoietic stem cell transplantation are extremely rare. We can successfully treat an EBV-associated leukemic lymphoma patient with rituximab, cidofovir, and donor lymphocyte infusion (DLI). In the present case, EBV-specific T cells that were present in the peripheral blood before rituximab administration treatment rapidly increased after DLI in association with a decrease in the EBV-DNA load. PMID:27218416

  1. Role of allogeneic stem cell transplantation in mantle cell lymphoma.

    Science.gov (United States)

    Cohen, Jonathon B; Burns, Linda J; Bachanova, Veronika

    2015-04-01

    Despite a wide spectrum of treatment options, mantle cell lymphoma (MCL) remains a challenging hematologic malignancy to manage. Advances in front-line therapy, including the monoclonal antibody rituximab and increasing use of cytarabine, have improved remission rates. Autologous hematopoietic cell transplantation (HCT) can effectively consolidate remission of MCL, leading to encouraging survival beyond 5 yr. However, nearly all patients with MCL will relapse and require salvage therapy. Novel agents such as ibrutinib, bortezomib, and lenalidomide have dramatically expanded the options for treating relapsed MCL. In this review, we summarize the clinical evidence supporting the use of allogeneic donor HCT in MCL and make recommendations on indications for its use. Data suggest that allogeneic donor HCT is the only curative therapy for patients with poor prognosis or aggressive MCL. Patient selection, timing, and optimal use remain a matter of scientific debate and given the rapidly changing therapeutic landscape of MCL, the outcomes of allogeneic HCT should be interpreted in the context of novel therapeutics. PMID:25154430

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

    Directory of Open Access Journals (Sweden)

    Thielen Alexander

    2010-03-01

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

  3. A COMPARISON OF HLA-IDENTICAL SIBLING ALLOGENEIC VERSUS AUTOLOGOUS TRANSPLANTATION FOR DIFFUSE LARGE B-CELL LYMPHOMA: A REPORT FROM THE CIBMTR

    Science.gov (United States)

    Lazarus, Hillard M.; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M.; Ataergin, Asli Selmin; Bitran, Jacob D.; Bolwell, Brian J.; Freytes, César O.; Gale, Robert Peter; Goldstein, Steven C.; Hale, Gregory A.; Inwards, David J.; Klumpp, Thomas R.; Marks, David I.; Maziarz, Richard T.; McCarthy, Philip L.; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C.; Schouten, Harry C.; Slavin, Shimon; Winter, Jane N.; van Besien, Koen; Vose, Julie M.; Hari, Parameswaran N.

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients age ≥ 18 years undergoing first autologous (n=837) or myeloablative allogeneic hematopoietic cell transplant (HCT) (n=79) between 1995–2003 reported to the CIBMTR. Median follow-up was 81 months for allogeneic HCT vs. 60 months for autologous. Allogeneic HCT recipients were more likely to have high risk disease features including higher stage, more prior chemotherapy regimens and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (RR 4.88, 95% CI, 3.21–7.40, p50 years), lower performance score, chemoresistance and earlier year of transplant. In a cohort of mainly high risk DLBCL patients, upfront myeloablative allogeneic HCT while associated with increased early mortality was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  4. The Role of Pattern-Recognition Receptors in Graft-Versus-Host Disease and Graft-Versus-Leukemia after Allogeneic Stem Cell Transplantation

    OpenAIRE

    Heidegger, Simon; van den Brink, Marcel R. M.; Haas, Tobias; Poeck, Hendrik

    2014-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential for certain aggressive hematopoietic malignancies. Its success is limited by acute graft-versus-host disease (GVHD), a life-threatening complication that occurs when allo-reactive donor T cells attack recipient organs. There is growing evidence that microbes and innate pattern-recognition receptors (PRRs) such as toll-like receptors (TLR) and nod-like receptors (NLR) are critically inv...

  5. Allogeneic hematopoietic stem cell transplantation in patients with polycythemia vera or essential thrombocythemia transformed to myelofibrosis or acute myeloid leukemia: a report from the MPN Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

    NARCIS (Netherlands)

    Lussana, F.; Rambaldi, A.; Finazzi, M.C.; Biezen, A. van; Scholten, M.; Oldani, E.; Carobbio, A.; Iacobelli, S.; Finke, J.; Nagler, A.; Volin, L.; Lamy, T.; Arnold, R.; Mohty, M.; Michallet, M.; Witte, T.J.M. de; Olavarria, E.; Kroger, N.

    2014-01-01

    The clinical course of polycythemia vera and essential thrombocythemia is potentially associated with long-term severe complications, such as evolution to myelofibrosis or acute myeloid leukemia. Allogeneic stem cell transplantation is currently the only potentially curative treatment for advanced p

  6. Outcome of lower-intensity allogeneic transplantation in non-Hodgkin lymphoma after autologous transplantation failure.

    Science.gov (United States)

    Freytes, César O; Zhang, Mei-Jie; Carreras, Jeanette; Burns, Linda J; Gale, Robert Peter; Isola, Luis; Perales, Miguel-Angel; Seftel, Matthew; Vose, Julie M; Miller, Alan M; Gibson, John; Gross, Thomas G; Rowlings, Philip A; Inwards, David J; Pavlovsky, Santiago; Martino, Rodrigo; Marks, David I; Hale, Gregory A; Smith, Sonali M; Schouten, Harry C; Slavin, Simon; Klumpp, Thomas R; Lazarus, Hillard M; van Besien, Koen; Hari, Parameswaran N

    2012-08-01

    We studied the outcome of allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning regimens (reduced-intensity conditioning and nonmyeloablative) in patients with non-Hodgkin lymphoma who relapsed after autologous hematopoietic stem cell transplantation. Nonrelapse mortality, lymphoma progression/relapse, progression-free survival (PFS), and overall survival were analyzed in 263 patients with non-Hodgkin lymphoma. All 263 patients had relapsed after a previous autologous hematopoietic stem cell transplantation and then had undergone allogeneic hematopoietic stem cell transplantation from a related (n = 26) or unrelated (n = 237) donor after reduced-intensity conditioning (n = 128) or nonmyeloablative (n = 135) and were reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2006. The median follow-up of survivors was 68 months (range, 3-111 months). Three-year nonrelapse mortality was 44% (95% confidence interval [CI], 37%-50%). Lymphoma progression/relapse at 3 years was 35% (95% CI, 29%-41%). Three-year probabilities of PFS and overall survival were 21% (95% CI, 16%-27%) and 32% (95% CI, 27%-38%), respectively. Superior Karnofsky Performance Score, longer interval between transplantations, total body irradiation-based conditioning regimen, and lymphoma remission at transplantation were correlated with improved PFS. Allogeneic hematopoietic stem cell transplantation after lower-intensity conditioning is associated with significant nonrelapse mortality but can result in long-term PFS. We describe a quantitative risk model based on pretransplantation risk factors to identify those patients likely to benefit from this approach. PMID:22198543

  7. Parental stress and perceived vulnerability at 5 and 10 years after pediatric SCT

    NARCIS (Netherlands)

    C.M.J. Vrijmoet-Wiersma; R.M. Egeler; H.M. Koopman; D. Bresters; A.L. Norberg; M.A. Grootenhuis

    2010-01-01

    With the aim of assessing parental stress after SCT, 73 parents of children and adolescents who underwent SCT 5 or 10 years ago responded to questionnaires on general distress (General Health Questionnaire (GHQ)), disease-related stress (Pediatric Inventory for Parents-short form (PIP-SF)) and perce

  8. Design and development of a work robot to place ATLAS SCT modules onto barrel cylinders

    CERN Document Server

    Terada, S; Honma, F; Ikegami, Y; Iwata, Y; Kato, Y; Kobayashi, H; Kohriki, T; Kondo, T; Nakano, I; Sengoku, H; Takashima, R; Tanaka, R; Ujiie, N; Unno, Y; Yasuda, S

    2005-01-01

    More than 2000 silicon modules need to be placed and fastened on the ATLAS SCT barrel tracker. A semi-automatic pick-and-place work robot was designed and developed to cope with the module placement for the SCT barrel assembly. We found that this robot could place modules to a mechanical precision of better than 25 mum.

  9. Who is fit for allogeneic transplantation?

    Science.gov (United States)

    Deeg, H Joachim; Sandmaier, Brenda M

    2010-12-01

    The use of allogeneic hematopoietic cell transplantation (HCT) has expanded progressively, facilitated by the increasing availability of unrelated donors and cord blood, and the inclusion of older patients as transplantation candidates. Indications remain diagnosis-dependent. As novel nontransplantation modalities have been developed concurrently, many patients come to HCT only when no longer responding to such therapy. However, patients with refractory or advanced disease frequently relapse after HCT, even with high-dose conditioning, and more so with reduced-intensity regimens as used for patients of older age or with comorbid conditions. Thus, patients with high-risk malignancies who have substantial comorbidities or are of advanced age are at high risk of both relapse and nonrelapse mortality and should probably not be transplanted. Being in remission or at least having shown responsiveness to pre-HCT therapy is generally associated with increased transplantation success. In addition, to handle the stress associated with HCT, patients need a good social support system and a secure financial net. They must be well informed, not only about the transplantation process, but also about expected or potential post-HCT events, including graft-versus-host disease and delayed effects that may become manifest only years after HCT. PMID:20702782

  10. Hematopoietic stem cells and progenitors of chronic myeloid leukemia express leukemia-associated antigens: implications for the graft-versus-leukemia effect and peptide vaccine-based immunotherapy

    OpenAIRE

    Yong, Agnes S.M.; Keyvanfar, Keyvan; Eniafe, Rhoda; Savani, Bipin N.; Rezvani, Katayoun; Sloand, Elaine M.; Goldman, John M.; Barrett, A. John

    2008-01-01

    The cure of chronic myeloid leukemia (CML) patients following allogeneic stem cell transplantation (SCT) is attributed to graft-versus-leukemia (GVL) effects targeting alloantigens and/or leukemia-associated antigens (LAA) on leukemia cells. To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA...

  11. Allogeneic hematopoietic stem cell transplantation following reduced intensity conditioning regimen as salvage therapy for refractory leukemia%减低强度预处理的异基因造血干细胞移植拯救性治疗难治性白血病

    Institute of Scientific and Technical Information of China (English)

    姜杰玲; 王椿

    2009-01-01

    Several hot questions such as selection of patients and favorable time of transplantation, design of conditioning regimen, monitoring of chimerism and complication of graft versus host disease (GVHD) in allogeneic hematopoietic stem cell transplantation following reduced intensity regimen (RIC-HSCT) as salvage therapy for refractory leukemia are discussed in this article. More and more investigators began to recognize that it was not a fundamental to undergo transplantation in complete remission for patients with refractory leukemia, since it may expend patients' physical status. RIC-HSCT may be substantially considered as a kind of adoptive immunotherapy, so that immunologic attacking targets and the latency of immunoreactian must be considered when making the decision to use, lacking of attacking targets and rapidly growing diseases seemed to be less susceptible to control. Commonly used reduced intensity regimens differed significantly, but it was clear that dose intensity was very important in refractory leukemia. In fact, many investigators used intermediate dosage between criteria of "non-myeloablative" and conventional myeloablative regimens. Complete donor chimerism is the hallmark of engraftment but often delayed in RIC-HSCT. Since sustained complete donor chimerism induced persistent graft-versus-leukemia (GVL) effect play an important role in patients' long-term survival, it was recommended that sensitive techniques (eg. STR-PCR) should be used to analysis chimerism and should be measured more frequently (every 2-4 weeks), and lineage-specific chimerism (eg. T cell) analysis was also recommended. As compared with traditional HSCT, the incidences of acute and chronic GVHD are similar and the onset of GVHD is associated with the GVL effect. Decrease or interruption of immunosuppressive drugs early after transplantation and donor lymphocyte infusion may facilitate transformation to complete donor chimerism, so that it may benefit patients with advanced

  12. 减量伏立康唑一级预防异基因造血干细胞移植后侵袭性真菌病的临床研究%Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    邱志祥; 任汉云; 岑溪南; 欧晋平; 许蔚林; 王茫桔; 王莉红; 董玉君; 李渊

    2014-01-01

    目的 探讨静脉应用伏立康唑对异基因造血干细胞移植(allo-HSCT)后侵袭性真菌病(IFD)一级预防的疗效及耐受性.方法 移植前无真菌感染的allo-HSCT患者从预处理开始应用伏立康唑注射液,直至患者的中性粒细胞恢复至0.5× 109/L以上,以口服氟康唑者为对照组,分析两组间IFD易感因素有无差异,比较两组IFD发生率及药物不良反应的差异.结果 227例患者在移植后3个月内有33例(14.54%)发生IFD,中位随访38(5~76)个月,发生IFD患者累计死亡13例(33.96%),20例存活,总生存率60.61%;194例未发生IFD患者,累计死亡40例(19.89%),154例(79.38%)存活,两组间总生存率差异有统计学意义(P=0.029).227例患者中,83例应用伏立康唑行一级预防,发生IFD者7例(8.43%),对照组144例患者发生IFD 26例(18.06%),两组IFD发生率差异有统计学意义(P=0.048).对两组间的性别、年龄、既往有无慢性病、移植时是否为进展期血液病、移植方式、预处理方案、粒细胞缺乏时间、有无急性移植物抗宿主病、有无CMV感染等因素逐一进行比较,结果显示两组上述因素差异无统计学意义(P>0.05).伏立康唑和氟康唑两组间转氨酶升高患者比例差异无统计学意义(P>0.05).应用伏立康唑出现幻听或视觉障碍等不良反应的比例不高.结论 应用静脉伏立康唑对allo-HSCT患者行IFD的一级预防的效果明显优于氟康唑,且患者对治疗的耐受性良好.%Objective To investigate the efficacy and tolerability of intravenous vonconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods At the time of conditioning regimen,patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5 × 109/L.Patients treated with oral fluconazole,200 mg per day,were control group

  13. 异基因造血干细胞移植后早期特发性肺炎综合征的危险因素及发病机制%Clinical study of idiopathic pneumonia syndrome early after allogeneic hematopoietic stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    胡峻岩; 朱康儿; 张涛; 钟隽; 陈洁

    2009-01-01

    目的 研究异基凶造血干细胞移植(allo-HSCT)术后早期特发性肺炎综合征(IPS)的独立危险因素及发病机制.方法 同顾件分析192例allo-HSCT受者的临床资料,观察术后急性移植物抗宿主病(aGVHD)和IPS的发牛情况及其临床表现,对患者年龄、性别、原发病、移植时疾病状态(高危组70例,疾病处于难治、未缓解状态;标危组122例,疾病处于缓解状态)、供者类型、HLA相合程度、移植类型、预处理方案、急性移植物抗宿主病(aGVHD)、aGVHD程度、aGVHD累及器官等11项临床因素进行单因素分析,将有统计学意义的因素进行Logistic多因素同归分析,筛选出发生IPS的独立危险因素,并结合文献,探讨其发病机制.结果 192例allo-HSCT受者中,有23例发生IPS,发生时间为术后76 d(32~120 d),其中20例经治疗无效死亡,发病至死亡的时间为9 d(3~92 d),其余3例治愈.23例IPS患者中,有19例发生过aGVHD,其中肠道aGVHD16例.单因素分析显示,高危组、非亲缘供者、HLA不合、发生aGVHD、Ⅲ~Ⅳ度aGVHD及肠道aGVHD等6个因素具有统计学意义;多凶素分析显示,非亲缘供者、Ⅲ~Ⅳ度aGVHD和肠道aGVHD等3个因素是发生IPS的独立危险因素.结论 非亲缘供者、Ⅲ~Ⅳ度aGVHD及肠道aGVHD是发生IPS的独立危险因素;IPS可能是由aGVHD引起的肺部病变.%Objective To investigate the independent risk factors and the pathogenesis of idiopathic pneumonia syndrome (IPS) early following allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods We retrospectively reviewed the clinical data of 192 patients undergoing allo-HSCT and analyzed the incidence and clinical manifestations of 23 cases of IPS.The 11 clinical parameters were selected for Logistic univariate analysis: age, gender, underlying disease, disease status at transplant, transplant type, conditioning regimens, donor type, aGVHD, severity of aGVHD, HLA disparity, organ involvement

  14. Expression and significance of CD4+ CD25+ Foxp3+ T cells in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation%骨髓或外周血中CD4+CD25+Foxp3+调节性T淋巴细胞与aGVHD的关系

    Institute of Scientific and Technical Information of China (English)

    王晓娟; 车传珍; 周昱男; 刘仲萍; 黄士昂

    2009-01-01

    目的 研究患者异基因造血干细胞移植(allo-HSCT)前后骨髓或外周血单个核细胞中CD4+CD25+Foxp3+调节性T淋巴细胞(以下简称CD4+CD25+Foxp3+T细胞)的比率、Foxp3 mRNA和Foxp3蛋白的表达与急性移植物抗宿主病(aGVHD)的关系.方法 选择37例行HIA相合异基因造血干细胞移植(allo-HSCT))的患者作为研究对象.采用流式细胞术检测患者allo-HSCT前7天(-7 d)、移植当天(0 d)、移植后30天(+30d)、+60 d和+90 d时骨髓或外周血单个核细胞中CD4+CD25+Foxp3+T细胞所占的比率;定量聚合酶链反应(PCR)检测Foxp3 mRNA相对表达量;蛋白印迹(Western blot)法检测Foxp3的蛋白表达水平.结果 37例患者存移植后100 d内发生aGVHD 13例(aGVHD组),未发生aGVHD 24例(无aGVHD组).CD4+CD25+Foxp3+T细胞的比率在0 d时最低,与-7、+30、+60、+90d时比较.差异均有统计学意义(P<0.01);与aGVHD组比较,无aGVHD组患者的CD4+CD25+Foxp3+T细胞的比率明显升高,差异有统计学意义(P<0.01).aGVHD组患者移植后Foxp3的表达水平逐渐升高,但明显低于无aGVHD组,尤其在+60和+90 d时的差异有统计学意义(P<0.01).Western blot法检测结果 表明,aGVHD组受者的Foxp3蛋白表达也明显低于无aGVHD组.结论 CD4+CD25+Foxp3+T细胞对防止发生aGVHD具有重要作用,监测患者骨髓或外周血中CD4+CD25+Foxp3+T细胞的比率可以预测aGVHD的发生.%Objective To investigate the expression and significance of CD4+ CD25+ Foxp3+ T Cells, Foxp3 mRNA and Foxp3 protein in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Thirty-seven donor grafts and their respective clinical characteristics were evaluated. Flow cytometric analysis was performed to assess the percentage of CD4+ CD25+ Foxp3+ T cells in the recipients before, and 0, 30, 60, and 90 days after allo-HSCT. The relative expression of Foxp3 mRNA was detected by real time reverse transcription-polymerase chain

  15. Chemotherapy supported by allogeneic hematopoietic stem cell transfusion for treatment of elderly non-Hodgkins lymphoma:a report of 3 cases%异基因造血干细胞输注支持下化疗治疗老年淋巴瘤3例报告

    Institute of Scientific and Technical Information of China (English)

    王丽; 李云双; 陈永升; 聂伟业; 尹晓林

    2015-01-01

    Objective To investigate the clinic efficacy of combined chemotherapy supported by allogeneic hematopoietic stem cell transfusion(microtransplantation) for elderly patients with non-Hodgkins lymphoma(NHL).Methods Three elderly patients with NHL aged from 70 to 78 years were enrolled in the study .The patient in Case 1 relapsed after multiple chemotherapy .The patents in Case 2 and Case 3 were newly diagnosed as NHL ,and were treated with chemotherapy regimen of CHOP ( cyclophosphamide +doxorubicin+vincristine+prednisone ) or GeMod( gemcitabine+oxaliplatin+dexamethasone ) .The donors were children of patients with human leukocyte antigen semi-matched.Peripheral blood stem cells ( PBSC) from the donors were mobilized with granulocyte colony-stimulating factor and then were collected.Patients were transfused with PBSC 36 hours after the chemotherapy finished .The disease status,survival time,myelosuppression and side effects were observed .Results The disease statuses after treatment of Case 1,Case 2 and Case 3 were stable disease,complete response and partial response ,respectively.The survival time of Case 1,Case 2 and Case 3 was 4 months,26 months and 10 months, respectively .Granulocytopenia was observed in Case 1 during the third and forth period of chemotherapy ,and severe thrombocytopenia only occurred in Case 1 during the forth period.Severe myelosuppression did not occurred in other cases .None of three cases received transfusion of platelet .Graft versus host disease was not found in any patients .Conclusion Chemotherapy combined with microtransplantation has mild myelosuppression ,and was safe for elderly patients with NHL .Large-scale clinic study for further research is deserved .%目的:观察异基因造血干细胞分次输注(微移植)支持下联合化疗治疗老年非霍奇金淋巴瘤( NHL )的临床疗效。方法 NHL老年患者3例,年龄70~78岁,其中病例1为反复治疗后复发患者,病例2和病例3均为初治患者

  16. Metagenomic Analysis of the Stool Microbiome in Patients Receiving Allogeneic Stem Cell Transplantation: Loss of Diversity Is Associated with Use of Systemic Antibiotics and More Pronounced in Gastrointestinal Graft-versus-Host Disease

    Science.gov (United States)

    Holler, Ernst; Butzhammer, Peter; Schmid, Karin; Hundsrucker, Christian; Koestler, Josef; Peter, Katrin; Zhu, Wentao; Sporrer, Daniela; Hehlgans, Thomas; Kreutz, Marina; Holler, Barbara; Wolff, Daniel; Edinger, Matthias; Andreesen, Reinhard; Levine, John E.; Ferrara, James L.; Gessner, Andre; Spang, Rainer; Oefner, Peter J.

    2016-01-01

    Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. PMID:24492144

  17. Recent results from the ATLAS SCT irradiation programme

    CERN Document Server

    Buttar, C M; Carter, J R; Casse, G L; Costa, M; Dawson, I; Drage, L M; Greenall, A; Grigson, C; Harper, R S; Hill, J C; Johansen, L G; Moorhead, G F; Morgan, D; Nicholson, R; Phillips, P; Riedler, P; Robinson, D; Sánchez, J; Stapnes, Steinar; Stugu, B; Werner, A

    2000-01-01

    The irradiation facility at the CERN proton synchrotron, set up to irradiate full-size prototypes of silicon microstrip detectors for the ATLAS semiconductor tracker, is described and measurements of the detector currents during irradiation are reported. The detector dark currents can be described by bulk radiation damage models demonstrating the radiation hardness of the detector design and allowing the current damage factor alpha and the acceptor introduction term p to be determined. Results from testbeam studies of a module with an irradiated detector and binary readout in a magnetic field and with the beam incident over a range of angles are reported. The hit efficiency and spatial resolution satisfy the requirements for the SCT provided the detector is operated at the full charge collection voltage. The Lorentz angle was not found to be affected by the irradiation. (11 refs).

  18. Hematopoietic Stem Cell Transplantation—50 Years of Evolution and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Israel Henig

    2014-10-01

    Full Text Available Hematopoietic stem cell transplantation is a highly specialized and unique medical procedure. Autologous transplantation allows the administration of high-dose chemotherapy without prolonged bone marrow aplasia. In allogeneic transplantation, donor-derived stem cells provide alloimmunity that enables a graft-versus-tumor effect to eradicate residual disease and prevent relapse. The first allogeneic transplantation was performed by E. Donnall Thomas in 1957. Since then the field has evolved and expanded worldwide. New indications beside acute leukemia and aplastic anemia have been constantly explored and now include congenital disorders of the hematopoietic system, metabolic disorders, and autoimmune disease. The use of matched unrelated donors, umbilical cord blood units, and partially matched related donors has dramatically extended the availability of allogeneic transplantation. Transplant-related mortality has decreased due to improved supportive care, including better strategies to prevent severe infections and with the incorporation of reduced-intensity conditioning protocols that lowered the toxicity and allowed for transplantation in older patients. However, disease relapse and graft-versus-host disease remain the two major causes of mortality with unsatisfactory progress. Intense research aiming to improve adoptive immunotherapy and increase graft-versus-leukemia response while decreasing graft-versus-host response might bring the next breakthrough in allogeneic transplantation. Strategies of graft manipulation, tumor-associated antigen vaccinations, monoclonal antibodies, and adoptive cellular immunotherapy have already proved clinically efficient. In the following years, allogeneic transplantation is likely to become more complex, more individualized, and more efficient.

  19. Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia.

    NARCIS (Netherlands)

    Dickinson, A.M.; Pearce, K.F.; Norden, J.; O'Brien, S.G.; Holler, E.; Bickeboller, H.; Balavarca, Y.; Rocha, V.; Kolb, H.J.; Hromadnikova, I.; Sedlacek, P.; Niederwieser, D.; Brand, R.; Ruutu, T.; Apperley, J.; Szydlo, R.; Goulmy, E.; Siegert, W.; Witte, T.J.M. de; Gratwohl, A.

    2010-01-01

    BACKGROUND: Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. DESIGN AND METHODS: In this study, we assessed the effect of si

  20. Impact of genomic risk factors on outcome after hematopoietic stem cell transplantation for patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Dickinson, Anne M.; Pearce, Kim F.; Norden, Jean; O'Brien, Stephen G.; Holler, Ernst; Bickeboeller, Heike; Balavarca, Yesilda; Rocha, Vanderson; Kolb, Hans-Jochem; Hromadnikova, Ilona; Sedlacek, Petr; Niederwieser, Dietger; Brand, Ronald; Ruutu, Tapatti; Apperleyy, Jane; Szydlo, Richard; Goulmy, Els; Siegert, Wolfgang; de Witte, Theo; Gratwohl, Alois

    2010-01-01

    Background Non-HLA gene polymorphisms have been shown to influence outcome after allogeneic hematopoietic stem cell transplantation. Results were derived from heterogeneous, small populations and their value remains a matter of debate. Design and Methods In this study, we assessed the effect of sing

  1. Human Herpesvirus 6 Infection after Hematopoietic Cell Transplantation: Is Routine Surveillance Necessary?

    OpenAIRE

    Betts, Brian C.; Young, Jo-Anne H.; Ustun, Celalettin; Cao, Qing; Weisdorf, Daniel J.

    2011-01-01

    Human herpesvirus 6 (HHV6) may be an important pathogen following allogeneic hematopoietic cell transplantation (HCT). We prospectively evaluated weekly HHV6 viremia testing after allogeneic HCT using a quantitative polymerase chain reaction (PCR)-based assay. HHV-6 viremia was detected in 46 of 82 (56%) patients at a median of 23 days post-HCT (range: day + 10 to + 168). More males (65% vs females 39%, P = .03) and recipients of umbilical cord blood (UCB 69% vs unrelated donor [URD], 46% vs ...

  2. ALLOGENEIC STEM CELL TRANSPLANTATION IN FIRST COMPLETE REMISSION

    Science.gov (United States)

    Oran, Betul; Weisdorf, Daniel J.

    2016-01-01

    Purpose of review The optimal post-remission therapy of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. This review summarizes the recent developments in the clinical research and therapeutic applications defining the role of allogeneic hematopoietic stem cell transplantation (allo-HCT) in CR1. Recent findings Molecular markers in combinations with cytogenetics have improved the risk stratification and informed decision-making in patients with AML in CR1. In parallel, several important advances in the transplant field, such as better supportive care, improved transplant technology, increased availability of alternative donors, and reduced-intensity conditioning have improved the safety as well as access of allo-HCT for a larger number of patients. Summary The progress in risk stratification and transplant technology dictate that early donor identification search should be initiated for all eligible AML patients in CR1. PMID:21912256

  3. Research on the therapeutic effect of peripheral blood mononuclear cells infusion from donors stimulated with granulocyte colony-stimulating factor in the treatment of patient with relapsed leukemia after allogeneic hematopoietic stem cell transplantation*%G-CSF动员供者外周血单个核细胞输注治疗异基因造血干细胞移植后复发白血病的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘嘉; 高力; 陈幸华; 刘耀; 高蕾; 曾韫璟; 张诚; 张曦

    2011-01-01

    目的 观察重组人粒细胞集落刺激因子(G-CSF)动员的供者外周血单个核细胞输注治疗异基因造血干细胞移植后,白血病复发的有效性及安全性.方法 对2009年7月至2011年2月该科20例异基因造血干细胞移植后复发的白血病患者,予以输注G-CSF动员后供者外周血单个核细胞.其中5例急性淋巴细胞白血病-CR2,8例急性髓系白血病-CR2,2例急性髓系白血病-CR3,3例急性混合细胞白血病,2例加速期慢性髓系白血病.在异基因造血干细胞移植后,半年内,20例患者均复发,予G-CSF动员后,供者外周血单个核细胞输注,每次输注细胞量按1×105/kg、2×105/kg、4×105/kg逐级增加,每次输注间隔4周.结果 12例患者再次完全缓解,8例患者未缓解.输注后,3例患者发生了Ⅰ~Ⅱ度急性移植物抗宿主病,12例患者发生了慢性移植物抗宿主病,5例未发生并发症,未观察到输注相关的全血细胞减少.结论 G-CSF动员供者外周血单个核细胞输注治疗异基因造血干细胞移植后,白血病复发有较好的疗效,不良反应小,值得临床进一步推广.%Objective To investigate the efficacy and safety of growth factor-primed donor hematopoietic stem cells infusion (GPBSCI)from donors stimulated with granulocyte colony-stimulating factor(G-CSF) in the treatment of patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods 20 cases of patients with relapsed leukemia,occurring in six months after allo-HSCT, among whom 5 cases were acute lymphoblastic leukemia(ALL) in CR2, 8 were acute myeloid leukemia(AML) in CR2,2 were AML in CR3,3 were acute mixed lineage leukemia(MAL) and 2 were chronic myeloid leu kemia at accelerated phase, received GPBSCI,during Jul. 2009 to Feb. 2011. The dose of cells infusion was 1 × l05/kg for the first time,2 × l05/kg for the second time,4 × l05/kg for the third time and so on, and the cells infusion was performed

  4. HLA-DP specific responses in allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated

  5. Study of a twisted ATLAS SCT Barrel deformation as revealed by a photogrammetric survey

    CERN Document Server

    Dobson, E; Heinemann, F; Karagoz-Unel, M

    2007-01-01

    A photogrammetry survey on the SCT barrels was performed as an engineering check on the structure of the ATLAS Semiconductor Tracker (SCT) shortly after construction. Analysis of the data obtained revealed small scale elliptical deformation as well as a twist of the structure. The results of the survey are presented as well as interpolation of the measured targets to the module positions and a comparison with track based alignment measurements.

  6. The ATLAS SCT endcap: From module production to commissioning

    Science.gov (United States)

    Ferrère, D.

    2007-01-01

    The ATLAS experiment at the Large Hadron Collider (LHC) at CERN is aiming for new physics at TeV scale energy and will be operational in 2007. The Semiconductor Tracker (SCT) is a part of the ATLAS Inner Detector (ID) and consists of 4088 silicon detector modules displayed on four concentric barrels and two endcaps on each side. Almost 2400 endcap modules have been produced in seven assembly sites including a 20% contingency. All the qualified modules have been shipped to the two macro-assembly sites where the modules are now mounted to the discs. A major organizational effort around the components and the logistics has been made to ensure that the project is running with a high yield and within the schedule. Well defined and strict quality assurance rules allowed the endcap community to achieve an average production yield of 92.9%. In order to complete the two endcaps, a major effort is made for finalizing the assembly of modules and services onto the discs and carbon fiber cylinder, respectively. After describing the organization of the endcap module assembly and the production results, a description and status of the endcap macro-assembly and services will be reported.

  7. Physical properties of the eclipsing Delta Sct star KIC 10661783

    CERN Document Server

    Lehmann, H; Tkachenko, A; Pavlovski, K

    2013-01-01

    KIC 10661783 is an eclipsing binary that shows Delta Sct-like oscillations. More than 60 pulsation frequencies have been detected in its light curve as observed by the Kepler satellite. We want to determine the fundamental stellar and system parameters of the eclipsing binary as a precondition for asteroseismic modelling of the pulsating component and to establish whether the star is a semi-detached Algol-type system. We measured the radial velocities of both components from new high-resolution spectra using TODCOR and compute the orbit using PHOEBE. We used the KOREL program to decompose the observed spectra into its components, and analysed the decomposed spectra to determine the atmospheric parameters. For this, we developed a new computer program for the normalisation of the KOREL output spectra. Fundamental stellar parameters are determined by combining the spectroscopic results with those from the analysis of the Kepler light curve. We obtain Teff, logg, vsini, and the absolute masses and radii of the c...

  8. The ATLAS SCT endcap: From module production to commissioning

    International Nuclear Information System (INIS)

    The ATLAS experiment at the Large Hadron Collider (LHC) at CERN is aiming for new physics at TeV scale energy and will be operational in 2007. The Semiconductor Tracker (SCT) is a part of the ATLAS Inner Detector (ID) and consists of 4088 silicon detector modules displayed on four concentric barrels and two endcaps on each side. Almost 2400 endcap modules have been produced in seven assembly sites including a 20% contingency. All the qualified modules have been shipped to the two macro-assembly sites where the modules are now mounted to the discs. A major organizational effort around the components and the logistics has been made to ensure that the project is running with a high yield and within the schedule. Well defined and strict quality assurance rules allowed the endcap community to achieve an average production yield of 92.9%. In order to complete the two endcaps, a major effort is made for finalizing the assembly of modules and services onto the discs and carbon fiber cylinder, respectively. After describing the organization of the endcap module assembly and the production results, a description and status of the endcap macro-assembly and services will be reported

  9. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies

    OpenAIRE

    Oudin, Claire; Chevallier, Patrice; Furst, Sabine; Guillaume, Thierry; Cheikh, Jean El; Delaunay, Jacques; Castagna, Luca; Faucher, Catherine; Granata, Angela; Devillier, Raynier; Chabannon, Christian; Esterni, Benjamin; Vey, Norbert; Mohty, Mohamad; Blaise, Didier

    2014-01-01

    The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m2/day for 5 days...

  10. Allogeneic Th1 Cells Home to Host Bone Marrow and Spleen and Mediate IFNγ-Dependent Aplasia

    OpenAIRE

    Chewning, Joseph H.; Zhang, Weiwei; Randolph, David A.; Swindle, C. Scott; Schoeb, Trenton R.; Weaver, Casey T.

    2013-01-01

    Bone marrow graft failure and poor graft function are frequent complications following hematopoietic stem cell transplantation and result in significant morbidity and mortality. Both conditions are associated with graft versus host disease (GVHD), although the mechanism remains undefined. Here we show in two distinct murine models of GVHD (complete MHC- and class II-disparate) that mimic human peripheral blood stem cell transplantation that Th1 CD4+ cells induce bone marrow failure in allogen...

  11. Hot off the press - First Combined SCT/TRT Endcap Cosmics Seen in SR1

    CERN Multimedia

    Christian Schmitt

    Following the successful combined SCT/TRT barrel test in the Spring 2006 (see ATLAS eNews from May 2006), a similar combined SCT/TRT endcap test is currently being performed in the SR1 building on the ATLAS experimental site at CERN. One quadrant of the SCT and two sectors of the TRT have been cabled up and are used in this test. The picture shows one of the first combined tracks seen in the cosmics runs. The data taking and combined testing is expected to last until December 11th. The event display below shows one of the first combined tracks seen in the cosmics run. There are three different views of the same event: the top left part shows a x-y view of the event where the track can be seen in red, the SCT spacepoints in green, and the SCT strips in grey. On the right is the z-phi view, where also the TRT DriftCircles can be seen as white dots. In the bottom window, the TRT wheels are on top and the SCT disks are shown below with the hits corresponding to those shown in the top window. The TRT DriftCircl...

  12. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    Science.gov (United States)

    Solmaz, Soner; Gereklioğlu, Çiğdem; Tan, Meliha; Demir, Şenay; Yeral, Mahmut; Korur, Aslı; Boğa, Can; Özdoğu, Hakan

    2015-01-01

    Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature. PMID:25912759

  13. A Rare Complication Developing After Hematopoietic Stem Cell Transplantation: Wernicke’s Encephalopathy

    Directory of Open Access Journals (Sweden)

    Soner Solmaz

    2015-12-01

    Full Text Available Thiamine is a water-soluble vitamin. Thiamine deficiency can present as a central nervous system disorder known as Wernicke’s encephalopathy, which classically manifests as confusion, ataxia, and ophthalmoplegia. Wernicke’s encephalopathy has rarely been reported following hematopoietic stem cell transplantation. Herein, we report Wernicke’s encephalopathy in a patient with acute myeloid leukemia who had been receiving prolonged total parenteral nutrition after haploidentical allogeneic hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case reported from Turkey in the literature.

  14. How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT.

    Science.gov (United States)

    Fuji, S; Rovó, A; Ohashi, K; Griffith, M; Einsele, H; Kapp, M; Mohty, M; Majhail, N S; Engelhardt, B G; Tichelli, A; Savani, B N

    2016-08-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients frequently develop glucose intolerance and post-transplant diabetes mellitus (PTDM). The clinical importance of PTDM and its detrimental impact on HSCT outcomes are under-recognized. After allo-HSCT, various mechanisms can contribute to the development of PTDM. Here we review information about hyperglycemia and PTDM after allo-HSCT as well as PTDM after solid organ transplantation and describe ways to manage hyperglycemia/PTDM after allogeneic HSCT. Taking into consideration a lack of well-established evidence in the field of allo-HSCT, more studies should be conducted in the future, which will require closer multidisciplinary collaboration between hematologists, endocrinologists and nutritionists. PMID:27042848

  15. Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice

    OpenAIRE

    Nijagal, Amar; Wegorzewska, Marta; Jarvis, Erin; Le, Tom; Tang, Qizhi; MacKenzie, Tippi C.

    2011-01-01

    Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we h...

  16. Music Therapy for Patients Who Have Undergone Hematopoietic Stem Cell Transplant

    OpenAIRE

    Ratcliff, Chelsea G.; Sarah Prinsloo; Michael Richardson; Laura Baynham-Fletcher; Richard Lee; Alejandro Chaoul; Cohen, Marlene Z; Marcos de Lima; Lorenzo Cohen

    2014-01-01

    Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT). Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching) based music therapy (MT; n = 29), unstructured music (UM; n = 30), or usual care (UC; n = 31) for four weeks. The ISO principle posits that patients may shift their mood from one state to another...

  17. Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation

    OpenAIRE

    KhalidAhmedAl-Anazi; ASMAMAL-JASSER; KhalidAlsaleh

    2014-01-01

    Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10–40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between

  18. Evaluating risk factors for Clostridium difficile infection in adult and pediatric hematopoietic cell transplant recipients

    OpenAIRE

    Boyle, Nicole M.; Magaret, Amalia; Stednick, Zach; Morrison, Alex; Butler-Wu, Susan; Zerr, Danielle; Rogers, Karin; Podczervinski, Sara; Cheng, Anqi; Wald, Anna; Pergam, Steven A

    2015-01-01

    Background Although hematopoietic cell transplant (HCT) recipients are routinely exposed to classic risk factors for Clostridium difficile infection (CDI), few studies have assessed CDI risk in these high-risk patients, and data are especially lacking for pediatric HCT recipients. We aimed to determine incidence and risk factors for CDI in adult and pediatric allogeneic HCT recipients. Methods CDI was defined as having diarrhea that tested positive for C. difficile via PCR, cytotoxin assay, o...

  19. Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution

    OpenAIRE

    Lee, Jae Hee; Yoon, Hoi Soo; Song, Joon Sup; Choi, Eun Seok; Moon, Hyung Nam; Seo, Jong Jin; Im, Ho Joon

    2009-01-01

    We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients...

  20. Results of a search for γ Dor and δ SCT stars with the Kepler spacecraft

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, P. A.; Miles, L. F. [XCP-6, MS F-699 Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Guzik, J. A. [XTD-NTA, MS T-086 Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Uytterhoeven, K. [Instituto de Astrofisica de Canarias, 38200 La Laguna, Tenerife, Spain and Departamento de Astrofisica, Universidad de La Laguna, E-38200 La Laguna, Tenerife (Spain); Jackiewicz, J. [New Mexico State University, Las Cruces, NM 88003 (United States); Kinemuchi, K., E-mail: pbradley@lanl.gov [Apache Point Observatory, Sunspot, NM 88349 (United States)

    2015-02-01

    The light curves of 2768 stars with effective temperatures and surface gravities placing them near the gamma Doradus (γ Dor)/delta Scuti (δ Sct) instability region were observed as part of the Kepler Guest Observer program from Cycles 1 through 5. The light curves were analyzed in a uniform manner to search for γ Dor, δ Sct, and hybrid star pulsations. The γ Dor, δ Sct, and hybrid star pulsations extend asteroseismology to stars slightly more massive (1.4–2.5 M{sub ⊙}) than our Sun. We find 207 γ Dor, 84 δ Sct, and 32 hybrid candidate stars. Many of these stars are cooler than the red edge of the γ Dor instability strip as determined from ground-based observations made before Kepler. A few of our γ Dor candidate stars lie on the hot side of the ground-based γ Dor instability strip. The hybrid candidate stars cover the entire region between 6200 K and the blue edge of the ground-based δ Sct instability strip. None of our candidate stars are hotter than the hot edge of the ground-based δ Sct instability strip. Our discoveries, coupled with the work of others, show that Kepler has discovered over 2000 γ Dor, δ Sct, and hybrid star candidates in the 116 square degree Kepler field of view. We found relatively few variable stars fainter than magnitude 15, which may be because they are far enough away to lie between spiral arms in our Galaxy, where there would be fewer stars.

  1. Amplitude modulation in δ Sct stars: statistics from an ensemble study of Kepler targets

    Science.gov (United States)

    Bowman, Dominic M.; Kurtz, Donald W.; Breger, Michel; Murphy, Simon J.; Holdsworth, Daniel L.

    2016-08-01

    We present the results of a search for amplitude modulation of pulsation modes in 983 δ Sct stars, which have effective temperatures between 6400 ≤ Teff ≤ 10 000 K in the Kepler Input Catalogue and were continuously observed by the Kepler Space Telescope for 4 yr. We demonstrate the diversity in pulsational behaviour observed, in particular non-linearity, which is predicted for δ Sct stars. We analyse and discuss examples of δ Sct stars with constant amplitudes and phases; those that exhibit amplitude modulation caused by beating of close-frequency pulsation modes; those that exhibit pure amplitude modulation (with no associated phase variation); those that exhibit phase modulation caused by binarity; and those that exhibit amplitude modulation caused by non-linearity. Using models and examples of individual stars, we demonstrate that observations of the changes in amplitude and phase of pulsation modes can be used to distinguish among the different scenarios. We find that 603 δ Sct stars (61.3 per cent) exhibit at least one pulsation mode that varies significantly in amplitude over 4 yr. Conversely, many δ Sct stars have constant pulsation amplitudes so short-length observations can be used to determine precise frequencies, amplitudes and phases for the most coherent and periodic δ Sct stars. It is shown that amplitude modulation is not restricted to a small region on the HR diagram, therefore not necessarily dependent on stellar parameters such as Teff or log g. Our catalogue of 983 δ Sct stars will be useful for comparisons to similar stars observed by K2 and TESS, because the length of the 4-yr Kepler data set will not be surpassed for some time.

  2. 酪氨酸激酶抑制剂联合异基因造血干细胞移植治疗费城染色体阳性急性淋巴细胞白血病的研究进展%Research progress of tyrosine kinase inhibitor combining with allogeneic hematopoietic stem cell transplantation in treatment of Philadelphia chromosome positive acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    王静静; 江明

    2016-01-01

    费城染色体阳性(Ph+)急性淋巴细胞白血病(ALL)是成年人ALL的常见类型.在酪氨酸激酶抑制剂(TKI)问世前,ph+是成年人ALL的不良预后因素之一.在TKI应用于Ph+ ALL治疗后显著改善其疗效,完全缓解(CR)率可达90%以上,缓解持续时间较前明显延长,从而使更多Ph+ ALL患者能够行异基因造血干细胞移植(allo-HSCT).采用以TKI为基础化疗获得CR后行allo-HSCT是Ph+ ALL患者的标准治疗方案.目前,移植前微小残留疾病(MRD)检测是否对该病的治疗具有临床指导意义,尚存争议.替代供者移植治疗Ph+ ALL在临床取得理想疗效,但需要前瞻性随机对照试验来证实其疗效.移植后联合TKI治疗可明显改善Ph+ ALL患者的长期生存,但其具体使用方案仍需多中心、大样本量的临床随机对照实验证实,而移植后复发仍是Ph+ ALL患者面临的难题之一.%Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is the most common type of adult acute lymphoblastic leukemia(ALL).Before the advent of tyrosine kinase inhibitors (TKI),Ph+ ALL carried a dismal prognosis.Outcomes for patients with Ph+ ALL improved substantially with the administration of TKI,and the TKI induced complete remissions(CR) in more than 90% patients,with remission duration prolonging,making more patients able to undergo allogeneic hematopoietic stem cell transplantation(allo-HSCT).Currently,TKI-based chemotherapy following allo-HSCT is established as the first-line strategy.Breakpoint cluster region-abelson leukemia virus(BCR-ABL) monitoring appears to relate to prognostic relevance and may be as guiding treatment before allo-HSCT,but clinical benefit is controversial in the TKI era.Alternative donor transplantation obtains promising effect in clinical practice,but needs more research.The administration of TKI after allo-HSCT may improve quality of life and prolong life span,but relapse remains a major problem of treatment failure

  3. Amplitude modulation in $\\delta$ Sct stars: statistics from an ensemble study of Kepler targets

    CERN Document Server

    Bowman, Dominic M; Breger, Michel; Murphy, Simon J; Holdsworth, Daniel L

    2016-01-01

    We present the results of a search for amplitude modulation of pulsation mode frequencies in 983 $\\delta$ Sct stars, which have effective temperatures between 6400 $\\leq T_{\\rm eff} \\leq$ 10 000 K in the Kepler Input Catalogue and were continuously observed by the Kepler Space Telescope for 4 yr. We demonstrate the diversity in pulsational behaviour observed, in particular nonlinearity, which is predicted for $\\delta$ Sct stars. We analyse and discuss examples of $\\delta$ Sct stars with constant amplitudes and phases; those that exhibit amplitude modulation caused by beating of close-frequency pulsation modes; those that exhibit pure amplitude modulation (with no associated phase variation); those that exhibit phase modulation caused by binarity; and those that exhibit amplitude modulation caused by nonlinearity. Using models and examples of individual stars, we demonstrate that observations of the changes in amplitude and phase of pulsation modes can be used to distinguish among the different scenarios. We f...

  4. Differentiating SCT and inattentive symptoms in ADHD using fMRI measures of cognitive control

    Directory of Open Access Journals (Sweden)

    Catherine Fassbender

    2015-01-01

    Full Text Available Attention Deficit/Hyperactivity Disorder (ADHD is associated with different impairment profiles in the symptom domains of hyperactivity/impulsivity and/or inattention. An additional symptom domain of sluggish cognitive tempo (SCT has also been proposed. Although there is a degree of correlation between the SCT symptom domain and inattention, it has been proposed as a distinct disorder independent of ADHD. The objective of this study was to examine the neural substrates of cue-related preparatory processes associated with SCT symptoms versus inattentive symptoms in a group of adolescents with ADHD. We also compared cue-related effects in the entire ADHD group compared with a group of typically developing (TD peers. A modified cued flanker paradigm and fMRI examined brain activity associated with attention preparation and motor response preparation. Between group contrasts between the ADHD and TD group revealed significant hypoactivity in the ADHD group during general attention preparation in the supplementary motor area (SMA and in the right superior parietal lobe (SPL during response preparation. In the ADHD group, greater numbers of SCT symptoms were associated with hypoactivity in the left SPL to cues in general whereas greater numbers of inattentive symptoms were associated with greater activity in the SMA to cues that provided no information and less activity in the thalamus during response preparation. Hypoactivity in the SPL with increasing SCT symptoms may be associated with impaired reorienting or shifting of attention. Altered activity in the SMA and thalamus with increasing inattention may be associated with a general problem with response preparation, which may also reflect inefficient processing of the response preparation cue. Our results support a degree of differentiation between SCT and inattentive symptom profiles within adolescents with ADHD.

  5. A snap-shot of a cosmic ray event seen in the different layers of both the SCT and TRT detectors.

    CERN Multimedia

    2006-01-01

    Clean tracks of cosmic rays were detected in the completed semiconductor tracker (SCT) and transition radiation tracker (TRT) barrels. These tracking tests come just months after the successful insertion of the SCT into the TRT

  6. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

    2014-09-15

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  7. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    International Nuclear Information System (INIS)

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  8. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation.

    Science.gov (United States)

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

    2015-01-01

    Prognosis of leukemia relapse post allogeneic stem cell transplantation (alloSCT) is poor and effective new treatments are urgently needed. T cells are pivotal in eradicating leukemia through a graft versus leukemia (GVL) effect and leukemia relapse is considered a failure of GVL. T-cell exhaustion is a state of T-cell dysfunction mediated by inhibitory molecules including programmed cell death protein 1 (PD-1) and T-cell immunoglobulin domain and mucin domain 3 (TIM-3). To evaluate whether T-cell exhaustion and inhibitory pathways are involved in leukemia relapse post alloSCT, we performed phenotypic and functional studies on T cells from peripheral blood of acute myeloid leukemia patients receiving alloSCT. Here we report that PD-1(hi)TIM-3(+) cells are strongly associated with leukemia relapse post transplantation. Consistent with exhaustion, PD-1(hi)TIM-3(+) T cells are functionally deficient manifested by reduced production of interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). In addition, these cells demonstrate a phenotype consistent with exhausted antigen-experienced T cells by losing TN and TEMRA subsets. Importantly, increase of PD-1(hi)TIM-3(+) cells occurs before clinical diagnosis of leukemia relapse, suggesting their predictive value. Results of our study provide an early diagnostic approach and a therapeutic target for leukemia relapse post transplantation. PMID:26230954

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

    International Nuclear Information System (INIS)

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

  10. HLA-DP specific responses in allogeneic stem cell transplantation

    OpenAIRE

    Rutten, Caroline Elisabeth

    2013-01-01

    Clinical studies demonstrated that HLA-DPB1 mismatched stem cell transplantation (SCT) is associated with a decreased risk of disease relapse and an increased risk of graft versus host disease (GVHD) compared to HLA-DPB1 matched SCT. In T-cell depleted SCT, mismatching of HLA-DPB1 was not associated with an increased risk of severe GVHD, whereas a significant decreased risk of disease relapse was still observed. In this thesis we showed that HLA-DPB1 mismatched allo-SCT followed by donor lymp...

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

    Directory of Open Access Journals (Sweden)

    Rosana M. Lamego

    2010-01-01

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

  12. The excitation of solar-like oscillations in a δ Sct star by efficient envelope convection

    DEFF Research Database (Denmark)

    Antoci, V.; Handler, G.; Kallinger, T.;

    2011-01-01

    Delta Scuti (δSct) stars are opacity-driven pulsators with masses of 1.5-2.5Msolar, their pulsations resulting from the varying ionization of helium. In less massive stars such as the Sun, convection transports mass and energy through the outer 30per cent of the star and excites a rich spectrum o...

  13. Temperature and radius variations in delta Sct, rho Pup and X Cae

    International Nuclear Information System (INIS)

    Low-resolution spectral measurements have been used to determine the temperature and relative radius variations in three pulsating stars of the delta Sct class. The variations in the radii of rho Pup and X Cae (HR 1653) are not quite in agreement with radial velocity measurements found in the literature, a discrepancy which may indicate that these stars pulsate aspherically. (author)

  14. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

    Science.gov (United States)

    Avery, R; Kalaycio, M; Pohlman, B; Sobecks, R; Kuczkowski, E; Andresen, S; Mossad, S; Shamp, J; Curtis, J; Kosar, J; Sands, K; Serafin, M; Bolwell, B

    2005-03-01

    Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant. PMID:15640812

  15. A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes

    OpenAIRE

    Locke, F; Agarwal, R.; Kunnavakkam, R; van Besien, K; Larson, RA; Odenike, O.; Godley, LA; Liu, H; Le Beau, MM; Gurbuxani, S; Thirman, MJ; Sipkins, D; White, C.; Artz, A; Stock, W.

    2013-01-01

    Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome (MDS) fare poorly following allogeneic hematopoietic cell transplant (HCT). We report prospective phase II study results of 29 patients given clofarabine 30 mg/m2/day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. A total of 15/29 patients (52%) were cytoreduced according to pre-defined criteria (cellularity < 20% and blasts < 10%). Marrow cellularity (P < 0.0001) and blast% ...

  16. The lung function score and its components as predictors of overall survival and chronic graft-vs-host disease after allogeneic stem cell transplantation

    OpenAIRE

    Ditz, Diana; Rabanus, Robert; Schulz, Christian; Wolff, Daniel; Holler, Barbara; HOLLER, ERNST; Hildebrandt, Gerhard Carl

    2016-01-01

    Aim To retrospectively assess if the modified lung function score (LFS) and/or its components, forced expiratory volume within the first second (FEV1) and diffusion capacity for carbon monoxide corrected for hemoglobin level (cDLCO), predict overall survival (OS) and chronic graft-vs-host-disease (cGvHD). Methods We evaluated 241 patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the University of Regensburg Transplant Center between June 1998 and July 2005 i...

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27103745

  18. Decreased Infections in Recipients of Unrelated Donor Hematopoietic Cell Transplantation from Donors with an Activating KIR Genotype

    OpenAIRE

    Tomblyn, Marcie; Young, Jo-Anne H.; Haagenson, Michael D.; Klein, John P.; Trachtenberg, Elizabeth A.; Storek, Jan; Spellman, Stephen R.; Cooley, Sarah; Miller, Jeffrey S.; Weisdorf, Daniel J.

    2010-01-01

    Infectious complications following allogeneic hematopoietic cell transplantation (HCT) from unrelated donors (URD) result in significant morbidity. We hypothesized that recipients of an URD with an activating natural killer cell immunoglobulin-like receptor (KIR) (B/x) genotype would have decreased infectious complications due to enhanced NK cell function. We compared the infectious complications in 116 recipients of a graft from a donor with an A/A KIR (n = 44) genotype and a B/x KIR (n = 72...

  19. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    Science.gov (United States)

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [ 25% decrement in GFR but twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with sepsis, liver and pulmonary dysfunction. The major fall in GFR occurred during chemotherapy but before hematopoietic cell support, thus

  20. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    Science.gov (United States)

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options. PMID:27026249

  1. Particle Physics and Astronomy Research Council (PPARC) members, United Kingdom, visiting the ATLAS semiconductor tracker (SCT) module tests.

    CERN Multimedia

    Patrice Loïez

    2002-01-01

    Photo 01: Mr Peter Warry, PPARC Chairman, Victrex Plc, United Kingdom visiting the ATLAS SCT module tests with Dr Joleen Pater, SCT (Manchester). Photo 02: PPARC Council Members, United Kingdom, visiting the ATLAS SCT module tests. L.t to r.: Mrs Judith Scott, Chief Executive, British Computer Society, Prof. George Efstathiou, Institute of Astronomy, University of Cambridge, Mr Peter Warry, PPARC Chairman, Victrex Plc, Prof. Martin Ward, Director X-Ray Astronomy, of Leicester, Prof. James Stirling, Director, Institute for Particle Physics Phenomenology, University of Durham and Prof. Brian Foster, University of Bristol.

  2. Chiaroscuro hematopoietic stem cell.

    OpenAIRE

    Quesenberry, P.; Habibian, M. (PhD); Dooner, M; Zhong, S.; Reilly, J; Peters, S.; De Becker, P; Grimaldi, C.; Carlson, J; REDDY, P; Nilsson, S.; Stewart, F. M.

    1998-01-01

    These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in ...

  3. Hematopoietic stem cell transplantation

    OpenAIRE

    Eleftheria Hatzimichael; Mark Tuthill

    2010-01-01

    Eleftheria Hatzimichael1, Mark Tuthill21Department of Haematology, Medical School of Ioannina, University of Ioannina, Ioannina, Greece; 2Department of Medical Oncology, Hammersmith Hospital, Imperial College National Health Service Trust, London, UKAbstract: More than 25,000 hematopoietic stem cell transplantations (HSCTs) are performed each year for the treatment of lymphoma, leukemia, immune-deficiency illnesses, congenital metabolic defects, hemoglobinopathies, and myelodysplastic and mye...

  4. Canine allogeneic bone marrow transplantation: technique and variables influencing engraftment

    International Nuclear Information System (INIS)

    We have studied the toxicity and immune suppression of supralethal total body irradiation (800-2000 rads, 60Co) at three dose intensities (10 rads/min, 49 rads/min, and 100 rads/min). In 79 intensively supported radiation control animals, the LD/sub 50(5)/ (that theoretical dose at which 50 percent of the animals will die within 5 days) for these dose intensities is estimated to be 1556, 941, and 921 rads, respectively. A biomodal pattern of early (median 4 days) and late (median 9 days) deaths was observed corresponding to histopathological evidence of the intestinal and hematopoietic radiation syndromes. Random donor bone marrow transplants were performed in 83 animals to test immune suppression afforded by 800 rads and 1000 rads at dose intensities of either 10 rads/min or 49 rads/min. Bone marrow cell dose was varied to analyze its effect on engraftment. A greater degree of immunosuppression with less toxicity was achieved at the lower dose intensity. A minimum dose of 3-5 x 108 nucleated allogeneic bone marrow cells/kg (readily obtainable from living donors) resulted in a high percentage of engraftment with lethal graft-versus-host disease following conditioning with 1,000 rads midplane at 10 rads/min, the optimum regimen employed

  5. End-of-Life Care Patterns Associated with Pediatric Palliative Care among Children Who Underwent Hematopoietic Stem Cell Transplant.

    Science.gov (United States)

    Ullrich, Christina K; Lehmann, Leslie; London, Wendy B; Guo, Dongjing; Sridharan, Madhumitha; Koch, Richard; Wolfe, Joanne

    2016-06-01

    Stem cell transplantation (SCT) is an intensive therapy offering the possibility of cure for life-threatening conditions but with risk of serious complications and death. Outcomes associated with pediatric palliative care (PPC) for children who undergo SCT are unknown. Therefore, we evaluated whether PPC consultation is associated with differences in end-of-life (EOL) care patterns for children who underwent SCT and did not survive. Medical records of children who underwent SCT at Boston Children's Hospital/Dana-Farber Cancer Institute for any indication from September 2004 to December 2012 and did not survive were reviewed. Child demographic and clinical characteristics and PPC consultation and EOL care patterns were abstracted. Children who received PPC (PPC group) were compared with those who did not (non-PPC group). Children who received PPC consultation (n = 37) did not differ from the non-PPC group (n = 110) with respect to demographic or clinical characteristics, except they were more likely to have undergone unrelated allogeneic SCT (PPC, 68%; non-PPC, 39%; P = .02) or to have died from treatment-related toxicity (PPC, 76%; non-PPC, 54%; P = .03). PPC consultation occurred at a median of .7 months (interquartile range [IQR], .4 to 4.2) before death. PPC consultations most commonly addressed goals of care/decision-making (92%), psychosocial support (84%), pain management (65%), and non-pain symptom management (70%). Prognosis discussions (ie, the likelihood of survival) occurred more commonly in the PPC group (PPC, 97%; non-PPC, 83%; P = .04), as did resuscitation status discussions (PPC, 88%; non-PPC, 58%; P = .002). These discussions also occurred earlier in the PPC group, for prognosis a median of 8 days (IQR, 4 to 26) before death compared with 2 days (IQR, 1 to 13) in the non-PPC group and for resuscitation status a median of 7 days (IQR, 3 to 18) compared with 2 days (IQR, 1 to 5) in the non-PPC group (P cure-oriented SCT setting, PPC

  6. Effectivity of a strategy in elderly AML patients to reach allogeneic stem cell transplantation using intensive chemotherapy: Long-term survival is dependent on complete remission after first induction therapy.

    Science.gov (United States)

    von dem Borne, P A; de Wreede, L C; Halkes, C J M; Marijt, W A F; Falkenburg, J H F; Veelken, H

    2016-07-01

    Intensive chemotherapy followed by allogeneic stem cell transplantation (alloSCT) can cure AML. Most studies on alloSCT in elderly AML report results of highly selected patient cohorts. Hardly any data exist on the effectiveness of prospective strategies intended to bring as many patients as possible to transplant. Between 2006 and 2011 we implemented a treatment algorithm for all newly diagnosed AML patients aged 61-75 years, consisting of intensive chemotherapy cycles to induce complete remission, followed by alloSCT. 44 of 60 (73%) newly diagnosed elderly AML patients started with chemotherapy. By meticulously following our algorithm in almost all patients, we could induce complete remission (CR) in 66% of patients starting with chemotherapy, and transplant 32% of these patients in continuous CR. Main reasons for failure were early relapse (16%), early death (14%), primary refractory disease (9%), and patient or physician decision to stop treatment (16%). Patients in continuous CR after first induction benefit most with 36% long-term survival. Patients not in CR after first induction benefit less; although additional chemotherapy induces CR in 45% of these patients, only 23% are transplanted and no long-term survival is observed, mainly due to relapse. Long-term survival in the group of 44 patients is 9% (median 4.5 years after alloSCT). Considering that 27% of patients do not start with chemotherapy and 64% of patients starting with chemotherapy do not reach alloSCT, the reasons for failure presented here should be used as a guide to develop new treatment algorithms to improve long-term survival in elderly AML patients. PMID:27123833

  7. Programming of donor T cells using allogeneic δ-like ligand 4-positive dendritic cells to reduce GVHD in mice.

    Science.gov (United States)

    Mochizuki, Kazuhiro; Meng, Lijun; Mochizuki, Izumi; Tong, Qing; He, Shan; Liu, Yongnian; Purushe, Janaki; Fung, Henry; Zaidi, M Raza; Zhang, Yanyun; Reshef, Ran; Blazar, Bruce R; Yagita, Hideo; Mineishi, Shin; Zhang, Yi

    2016-06-23

    Alloreactive T cells play a critical role in eliminating hematopoietic malignant cells but are also the mediators of graft-versus-host disease (GVHD), a major complication that subverts the success of allogeneic hematopoietic stem cell transplantation (HSCT). However, induction of alloreactive T cells does not necessarily lead to GVHD. Here we report the development of a cellular programming approach to render alloreactive T cells incapable of causing severe GVHD in both major histocompatibility complex (MHC)-mismatched and MHC-identical but minor histocompatibility antigen-mismatched mouse models. We established a novel platform that produced δ-like ligand 4-positive dendritic cells (Dll4(hi)DCs) from murine bone marrow using Flt3 ligand and Toll-like receptor agonists. Upon allogeneic Dll4(hi)DC stimulation, CD4(+) naïve T cells underwent effector differentiation and produced high levels of interferon γ (IFN-γ) and interleukin-17 in vitro, depending on Dll4 activation of Notch signaling. Following transfer, allogeneic Dll4(hi)DC-induced T cells were unable to mediate severe GVHD but preserved antileukemic activity, significantly improving the survival of leukemic mice undergoing allogeneic HSCT. This effect of Dll4(hi)DC-induced T cells was associated with their impaired expansion in GVHD target tissues. IFN-γ was important for Dll4(hi)DC programming to reduce GVHD toxicities of alloreactive T cells. Absence of T-cell IFN-γ led to improved survival and expansion of Dll4(hi)DC-induced CD4(+) T cells in transplant recipients and caused lethal GVHD. Our findings demonstrate that Dll4(hi)DC programming can overcome GVHD toxicity of donor T cells and produce leukemia-reactive T cells for effective immunotherapy. PMID:27143255

  8. Human cytomegalovirus antiviral drug resistance in hematopoietic stem cell transplantation: current state of the art.

    Science.gov (United States)

    Campos, Ana Bela; Ribeiro, Joana; Boutolleau, David; Sousa, Hugo

    2016-05-01

    Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients. The significant clinical impact of HCMV infection and progression to HCMV disease among allogeneic hematopoietic stem cell transplant recipients has been reduced by prophylactic, preemptive, and curative treatments using ganciclovir, valganciclovir, foscarnet, and cidofovir. Resistance to (val)ganciclovir results from mutations localized in HCMV UL97 gene (encoding the pUL97 phosphotransferase), UL54 gene (encoding the pUL54 DNA polymerase), or both genes, whereas foscarnet and cidofovir resistance results from mutations localized within UL54 gene only. This review is focused on HCMV antiviral drug resistance, including the functions of target genes of antivirals, the mechanisms of antiviral resistance, the different mutations in pUL97 and pUL54 that have been identified in either clinical isolates or laboratory strains, and their impact on HCMV susceptibility to antiviral drugs. It emphasizes the importance of proving that observed genetic changes confer resistance so they can be distinguished from polymorphisms. Because of the emergence of HCMV resistance to currently available drugs, novel drugs are urgently needed for the therapeutic management of HCMV-resistant infections in hematopoietic stem cell transplant patients. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26990717

  9. Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen

    OpenAIRE

    Maury, Sébastien; Bacigalupo, Andrea; Anderlini, Paolo; Aljurf, Mahmoud; Marsh, Judith; Socié, Gérard; Oneto, Rosi; Passweg, Jakob R

    2009-01-01

    Upfront or second line allogeneic hematopoietic stem cell transplantation (HSCT) offers a good disease-free survival option for patients suffering from severe idiopathic aplastic anemia. This report shows improved outcome of reduced-intensity versus conventional conditioning in HLA-identical sibling HSCT for older aplastic anemia patients.

  10. Performance And Radiation Hardness Of The Atlas/sct Detector Module

    CERN Document Server

    Eklund, L

    2003-01-01

    The ATLAS experiment is a general purpose experiment being constructed at the Large Hadron Collider (LHC) at FERN, Geneva. ATLAS is designed to exploit the full physics potential of LHC, in particular to study topics concerning the Higgs mechanism, Super-symmetry and CP violation. The cross sections for the processes under study are extremely small, requiring very high luminosity colliding beams. The Semiconductor Tracker (SCT) is an essential part of the Inner Detector tracking system of ATLAS. The active elements of the SCT is 4088 detector modules, tiled on four barrel cylinders and eighteen endcap disks. As a consequence of the high luminosity, the detector modules will operate in a harsh radiation environment. This thesis describes work concerning radiation hardness, beam test performance and methods for production testing of detector modules. The radiation hardness studies have been focused on the electrical performance of the front-end ASIC and the detector module. The results have identified features ...

  11. HD 41641: a classical $\\delta$ Sct-type pulsator with chemical signatures of an Ap star

    CERN Document Server

    Escorza, A; Tkachenko, A; Van Reeth, T; Ryabchikova, T; Neiner, C; Poretti, E; Rainer, M; Michel, E; Baglin, A; Aerts, C

    2016-01-01

    Among the known groups of pulsating stars, $\\delta$ Sct stars are one of the least understood. The theoretical models do not predict the oscillation frequencies that observations reveal. Complete asteroseismic studies are necessary to improve these models and better understand the internal structure of these targets. In this paper, we study the $\\delta$ Sct star HD 41641 with the ultimate goal of understanding its oscillation pattern. The target has been simultaneously observed by the CoRoT space telescope and the HARPS high-resolution spectrograph. The photometric data set was analyzed with the software package PERIOD04, while FAMIAS was used to analyze the line profile variations. The method of spectrum synthesis was used for spectroscopically determining the fundamental atmospheric parameters and the individual chemical abundances. A total of 90 different frequencies was identified and analyzed. An unambiguous identification of the azimuthal order of the surface geometry could be provided for the dominant ...

  12. The observation of Delta Sct and Gamma Dor stars by using MONS satellite

    CERN Document Server

    Zerbi, F M; Aerts, C; Handler, G; Kaye, A B

    2000-01-01

    The MONS space experiment will be able to verify some of the most important topics in the asteroseismologic studies of Delta Sct and Gamma Dor stars. We discuss how the $\\gamma$ Doradus can be considered possible "bridges" between the opacity driven overstable pulsation and the stochastically excited solar like oscillation. For this reason the possible inclusion of a Gamma Dor representative in the MONS main target list is presented and discussed. To study Delta Sct stars, an appropriate frequency resolution, comparable to or better than what is currently achieved by ground-based observations, is necessary and hence two runs are recommended. To avoid over-scheduling of the Main Camera, a possible combination of observations from the Main Camera and from the Star Trackers is proposed. As a result, key-objects could be adequately monitored, affording the possibility to enter into details of amplitude variations. Simultaneously, the same results could be obtained on two Gamma Dor stars.

  13. Associations between gastrointestinal toxicity, micro RNA and cytokine production in patients undergoing myeloablative allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Pontoppidan, Peter Erik Lotko; Jordan, Karina Kwi Im; Carlsen, Anting Liu;

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a procedure with a high risk of treatment related mortality. The primary aim of the present study was to examine associations between markers of gastrointestinal toxicity, markers of systemic inflammation, and plasma levels of micro......, lactulose-mannitol test and plasma citrulline, as a measure of the enterocyte population. Nadir of citrulline and maximum of oral toxicity scores, intestinal permeability, CRP and plasma levels of IL-6 and IL-10 was seen at day +7 post-HSCT. miRNA-155 and mi-RNA-146a showed an inverse relation with...

  14. HD 41641: A classical δ Sct-type pulsator with chemical signatures of an Ap star

    Science.gov (United States)

    Escorza, A.; Zwintz, K.; Tkachenko, A.; Van Reeth, T.; Ryabchikova, T.; Neiner, C.; Poretti, E.; Rainer, M.; Michel, E.; Baglin, A.; Aerts, C.

    2016-04-01

    Context. Among the known groups of pulsating stars, δ Sct stars are one of the least understood. Theoretical models do not predict the oscillation frequencies that observations reveal. Complete asteroseismic studies are necessary to improve these models and better understand the internal structure of these targets. Aims: We study the δ Sct star HD 41641 with the ultimate goal of understanding its oscillation pattern. Methods: The target was simultaneously observed by the CoRoT space telescope and the HARPS high-resolution spectrograph. The photometric data set was analyzed with the software package PERIOD04, while FAMIAS was used to analyze the line profile variations. The method of spectrum synthesis was used for spectroscopically determining the fundamental atmospheric parameters and individual chemical abundances. Results: A total of 90 different frequencies was identified and analyzed. An unambiguous identification of the azimuthal order of the surface geometry could only be provided for the dominant p-mode, which was found to be a nonradial prograde mode with m = +1. Using Teff and log g, we estimated the mass, radius, and evolutionary stage of HD 41641. We find HD 41641 to be a moderately rotating, slightly evolved δ Sct star with subsolar overall atmospheric metal content and unexpected chemical peculiarities. Conclusions: HD 41641 is a pure δ Sct pulsator with p-mode frequencies in the range from 10 d-1 to 20 d-1. This pulsating star presents chemical signatures of an Ap star and rotational modulation due to surface inhomogeneities, which we consider indirect evidence of the presence of a magnetic field. The CoRoT space mission was developed and operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain.This work uses ground-based spectroscopic observations made with the HARPS instrument at the 3.6 m-ESO telescope (La Silla, Chile) under the Large Program 185.D-0056.

  15. A comparison of HLA-identical sibling allogeneic versus autologous transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.

    Science.gov (United States)

    Lazarus, Hillard M; Zhang, Mei-Jie; Carreras, Jeanette; Hayes-Lattin, Brandon M; Ataergin, Asli Selmin; Bitran, Jacob D; Bolwell, Brian J; Freytes, César O; Gale, Robert Peter; Goldstein, Steven C; Hale, Gregory A; Inwards, David J; Klumpp, Thomas R; Marks, David I; Maziarz, Richard T; McCarthy, Philip L; Pavlovsky, Santiago; Rizzo, J Douglas; Shea, Thomas C; Schouten, Harry C; Slavin, Shimon; Winter, Jane N; van Besien, Koen; Vose, Julie M; Hari, Parameswaran N

    2010-01-01

    We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged >or=18 years undergoing first autologous (n = 837) or myeloablative (MA) allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for autologous HCT. Allogeneic HCT recipients were more likely to have high-risk disease features including higher stage, more prior chemotherapy regimens, and resistant disease. Allogeneic HCT was associated with a higher 1 year treatment-related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI], 3.21-7.40, P 50 years), lower performance score, chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk DLBCL patients, upfront MA allogeneic HCT, although associated with increased early mortality, was associated with a similar risk of disease progression compared to lower risk patients receiving autologous HCT. PMID:20053330

  16. 异基因造血干细胞移植后人类疱疹病毒6型感染及其与巨细胞病毒感染的相关性%Prevalence of Human Herpesvirus-6 in Allogeneic Hematopoietic Stem Cell Transplant Recipients in Correlation with Cytomegalovirus Infection

    Institute of Scientific and Technical Information of China (English)

    王立茹; 董陆佳; 陆道培

    2006-01-01

    为了解人类疱疹病毒6型(human herpesvirus 6, HHV-6)在中国接受异基因造血干细胞移植(hematopoietic stem cell transplantation, HSCT)的人群中感染现状及其与巨细胞病毒(cytomegalovirus, CMV)感染的相关性,对72例接受HSCT的患者HHV-6 DNA血症进行连续监测.收集HSCT患者移植前和移植后1-12周EDTA抗凝的外周血标本共680份,采用巢式聚合酶链反应检测外周血单个核细胞中HHV-6 DNA,并利用Hind Ⅲ限制性内切酶对HHV-6进行基因分型,同时采用免疫荧光法检测CMV抗原血症.结果显示,HSCT后62.5%(45/72)的患者至少1次出现HHV-6 DNA血症,首次检出的中位时间为14(7-63)天;除1例患者检出HHV-6A型以外,其余所有HHV-6阳性患者均为HHV-6B型感染.65.3%(47/72)的移植后患者至少1次发生CMV抗原血症,首次检出的中位时间为43(14-105)天.HHV-6与CMV共感染(CMV+/HHV-6+)的发生率为52.8%(38/72).HHV-6 DNA血症的首次检出时间早于CMV抗原血症(P<0.0001).HHV-6 DNA血症阳性患者CMV抗原血症检出率显著高于HHV-6血症阴性患者[84.4% (38/45) vs 33.3% (9/27), P=0.0001].HSCT后的疱疹病毒感染相关疾病中出血性膀胱炎(HC)发生率较高[23.6% (17/72)],其中88.2%(15/17)的HC发生于HHV-6血症阳性患者,82.3%(14/17)发生于CMV+/HHV-6+患者.结论:HSCT后HHV-6感染以及HHV-6与CMV共感染状态普遍存在,且发生于移植后早期的HHV-6感染与发生时间相对较晚的CMV感染之间可能存在相关性.

  17. COST OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN INDIA

    Directory of Open Access Journals (Sweden)

    Sanjeev Kumar Sharma

    2014-06-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is the definite cure for many hematological diseases. With the increasing indications for HSCT and its relatively low cost in Indian subcontinent, an increasing number of patients are opting for this procedure. We retrospectively analyzed the cost of one hundred sixty two HSCTs done at our center in the last three years. The median cost of autologous transplant was INR 7,52,294 (USD, $ 12,500 (range INR 6,19,850-14,17,212 and the median cost of allogenic transplant was INR 10,74,881 ($18,000 (range INR 6,49,944-23,82,227. The cost of HSCT is cheaper here compared to that in developed countries and success rates are nearly equivalent. The major factors contributing to the cost are related to the complications post-transplant mainly infections and graft versus host disease, which are also the reasons for the increased stay in the hospital.

  18. Iron Overload in Patients Undergoing Hematopoietic Stem Cell Transplantation

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    Vinod Pullarkat

    2010-01-01

    Full Text Available Recipients of hematopoietic stem cell transplantation (HSCT frequently have iron overload resulting from chronic transfusion therapy for anemia. In some cases, for example, in patients with myelodysplastic syndromes and thalassemia, this can be further exacerbated by increased absorption of iron from the gut as a result of ineffective erythropoiesis. Accumulating evidence has established the negative impact of elevated pretransplantation serum ferritin, a surrogate marker of iron overload, on overall survival and nonrelapse mortality after HSCT. Complications of HSCT associated with iron overload include increased bacterial and fungal infections as well as sinusoidal obstruction syndrome and possibly other regimen-related toxicities. Based on current evidence, particular attention should be paid to prevention and management of iron overload in allogeneic HSCT candidates, especially in patients with thalassemia and myelodysplastic syndromes. The pathophysiology of iron overload in the HSCT patient and optimum strategies to deal with iron overload during and after HSCT require further study.

  19. Allo-SCT for myelofibrosis: reversing the chronic phase in the JAK inhibitor era?

    Science.gov (United States)

    Tamari, R; Mughal, T I; Rondelli, D; Hasserjian, R; Gupta, V; Odenike, O; Fauble, V; Finazzi, G; Pane, F; Mascarenhas, J; Prchal, J; Giralt, S; Hoffman, R

    2015-05-01

    At present, allo-SCT is the only curative treatment for patients with myelofibrosis (MF). Unfortunately, a significant proportion of candidate patients are considered transplant ineligible due to their poor general condition and advanced age at the time of diagnosis. The approval of the first JAK inhibitor, ruxolitinib, for patients with advanced MF in 2011 has had a qualified impact on the treatment algorithm. The drug affords substantial improvement in MF-associated symptoms and splenomegaly but no major effect on the natural history. There has, therefore, been considerable support for assessing the drug's candidacy in the peritransplant period. The drug's precise impact on clinical outcome following allo-SCT is currently not known; nor are the drug's long-term efficacy and safety known. Considering the rarity of MF and the small proportion of patients who undergo allo-SCT, well designed collaborative efforts are required. In order to address some of the principal challenges, an expert panel of laboratory and clinical experts in this field was established, and an independent workshop held during the 54th American Society of Hematology Annual Meeting in New Orleans, USA on 6 December 2013, and the European Hematology Association's Annual Meeting in Milan, Italy on 13 June 2014. This document summarizes the results of these efforts. PMID:25665047

  20. Solid and Cystic Tumor (SCT of the Pancreas in an Adult Man

    Directory of Open Access Journals (Sweden)

    K. Ohiwa

    1997-01-01

    Full Text Available Solid and cystic tumor (SCT of the pancreas predominantly Occurs in women, and the occurrence in men is extremely rare. We experienced a male case of SCT. A 38-year-old man was admitted with the complaint of upper abdominal pain. CT scan showed the presence of a mass in the head of the pancreas. The mass was composed of high density areas and low density areas. Ultrasonograms revealed the mass being composed of high echoic areas and low echoic areas. The mass .was hypovascular on angiography. SCT was suspected and pancreaticoduodenectomy was performed. The cut surface of the tumor showed mainly cystic degenerative areas containing dark red hemorrhagic materials. Microscopically, there were solid areas in the periphery and pseudopapillary areas in the center. No metastasis was found in the removed lymph nodes. The tumor cells were not stained by Grimelius' silver stain. The tumor cells were positive for alpha-l-antitrypsin (AAT and neuron-specific enolase (NSE. Pancreatic hormones such as insulin, glucagon, and somatostatin were all negative. Electron micrograph showed that tumor cells were rich in mitochondria. Zymogen granules and neurosecretory granules were not detected. Estrogen receptor (ER and progesterone receptor (PR were both negative.

  1. Allogeneic radiation chimeras: long-term studies

    International Nuclear Information System (INIS)

    Lethally irradiated mice protected with allogeneic fetal liver cells or with syngeneic or allogeneic marrow and spleen cells treated with antisera to mouse immunoglobulins or to the T cell-associated 0 antigen and their controls were observed for up to 750 days. The best survival rates were found in the large groups given syngeneic marrow and spleen or allogeneic fetal liver cells (70-85 percent 700-day survival); in contrast, 43 percent of the group injected with allogeneic cells treated with anti-0 serum and 19 percent of those given antimmunoglobulin-treated cells were alive 700 days postradiation. Pulmonary infection was the most frequent cause of death of long-term survivors in all groups. Tumor incidence was increased in recipients of allogeneic cells (13 percent versus 4 percent among syngeneic chimeras), but the renal pathology seen in these groups was no greater than that noted in the syngeneic controls. Beginning 600 days after irradiation, mice from experimental and control groups were killed and their spleens were cultured with thymus-dependent antigens and the mitogens concanavalin Λ and lipopolysaccharide, Escherichia coli. The most frequent finding in all groups was mild to moderate impairment of T cell-dependent responses. (U.S.)

  2. Oral Complications in Hematopoietic Stem Cell Recipients: The Role of Inflammation

    Directory of Open Access Journals (Sweden)

    T. M. Haverman

    2014-01-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and in some cases with increased mortality and may significantly affect quality of life, even many years after HSCT. Inflammatory processes are key in the pathobiology of most oral complications in HSCT recipients. This review article will discuss frequently encountered oral complications associated with HSCT focusing on the inflammatory pathways and inflammatory mediators involved in their pathogenesis.

  3. Acute myeloid leukemia of donor origin after allogeneic stem cell transplantation from a sibling who harbors germline XPD and XRCC3 homozygous polymorphisms

    Directory of Open Access Journals (Sweden)

    da Silva Dayse A

    2011-09-01

    Full Text Available Abstract A 54-year-old woman was diagnosed with infiltrative ductal breast carcinoma. Two years after treatment, the patient developed an acute myeloid leukemia (AML which harbored del(11q23 in 8% of the blast cells. The patient was submitted for allogeneic stem cell transplantation (aSCT from her HLA-compatible sister. Ten months after transplantation, she relapsed with an AML with basophilic maturation characterized by CD45low CD33high, CD117+, CD13-/+, HLA Drhigh, CD123high, and CD203c+ blast cells lacking expression of CD7, CD10, CD34, CD15, CD14, CD56, CD36, CD64, and cytoplasmic tryptase. Karyotype analysis showed the emergence of a new clone with t(2;14 and FISH analysis indicated the presence of MLL gene rearrangement consistent with del(11q23. Interestingly, AML blast cell DNA tested with microsatellite markers showed the same pattern as the donor's, suggesting that this AML emerged from donor cells. Additionally, polymorphisms of the XPA, XPD, XRCC1, XRCC3 and RAD51 DNA repair genes revealed three unfavorable alleles with low DNA repair capacity. In summary, we report the first case of AML involving XPD and XRCC3 polymorphisms from donor origin following allogeneic stem cell transplantation and highlight the potential need for careful analysis of DNA repair gene polymorphisms in selecting candidate donors prior to allogeneic stem cell transplantation.

  4. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia in Adults.

    Science.gov (United States)

    Speziali, Craig; Paulson, Kristjan; Seftel, Matthew

    2016-06-01

    The majority of adults with acute lymphoblastic leukemia will achieve a first complete remission (CR). However relapse is the most common cause of treatment failure. Outcomes after relapse remain poor, with long-term survival in the order of 10 %. Treatment decisions made at the time of first complete remission are thus critical to ensuring long-term survival. Allogeneic hematopoietic cell transplant (HCT) is effective at preventing relapse in many transplant recipients but is also associated with significant treatment related morbidity and mortality. Alternatively, ongoing systemic chemotherapy offers lower toxicity at the expense of increased relapse rates. Over the past decades, both the safety of transplant and the efficacy of non-transplant chemotherapy have improved. Emerging data show substantially improved outcomes for young adults treated with pediatric-inspired chemotherapy regimens that question the role of HCT in the upfront setting. In this review, we review the data supporting the role of allogeneic transplantation in adult acute lymphoblastic leukemia (ALL), and we propose a therapeutic algorithm for upfront therapy of adults with ALL. PMID:26984203

  5. Genetic Modification of Hematopoietic Stem Cells as a Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Patrick Younan

    2013-11-01

    Full Text Available The combination of genetic modification and hematopoietic stem cell (HSC transplantation may provide the necessary means to develop an alternative treatment option to conventional antiretroviral therapy. As HSCs give rise to all hematopoietic cell types susceptible to HIV infection, modification of HSCs is an ideal strategy for the development of infection-resistant immune cell populations. Although promising results have been obtained in multiple animal models, additional evidence is needed to convincingly demonstrate the feasibility of this approach as a treatment of HIV-1 infected patients. Here, we review the potential of HSC transplantation and the recently identified limitations of this approach. Using the Berlin Patient as a model for a functional cure, we contrast the confines of autologous versus allogeneic transplantation. Finally, we suggest that although autologous, gene-modified HSC-transplantation may significantly reduce plasma viremia, reaching the lower detection limits currently obtainable through daily HAART will remain a challenging endeavor that will require innovative combinatorial therapies.

  6. Oral changes in individuals undergoing hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Regina Haddad Barrach

    2015-04-01

    Full Text Available INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression.OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation.METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients; B (autologous transplant, 31 patients. A total of three dental status assessments were performed: in the pre-transplantation period (moment 1, one week after stem cell infusion (moment 2, and 100 days after transplantation (moment 3. In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks.RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression.CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications.

  7. Engraftment of allogeneic dog bone marrow

    International Nuclear Information System (INIS)

    Resistance to allogeneic bone-marrow grafts (AR) was found to occur in many species, including the dog. The i.v. administration of silica particles suppressed Ar in vivo in this species. Genetic studies provide suggestive evidence for the existence of a previously unrecognized system or systems in the canine major histocompatibility complex controlling AR

  8. Comparison of the effects of salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) in a number of in vivo and in vitro tests

    Energy Technology Data Exchange (ETDEWEB)

    Welch, S.P.; Brase, D.; Cooper, C.; Dewey, W.L.

    1986-03-05

    sCT and CGRP have been shown previously to have multiple activities in the central nervous system (CNS). Recent work has shown that CGRP (15 ..mu..g) intraventricularly (IVT) produces a naloxone reversible 37% inhibition in the p-phenylquinone test (PPQ) accompanied by severe diarrhea. The ED50 of sCT in the PPQ test is 362 ng and this effect is not reversed totally by naloxone. The onset of CGRP is more rapid than that of sCT. sCT and CGRP (10/sup -6/M) both produce naloxone reversible inhibition of the electrically stimulated guinea pig ileum (GPI) (25% and 50% respectively). Both sCT and CGRP (10/sup -6/ M) produce contracture (15% and 40% respectively) of the non-stimulated GPI that is not blocked by atropine. Both sCT and CGRP block the naloxone-induced contracture of the morphine (MS04) dependent ilea (29% and 68% respectively). Both sCT and CGRP produce biphasic shifts in the MS04 acetylcholine dose-effect curves in the stimulated and nonstimulated GPI, respectively. Neither sCT nor CGRP (10/sup -9/ to 10/sup -4/ M) displaces /sup 3/H-naloxone binding to mouse brain membranes. Both sCT and CGRP may produce their effects by modulation of CA/sup +2/ fluxes in the CNS and GPI.

  9. Comparison of the effects of salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) in a number of in vivo and in vitro tests

    International Nuclear Information System (INIS)

    sCT and CGRP have been shown previously to have multiple activities in the central nervous system (CNS). Recent work has shown that CGRP (15 μg) intraventricularly (IVT) produces a naloxone reversible 37% inhibition in the p-phenylquinone test (PPQ) accompanied by severe diarrhea. The ED50 of sCT in the PPQ test is 362 ng and this effect is not reversed totally by naloxone. The onset of CGRP is more rapid than that of sCT. sCT and CGRP (10-6M) both produce naloxone reversible inhibition of the electrically stimulated guinea pig ileum (GPI) (25% and 50% respectively). Both sCT and CGRP (10-6 M) produce contracture (15% and 40% respectively) of the non-stimulated GPI that is not blocked by atropine. Both sCT and CGRP block the naloxone-induced contracture of the morphine (MS04) dependent ilea (29% and 68% respectively). Both sCT and CGRP produce biphasic shifts in the MS04 acetylcholine dose-effect curves in the stimulated and nonstimulated GPI, respectively. Neither sCT nor CGRP (10-9 to 10-4 M) displaces 3H-naloxone binding to mouse brain membranes. Both sCT and CGRP may produce their effects by modulation of CA+2 fluxes in the CNS and GPI

  10. Hematopoietic stem cell transplantation for infantile osteopetrosis.

    Science.gov (United States)

    Orchard, Paul J; Fasth, Anders L; Le Rademacher, Jennifer; He, Wensheng; Boelens, Jaap Jan; Horwitz, Edwin M; Al-Seraihy, Amal; Ayas, Mouhab; Bonfim, Carmem M; Boulad, Farid; Lund, Troy; Buchbinder, David K; Kapoor, Neena; O'Brien, Tracey A; Perez, Miguel A Diaz; Veys, Paul A; Eapen, Mary

    2015-07-01

    We report the international experience in outcomes after related and unrelated hematopoietic transplantation for infantile osteopetrosis in 193 patients. Thirty-four percent of transplants used grafts from HLA-matched siblings, 13% from HLA-mismatched relatives, 12% from HLA-matched, and 41% from HLA-mismatched unrelated donors. The median age at transplantation was 12 months. Busulfan and cyclophosphamide was the most common conditioning regimen. Long-term survival was higher after HLA-matched sibling compared to alternative donor transplantation. There were no differences in survival after HLA-mismatched related, HLA-matched unrelated, or mismatched unrelated donor transplantation. The 5- and 10-year probabilities of survival were 62% and 62% after HLA-matched sibling and 42% and 39% after alternative donor transplantation (P = .01 and P = .002, respectively). Graft failure was the most common cause of death, accounting for 50% of deaths after HLA-matched sibling and 43% of deaths after alternative donor transplantation. The day-28 incidence of neutrophil recovery was 66% after HLA-matched sibling and 61% after alternative donor transplantation (P = .49). The median age of surviving patients is 7 years. Of evaluable surviving patients, 70% are visually impaired; 10% have impaired hearing and gross motor delay. Nevertheless, 65% reported performance scores of 90 or 100, and in 17%, a score of 80 at last contact. Most survivors >5 years are attending mainstream or specialized schools. Rates of veno-occlusive disease and interstitial pneumonitis were high at 20%. Though allogeneic transplantation results in long-term survival with acceptable social function, strategies to lower graft failure and hepatic and pulmonary toxicity are urgently needed. PMID:26012570

  11. Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

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    Michaela Döring

    2012-01-01

    Full Text Available Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day and caspofungin (CAS, 50 mg/day during the first allogeneic hematopoietic stem cell transplantation (HSCT improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

  12. Exposure to whole body phantom using head and neck CT-unit (SCT-100N)

    International Nuclear Information System (INIS)

    In April 1979, our hospital was installed with home-made head CT-unit (SCT-100 N) and recently computed tomography (called CT) became very popular. In this study the absorbed dose distribution in the body phantom undergoing head scanning with the EMI-CT equipment was measured using a thermoluminescence dosimeter. It has been reported that the maximum absorbed dose of the brain was 1946 mrads per scan and the surface doses at the wrist and the foot seemed to range from 0.1 - 0.6 mrads and 1.7 - 5.3 mrads per scan, respectively. (author)

  13. The Thermal and Mechanical Properties of Glues for the ATLAS SCT ModuleAssembly

    CERN Document Server

    Kholodenko, A G; Riadovikov, VN

    2000-01-01

    We perform measurements of $C_{kt}-$the coefficient of thermal conductivityof two types of glue proposed for using in mechanical structureof the SCT modules of ATLAS .We compare the thermal property of thecommonly used electronic industry applications glue familyARALDITE and $Si-organic$ glue ``ELASTOSIL 137-182'' .The coefficients of the thermal conductivity for Boron nitride filled ARALDITE 1102 and ELASTOSIL 137-182 are presented. The value of the strength at tension was tested. The main results of the our tests are in agreement withvalues specified by manufacturer.

  14. Interactions between the gut microbiota, short-chain fatty acids and the immune system in pediatric patients undergoing hematopoietic stem cell transplantation

    OpenAIRE

    Nastasi, Claudia

    2015-01-01

    The gut microbiota (GM) is essential for human health and contributes to several diseases; indeed it can be considered an extension of the self and, together with the genetic makeup, determines the physiology of an organism. In this thesis has been studied the peripheral immune system reconstitution in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (aHSCT) in the early phase; in parallel, have been also explored the gut microbiota variations as one of the...

  15. Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR

    OpenAIRE

    Aranha Francisco JP; Vigorito Afonso C.; Oliveira Cristiane de; Albuquerque Dulcinéia M; Bonon Sandra HA; Andrade Paula D; Costa Cláudia RC; Peres Renata MB; de Souza Cármino A; Costa Sandra CB

    2010-01-01

    Abstract Background Human cytomegalovirus (CMV) infection still causes significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Therefore, it is extremely important to diagnosis and monitor active CMV infection in HSCT patients, defining the CMV DNA levels of virus replication that warrant intervention with antiviral agents in order to accurately prevent CMV disease and further related complications. Methods During the first 150 days after allogenei...

  16. Adverse Fat Depots and Marrow Adiposity Are Associated with Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation

    OpenAIRE

    MOSTOUFI-MOAB, SOGOL; Magland, Jeremy; Isaacoff, Elizabeth J.; Sun, Wenli; Rajapakse, Chamith S.; Zemel, Babette; Wehrli, Felix; Shekdar, Karuna; Baker, Joshua; Long, Jin; Leonard, Mary B.

    2015-01-01

    Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12–25 years) a median of 9.7 (4...

  17. Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin

    International Nuclear Information System (INIS)

    Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice

  18. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    International Nuclear Information System (INIS)

    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.

  19. 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.

  20. Thrombopoietin and hematopoietic stem cells

    OpenAIRE

    de Graaf, Carolyn A.; Metcalf, Donald

    2011-01-01

    Thrombopoietin (TPO) is the cytokine that is chiefly responsible for megakaryocyte production but increasingly attention has turned to its role in maintaining hematopoietic stem cells (HSCs). HSCs are required to initiate the production of all mature hematopoietic cells, but this differentiation needs to be balanced against self-renewal and quiescence to maintain the stem cell pool throughout life. TPO has been shown to support HSC quiescence during adult hematopoiesis, with the loss of TPO s...

  1. Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell Transplantation: Blood and Marrow Transplant Clinical Trials Network Protocol

    OpenAIRE

    Yanik, Gregory A.; Horowitz, Mary M.; Weisdorf, Daniel J.; Logan, Brent R.; Ho, Vincent T.; Soiffer, Robert J.; Carter, Shelly L.; Wu, Juan; Wingard, John R.; DiFronzo, Nancy L.; Ferrara, James L.; Giralt, Sergio; Madtes, David K.; Drexler, Rebecca; White, Eric S.

    2014-01-01

    Idiopathic pneumonia syndrome (IPS) is a diffuse, noninfectious lung injury that occurs acutely after allogeneic hematopoietic cell transplantation (HCT). IPS-related mortality has been historically high (>50%) despite treatment with systemic corticosteroids and supportive care measures. We have now examined the role of tumor necrosis factor inhibition in a randomized, double-blind, placebo-controlled trial of corticosteroids with etanercept or placebo. Thirty-four subjects (≥18 years) with I...

  2. Treatment of Oral Mucositis in Hematologic Patients Undergoing Autologous or Allogeneic Transplantation of Peripheral Blood Stem Cells: a Prospective, Randomized Study with a Mouthwash Containing Camelia Sinensis Leaf Extract

    OpenAIRE

    Giovanni Carulli; Melania Rocco; Alessia Panichi; Chiara Feira Chios; Ester Ciurli; Chiara Mannucci; Elisabetta Sordi; Francesco Caracciolo; Federico Papineschi; Edoardo Benedetti; Mario Petrini

    2013-01-01

    Oral mucositis is an important side effect of hematopoietic stem cell transplantation (HCST), mainly due to toxicity of conditioning regimens. It produces significant pain and morbidity. The present study reports a prospective, randomized, non-blinded study testing the efficacy of a new mouthwash, called Baxidil Onco® (Sanitas Farmaceutici Srl, Tortona, Italy) in 60 hematologic patients undergoing HCST (28 autologous, 32 allogeneic). Baxidil Onco®, used three times a day from Day -1 to Day +3...

  3. Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission.

    Directory of Open Access Journals (Sweden)

    Cornelis R van der Torren

    Full Text Available Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT. However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.

  4. HD 50844: the new look of Delta Sct stars from CoRoT space photometry

    CERN Document Server

    Poretti, E; Garrido, R; Lefèvre, L; Mantegazza, L; Rainer, M; Rodríguez, E; Uytterhoeven, K; Amado, P J; Martin-Ruiz, S; Moya, A; Niemczura, E; Suárez, J C; Zima, W; Baglin, A; Auvergne, M; Baudin, F; Catala, C; Samadi, R; Alvarez, M; Mathias, P; Paparo, M; Papics, P; Plachy, E

    2009-01-01

    It has also been suggested that the detection of a wealth of very low amplitude modes in Delta Sct stars was only a matter of signal--to--noise ratio. Access to this treasure, impossible from the ground, is one of the scientific aims of the space mission CoRoT, a space mission developed and operated by CNES. This work presents the results obtained on HD 50844: the 140,016 datapoints were analysed using independent approaches and several checks performed. A level of 10^{-5} mag was reached in the amplitude spectra of the CoRoT timeseries. The frequency analysis of the CoRoT timeseries revealed hundreds of terms in the frequency range 0--30 d^{-1}. All the cross--checks confirmed this new result. The initial guess that Delta Sct stars have a very rich frequency content is confirmed. The spectroscopic mode identification gives theoretical support since very high--degree modes (up to ell=14) are identified. We also prove that cancellation effects are not sufficient in removing the flux variations associated to th...

  5. Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

    Science.gov (United States)

    Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

    2016-10-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients. PMID:27465155

  6. Nutritional assessment as predictor of complications after hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Marcela Espinoza

    2016-02-01

    Full Text Available ABSTRACT Introduction: Nutritional support is pivotal in patients submitted to hematopoietic stem cell transplantation. Nutritional status has been associated with time of engraftment and infection rates. In order to evaluate the association between nutritional parameters and clinical outcomes after transplantation a cohort of transplant patients was retrospectively evaluated. Methods: All 50 patients transplanted between 2011 and 2014 were included. The nutritional status before transplantation, ten days after transplantation and before discharge was assessed including anthropometry, body mass index, albumin, prealbumin and total urinary nitrogen. Results: The median follow-up time was 41 months and the median age of patients was 41 years. Thirty-two underwent allogeneic and 18 autologous transplants. Diagnoses included acute leukemias (n = 27, lymphoma (n = 7, multiple myeloma (n = 13, and aplastic anemia (n = 3. Thirty-seven patients developed mucositis (three Grade 1, 15 Grade 2, 18 Grade 3 and one Grade 4, and twenty-two allogeneic, and five autologous transplant patients required total parenteral nutrition. Albumin and total urinary nitrogen were associated with length of hospital stay and platelet and neutrophil engraftment. None of the nutritional parameters evaluated were associated with overall survival. Non-relapse mortality was 14% and overall survival was 79% at 41 months of follow-up. Conclusions: After hematopoietic stem cell transplantation, high catabolism was associated with longer length of hospital stay, the need of total parenteral nutrition and platelet and neutrophil engraftment times. Nutritional parameters were not associated with overall survival.

  7. Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective.

    Science.gov (United States)

    Saraceni, F; Shem-Tov, N; Olivieri, A; Nagler, A

    2015-07-01

    Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34(+) stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34(+)/CD38(-) stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant. PMID:25665044

  8. Allogeneic radiation chimeras induced in SPF mice

    International Nuclear Information System (INIS)

    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.)

  9. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies

    Science.gov (United States)

    2016-08-15

    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  10. Phase I-II Study of Clofarabine-Melphalan-Alemtuzumab Conditioning for Allogeneic Hematopoietic Cell Transplantation

    OpenAIRE

    van Besien, Koen; Stock, Wendy; Rich, Elizabeth; Odenike, Olatoyosi; Godley, Lucy A.; O’Donnell, Peter H.; Kline, Justin; Nguyen, Vu; del Cerro, Paula; LARSON, RICHARD A.; Artz, Andrew S.

    2011-01-01

    We conducted a phase I-II study of transplantation conditioning with clofarabine-melphalan-alemtuzumab for patients with advanced hematologic malignancies. Ten patients were accrued to the phase I portion, which utilized an accelerated titration design. No dose-limiting toxicity was observed, and clofarabine 40 mg/m2 × 5, melphalan 140 mg/m2 × 1, and alemtuzumab 20 mg × 5 was adopted for the phase II study, which accrued 72 patients. Median age was 54 years. There were 44 patients with acute ...

  11. Study of Pulmonary Complications in Pediatric Patients With Storage Disorders Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Science.gov (United States)

    2005-06-23

    I Cell Disease; Fucosidosis; Globoid Cell Leukodystrophy; Adrenoleukodystrophy; Mannosidosis; Niemann-Pick Disease; Pulmonary Complications; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Metachromatic Leukodystrophy; Gaucher's Disease; Wolman Disease

  12. Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Amr Nassar

    2014-01-01

    Full Text Available Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals.

  13. Risk factors of CMV replication after allogeneic hematopoietic stem cell transplantation in children and adolescents

    Directory of Open Access Journals (Sweden)

    S. N. Shiriaev

    2014-09-01

    Full Text Available Risk factors of CMV replication in early period after allo-HSCT (D0‑D100 were – myeloablative conditioning – HR 3.74 (1.67–8.37, р = 0.001; unrelated donor – HR 2.18 (0.86–5.26, р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06, р = 0,06. In late posttransplant period (from D+100 significant risk factors of CMV-reactivation were (according to multivariate analysis myeloablative conditioning – HR 13.17 (3.00–57.86, р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50, р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50, р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19, р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92, р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08, р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17, р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.

  14. Risk factors of CMV replication after allogeneic hematopoietic stem cell transplantation in children and adolescents

    Directory of Open Access Journals (Sweden)

    S. N. Shiriaev

    2014-01-01

    Full Text Available Risk factors of CMV replication in early period after allo-HSCT (D0‑D100 were – myeloablative conditioning – HR 3.74 (1.67–8.37, р = 0.001; unrelated donor – HR 2.18 (0.86–5.26, р = 0.10; HLA-matched donor – HR 0.24 (0.05–1.06, р = 0,06. In late posttransplant period (from D+100 significant risk factors of CMV-reactivation were (according to multivariate analysis myeloablative conditioning – HR 13.17 (3.00–57.86, р = 0.001; combination of pretransplant remission of leukemia and using cyclosporine and methotrexate – HR 0.13 (0.03–0.50, р = 0.003; combination of aGVHD and CMV reactivation in early posttransplant period – HR 2.71 (0.86–8.50, р = 0.088; using of bone marrow – HR 0.37 (0.12–1.19, р = 0.095. We revealed the significant association of aGVHD and CMV-reactivation –OR 2.91 (1.07–7.92, р=0.006, and increased rate of cGVHD in patients with CMV replication at third month after allo-HSCT OR – 2.29 (1.03–5.08, р = 0.066. We revealed a tend to decreasing relapse risk in patients who had CMV-replication – HR 0.07 (0.004–1.17, р = 0.06. Cumulative incidence of CMV-disease was 28 %. CMV-disease was lethal in 44 % patients.

  15. Incidence of venous thromboembolism in the setting of hematopoietic cell transplantation.

    Science.gov (United States)

    O'Hara, V J Daphne; Miller, Trent; Mehta, Rakesh; Swartzendruber, Evonne; Kiel, Patrick J

    2014-01-01

    The underlying risk of venous thromboembolism (VTE) is unclear in patients undergoing hematopoietic cell transplantation (HCT). As such, these patients should still be considered at risk for development of VTE due to factors such as their underlying malignancy and the marked inflammatory state that develops from treatment. The purpose of this study was to characterize the incidence of VTE in patients undergoing HCT. Retrospective chart review of patients from the Indiana University Stem Cell Transplant Unit treated between January 1, 2008, and May 24, 2011. Patients were older than 18 years and had undergone HCT. The primary objective was to analyze the incidence of VTE in patients undergoing autologous HCT versus allogeneic HCT. Secondary objectives included documentation of VTE treatment strategies and time to occurrence of VTE. Of the 567 patients who underwent autologous HCT, 14 developed VTE (2.5%), whereas 5 of the 180 patients who underwent allogeneic HCT developed VTE (2.8%; P = 1.000). The median time to development of VTE from admission for HCT was 12 days in the autologous HCT arm versus 19 days in the allogeneic HCT arm (P = 0.610). The most commonly used VTE treatment strategy was enoxaparin (12 out of 19 VTEs). This study illustrates that VTE does occur rarely in patients who have undergone HCT. The optimal treatment regimen in this population requires further evaluation. Until a reliable protocol for treatment and evidence for risk factors are established, providers should be vigilant for occurrence of VTE in these patients. PMID:24061558

  16. Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.

    Science.gov (United States)

    Nguyen, Hung D; Chatterjee, Shilpak; Haarberg, Kelley M K; Wu, Yongxia; Bastian, David; Heinrichs, Jessica; Fu, Jianing; Daenthanasanmak, Anusara; Schutt, Steven; Shrestha, Sharad; Liu, Chen; Wang, Honglin; Chi, Hongbo; Mehrotra, Shikhar; Yu, Xue-Zhong

    2016-04-01

    Alloreactive donor T cells are the driving force in the induction of graft-versus-host disease (GVHD), yet little is known about T cell metabolism in response to alloantigens after hematopoietic cell transplantation (HCT). Here, we have demonstrated that donor T cells undergo metabolic reprograming after allogeneic HCT. Specifically, we employed a murine allogeneic BM transplant model and determined that T cells switch from fatty acid β-oxidation (FAO) and pyruvate oxidation via the tricarboxylic (TCA) cycle to aerobic glycolysis, thereby increasing dependence upon glutaminolysis and the pentose phosphate pathway. Glycolysis was required for optimal function of alloantigen-activated T cells and induction of GVHD, as inhibition of glycolysis by targeting mTORC1 or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) ameliorated GVHD mortality and morbidity. Together, our results indicate that donor T cells use glycolysis as the predominant metabolic process after allogeneic HCT and suggest that glycolysis has potential as a therapeutic target for the control of GVHD. PMID:26950421

  17. Predictive impact of allele-matching and EBMT risk score for outcome after T-cell depleted unrelated donor transplantation in poor-risk acute leukemia and myelodysplasia

    NARCIS (Netherlands)

    Lodewyck, T.; Oudshoorn, M.; Holt, B. van der; Petersen, E.; Spierings, E.; Borne, P. von dem; Schattenberg, A.V.M.B.; Allebes, W.A.; Groenendijk-Sijnke, M.; Duinhouwer, L.; Willemze, R.; Lowenberg, B.; Verdonck, L.F.; Meijer, E.; Cornelissen, J.J.

    2011-01-01

    Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease st

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. The acute impact of a hematopoietic allograft on lung function and inflammation: a prospective observational study

    Directory of Open Access Journals (Sweden)

    Enocson Alexandra

    2013-01-01

    Full Text Available Abstract Background No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT on pulmonary inflammation or lung function. Methods Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant. Results Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94% were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0ppb, 95%CI: +0.4 to +11.5, and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (−5.9%, 95% CI: -8.9 to −2.9, and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively. Conclusion Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.

  20. Allo-hematopoietic stem cell transplantation is a potential treatment for a patient with a combined disorder of hereditary spherocytosis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; WANG Yu; ZHAO Ting; LIU Kai-yan; HUANG Xiao-jun; FU Hai-xia; XU Lan-ping; LIU Dai-hong; CHEN Huan; HAN Wei; CHEN Yu-hong; WANG Feng-rong; WANG Jing-zhi

    2012-01-01

    Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening.Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation.The complete donor erythroid cells were obtained.The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT).Reticulocyte counts normalized,and BCR-ABL was cleared away.The total bilirubin level was also corrected in this recipient.Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation.HS was not a contraindication for patient in the matched sibling transplant setting.

  1. 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)

    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

  2. Amplitude Variability in gamma Dor and delta Sct Stars Observed by Kepler

    Energy Technology Data Exchange (ETDEWEB)

    Guzik, Joyce Ann [Los Alamos National Laboratory; Kosak, Mary Katherine [Los Alamos National Laboratory; Bradley, Paul Andrew [Los Alamos National Laboratory; Jackiewicz, Jason [New Mexico State University, Las Cruces, NM

    2015-08-17

    The NASA Kepler spacecraft data revealed a large number of new multimode nonradially pulsating gamma Dor and delta Sct variable stars. The Kepler high-precision long time-series photometry makes it possible to study amplitude variations of the frequencies, and recent literature on amplitude and frequency variations in nonradially pulsating variables is summarized. Several methods are applied to study amplitude variability in about a dozen gamma Doradus or delta Scuti candidate variable stars observed for several quarters as part of the Kepler Guest Observer program. The magnitude and timescale of the amplitude variations are discussed, along with the presence or absence of correlations between amplitude variations for different frequencies of a given star. Proposed causes of amplitude spectrum variability that will require further investigation are also discussed.

  3. Iterative local Chi2 alignment approach for the ATLAS SCT detector

    CERN Document Server

    Härtel, Roland

    An approach for the alignment of SCT modules in the ATLAS Inner Detector with particle tracks was developed and implemented in the ATLAS software framework Athena. The approach uses distance of closest approach residuals and a linear least squares minimization to derive the most probable set of alignment parameters for each module. The procedure is iterative, i.e. with the first set of alignment constants a track refit is done and the alignment algorithm is repeated. Correlations between modules are only implicitly taken into account due to the improvement of track parameters through the iterations. A derivation of the underlying concepts is presented. The achievable accuracy and limits of the alignment approach were studied with Monte Carlo simulated tracks in the Athena framework. The results and limitations obtained with the present versions of Athena and the proposed alignment software are presented.

  4. Revisiting The Brightest RV Tauri Star: First Ionization Potential (FIP) Effect in R Sct

    Science.gov (United States)

    Yolalan, Gizay; Sahin, Timur

    2016-07-01

    We have derived elemental abundances of the brightest RV Tauri star, R Sct. The abundance analysis of the star is based on high resolution and high quality (S/N>300) echelle spectra, mainly obtained for radial velocity study of a large sample of IRAS like RV Tau sample stars, from the McDonald Observatory (R~48,000). Our analysis is based on optical spectra obtained at only one phase of the variation. The standard 1D LTE analysis provided a fresh determination of the atmospheric parameters: Teff=5000 K, logg=1.05 cgs, and a microturbulence velocity ξ=3.4 km/s and [Fe/H] = -0.33. We report on chemical abundances of 10 neutral and ionized species identified over 4800 - 5600 A wavelength region. In an effort to explain observed deficiency in abundances, possible scenarios including FIP is investigated.

  5. Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

    International Nuclear Information System (INIS)

    The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain

  6. Serum Krebs Von Den Lungen-6 as a Biomarker for Early Detection of Bronchiolitis Obliterans Syndrome in Children Undergoing Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Gassas, Adam; Schechter, Tal; Krueger, Joerg; Craig-Barnes, Hayley; Sung, Lillian; Ali, Muhammad; Dell, Sharon; Egeler, R Maarten; Zaidman, Irina; Palaniyar, Nades

    2015-08-01

    Bronchiolitis obliterans syndrome (BOS) is a devastating complication after allogeneic stem cell transplantation (allo-SCT). Early identification of high-risk patients is pivotal for success. Lung proteins, KL-6, CCSP, SP-A, and SP-D, measured in the serum may identify high-risk patients for BOS earlier than pulmonary function tests (PFTs) can identify changes or clinical symptoms. Lung proteins were measured in patients' serum at baseline and at 1, 3, 6, 9, 12, 18, and 24 months after transplantation along with history, clinical examination, and PFTs. Serum levels of lung proteins were also measured in healthy control subjects. The primary endpoint was the development of BOS confirmed by pathological biopsy or National Institutes of Health criteria. Between September 2009 and September 2011, 39 patients were enrolled. Six children developed BOS at a median time of 200 days (range, 94 to 282). KL-6 levels were low in control subjects, at a median of .1 U/mL (range, .1 to 1.5). Pre-SCT and 1-month KL-6 levels were significantly higher in surviving patients who developed BOS (n = 6) versus those who did not (n = 18) (pre-SCT: mean, 32.6 U/mL [IQR, 9.7 to 89.3] versus 5.8 U/mL [IQR, 2.1 to 12.6], P = .03; at 1 month: mean, 52.5 U/mL [IQR, 20.2 to 121.3] versus 11.4 U/mL [IQR, 5.7 to 36.0], P = .04). Three- and 6-month KL-6 levels continued to be higher in BOS group but were not statistically significant. CCSP, SP-A, and SP-D were not predictive. KL-6 measured in the serum of children receiving allo-SCT may identify patients at high risk for the development of BOS. These patients will benefit from intensive surveillance protocol and early therapy before irreversible lung damage. PMID:25963919

  7. A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children.

    Science.gov (United States)

    Elbahlawan, Lama; Srinivasan, Ashok; Morrison, R Ray

    2016-04-01

    Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes. PMID:26409244

  8. How do I perform hematopoietic progenitor cell selection?

    Science.gov (United States)

    Avecilla, Scott T; Goss, Cheryl; Bleau, Sharon; Tonon, Jo-Ann; Meagher, Richard C

    2016-05-01

    Graft-versus-host disease remains the most important source of morbidity and mortality associated with allogeneic stem cell transplantation. The implementation of hematopoietic progenitor cell (HPC) selection is employed by some stem cell processing facilities to mitigate this complication. Current cell selection methods include reducing the number of unwanted T cells (negative selection) and/or enriching CD34+ hematopoietic stem/progenitors (positive selection) using immunomagnetic beads subjected to magnetic fields within columns to separate out targeted cells. Unwanted side effects of cell selection as a result of T-cell reduction are primary graft failure, increased infection rates, delayed immune reconstitution, possible disease relapse, and posttransplant lymphoproliferative disease. The Miltenyi CliniMACS cell isolation system is the only device currently approved for clinical use by the Food and Drug Administration. It uses magnetic microbeads conjugated with a high-affinity anti-CD34 monoclonal antibody capable of binding to HPCs in marrow, peripheral blood, or umbilical cord blood products. The system results in significantly improved CD34+ cell recoveries (50%-100%) and consistent 3-log CD3+ T-cell reductions compared to previous generations of CD34+ cell selection procedures. In this article, the CliniMACS procedure is described in greater detail and the authors provide useful insight into modifications of the system. Successful implementation of cell selection procedures can have a significant positive clinical effect by greatly increasing the pool of donors for recipients requiring transplants. However, before a program implements cell selection techniques, it is important to consider the time and financial resources required to properly and safely perform these procedures. PMID:26919388

  9. RESULTS OF HEMATOPOIETIC CELL TRANSPLANTATION IN PEDIATRIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    A. Mousavi

    2008-05-01

    Full Text Available Hematopoietic cell transplantation (HCT is an accepted treatment for acute myeloid leukemia (AML in first remission, the treatment of choice for chronic myeloid leukemia (CML and high risk groups of ALL who relapse with conventional chemotherapy. We assessed results of HCT for pediatric leukemia in our center. A total of 92 children, 63 with diagnose of AML, 23 with ALL and 6 with CML received allogeneic transplantation from HLA full matched siblings (57.6% and autologous transplantation (42.4%. Source of hematopoietic cells were peripheral blood 83.7%, bone marrow 15.2% and cord blood 1.6%. The median transplanted nucleated cells were 6.4 ± 4.7 ×108 /Kg (body weight of patients and mononuclear cells were 5.5 ± 2.9×108/Kg. The most common conditioning regimens were cyclophosphamide + busulfan. Prophylaxis regimen for GVHD was cyclosporin ± methotrexate. GVHD occurred in 50 (54.3% patients. Eighty five of children had engraftment, 26 (28.6% relapsed and 57 (62% are alive. The most common cause of death was relapse (68.6%. Five years overall survival of patients with AML and ALL were 49% and 44% respectively and disease free survival of them were 52% and 49%. One year overall survival and disease free survival of CML was 57%. Overall survival increased with increasing age of patients at transplantation time (P = 0.06. Longer survival significantly related to earlier WBC and platelet recovery (P < 0.0001 and P = 0.006 respectively. Considering acceptable overall and disease free survival of patients after HCT, we concluded that is a good modality in treatment of leukemia of children.

  10. Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients

    Science.gov (United States)

    Tran, Dat; Science, Michelle; Dix, David; Portwine, Carol; Zelcer, Shayna; Johnston, Donna L.; Yanofsky, Rochelle; Gassas, Adam; Ethier, Marie‐Chantal; Sung, Lillian

    2012-01-01

    Please cite this paper as: Tran et al. (2012) Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients. Influenza and Other Respiratory Viruses 6(601), e105–e113. Background  The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes. Methods  We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory‐confirmed pH1N1 infection between May 1, 2009 and January 31, 2010. Results  We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8·7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12·5 days, respectively. 51 (51·5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age 5 days) correlated with shortened duration of viral shedding (P = 0·041). Conclusions  pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices. PMID:22417068

  11. Antibody responses in allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    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

  12. Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant.

    Science.gov (United States)

    Loeffler, Claudia; Kapp, Markus; Grigoleit, Goetz-Ulrich; Mielke, Stephan; Loeffler, Jürgen; Heuschmann, Peter U; Malzahn, Uwe; Hupp, Elke; Einsele, Hermann; Stuhler, Gernot

    2015-01-01

    Allogeneic stem cell transplant is indicated for patients with refractory or relapsed acute myeloid leukemia (AML). Since elimination of the leukemic load is thought to be a prerequisite for treatment success, we here investigate toxicity and anti-leukemic activity of a clofarabine-AraC salvage protocol preceding transplant. In this retrospective analysis, we observed induction of objective remissions in 86% of patients receiving clofarabine-AraC as compared to 83% with sequential high dose AraC/mitoxantrone (S-HAM) and 50% after mitoxantrone/topotecane/AraC (MTC) salvage strategies. In addition, clofarabine conferred anti-leukemic activity to some patients who failed initial MTC or S-HAM therapy. For overall and leukemia-free survival, we identified cytogenetically defined adverse risk markers but not response to therapy to be a strong predictor. In summary, the clofarabine-AraC salvage strategy combines pronounced anti-leukemic activity with an acceptable toxicity profile and allows the majority of patients with relapsed or refractory AML to proceed to allo-SCT, even in cytogenetically defined high risk situations. PMID:26014275

  13. Risk Factors and Impact of Secondary Failure of Platelet Recovery After Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Akahoshi, Yu; Kanda, Junya; Gomyo, Ayumi; Hayakawa, Jin; Komiya, Yusuke; 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; Kanda, Yoshinobu

    2016-09-01

    Secondary failure of platelet recovery (SFPR), a late decrease in the platelet count after primary platelet recovery that is not due to relapse or graft rejection, occasionally occurs after allogeneic hematopoietic stem cell transplantation (HSCT). The risk factors and impact of SFPR on transplantation outcomes are not well known in the clinical setting. Therefore, we retrospectively evaluated 184 adult patients who underwent their first allogeneic HSCT and achieved primary platelet recovery. The cumulative incidence of SFPR, defined as a decrease in the platelet count to below 20,000/µL for more than 7 days, was 12.2% at 3 years, with a median onset of 81 days (range, 39 to 729) after HSCT. Among patients who developed SFPR (n = 23), 19 (82.6%) showed recovery to a sustained platelet count of more than 20,000/µL without transfusion support, and the median duration of SFPR was 23 days (range, 7 to 1048 days). A multivariate analysis showed that in vivo T cell depletion (hazard ratio [HR], 6.92; 95% confidence interval [CI], 2.31 to 20.7; P < .001), grades II to IV acute graft-versus-host disease (HR, 3.99; 95% CI, 1.52 to 10.5; P = .005), and the use of ganciclovir or valganciclovir (HR, 2.86; 95% CI, 1.05 to 7.77; P = .039) were associated with an increased risk for SFPR. The occurrence of SFPR as a time-dependent covariate was significantly associated with inferior overall survival (HR, 2.29; 95% CI, 1.18 to 4.46; P = .015) in a multivariate analysis. These findings may help to improve the management and treatment strategy for SFPR. PMID:27288954

  14. 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. PMID:27246369

  15. HEMATOPOIETIC CELL TRANSPLANTATION FOR OLDER PATIENTS WITH MDS

    Directory of Open Access Journals (Sweden)

    Mazyar Shadman

    2014-09-01

    Full Text Available The incidence of myeloid malignancies, including myelodysplastic syndromes (MDS increases with age. While several therapeutic modalities have been developed, for most of these patients the only treatment with curative potential is allogeneic hematopoietic cell transplantation (HCT. The development of reduced/low intensity transplant conditioning regimens allows to successfully transplant patients in their ‘60s and even ‘70s, although comorbidities may determine who does come to transplantation and who does not. Also, as many as half of the patients will develop graft versus host disease (GVHD, even with HLA matched  donors, requiring therapy for extended periods of time,  and GVHD and treatment  with glucocorticoids is likely to impact the quality  of life. Nevertheless, dependent upon disease stage at HCT, the presence of comorbidities and the regimen used, 30% to 50% of patients  60 years of age or older, may survive long-term cured of their disease. Future studies should focus on the incorporation of non-transplant modalities into the overall transplant approach, the prevention of GVHD, and the utilization of immunotherapy to reduce the incidence of relapse and GVHD and further improve overall transplant success.

  16. Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

    Science.gov (United States)

    Gagne, K; Loiseau, P; Dubois, V; Dufossé, F; Perrier, P; Dormoy, A; Jollet, I; Renac, V; Masson, D; Picard, C; Lafarge, X; Hanau, D; Quainon, F; Delbos, F; Coeffic, B; Absi, Léna; Eliaou, J-F; Moalic, V; Fort, M; de Matteis, M; Theodorou, I; Hau, F; Batho, A; Pedron, B; Caillat-Zucman, S; Marry, E; Raus, N; Yakoub-Agha, I; Cesbron, A

    2015-02-01

    We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT. PMID:25365066

  17. Electrical test results from ATLAS-SCT end-cap modules

    CERN Document Server

    Mangin-Brinet, M; Donega, M; D'Onofrio, M; Ferrère, D; Mikulec, B; Moed, S; Weber, M; Hartjes, F; Muijs, S; Peeters, S; Chouridou, S; Roe, S; Wallny, R; Bernabeu, J; Lacasta, C; Feld, L; Ketterer, C; Meinhardt, J; Dolezal, Z; Kodys, P; Kubik, P; Reznicek, P; Allport, P P; Dervan, P J; Greenall, A; Jackson, J N; Jones, T J; Phillips, P W; Smith, N A; Sutcliffe, P; Tavera, M

    2003-01-01

    The LHC operating conditions present several challenges to the module performance of the ATLAS Semiconductor Tracker (SCT). This detector consists of four cylindrical barrel layers of silicon strip detectors and of 18 disks in the forward and backward direction. Four different module designs exist, one for the barrel and three (inner, middle and outer) for the rings of the disks. A series of several end-cap module pre-production prototypes of inner, middle and outer types have been built and extensively characterized on single module test benches in the institutes of the collaboration. The scope of this document is to summarize the electrical performance measurements made in laboratory on these end-cap module pre-production prototypes, with special emphasis on the result of electrical tests after irradiation. As summarized in the conclusion, the electrical performance specifications are met before irradiation, but are exceeded after an irradiation dose of $1.5.10^{14}$p/cm$^2$, that is a fluence corresponding...

  18. Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero.

    Science.gov (United States)

    Ihara, Norimasa; Akihiro, Umezawa; Onami, Naoko; Tsumura, Hideki; Inoue, Eisuke; Hayashi, Satoshi; Sago, Haruhiko; Mizutani, Shuki

    2015-02-01

    In utero hematopoietic cell transplantation (IUHCT) has been performed in Mucopolysaccharidosis Type VII (MPSVII) mice, but a lifelong engraftment of allogeneic donor cells has not been achieved. In this study, we sought to confirm a lifelong engraftment of allogeneic donor cells immunologically matched to the mother and to achieve partial rescue of phenotypes in the original MPSVII strain through IUHCT by intravenous injection. We performed in vitro fertilization in a MPSVII murine model and transferred affected embryos to ICR/B6-GFP surrogate mothers in cases where fetuses receiving IUHCT were all homozygous. Lineage-depleted cells from ICR/B6-GFP mice were injected intravenously at E14.5. Chimerism was confirmed by flow cytometry at 4 weeks after birth, and β-glucuronidase activity in serum and several phenotypes were assessed at 8 weeks of age or later. Donor cells in chimeric mice from ICR/B6-GFP mothers were detected at death, and were confirmed in several tissues including the brains of sacrificed chimeric mice. Although the serum enzyme activity of chimeric mice was extremely low, the engraftment rate of donor cells correlated with enzyme activity. Furthermore, improvement of bone structure and rescue of reproductive ability were confirmed in our limited preclinical study. We confirmed the lifelong engraftment of donor cells in an original immunocompetent MPSVII murine model using intravenous IUHCT with cells immunologically matched to the mother without myeloablation, and the improvement of several phenotypes. PMID:25421592

  19. Construction of an allogenic chimeric mouse model for the study of the behaviors of donor stem cells in vivo

    Institute of Scientific and Technical Information of China (English)

    WANG Mo-lin; YAN Jing-bin; XIAO Yan-ping; HUANG Shu-zhen

    2005-01-01

    Background It is essential to establish an animal model for the elucidation of the biological behaviors of stem cells in vivo. We constructed a chimeric animal model by in utero transplantation for investigation of stem cell transplantation.Methods This chimerism was achieved by injecting the stem cells derived from the bone marrow of green fluorescence protein (GFP)-transgenic mice into fetal mice at 13.5 days of gestation. Several methods such as polymerase chain reaction (PCR), real-time PCR, fluorescence-assisted cell sorting (FACS) and fluorescence in situ hybridization (FISH) were used for the observation of donor cells.Results Under a fluorescence microscope, we observed the GFP cells of donor-origin in a recipient. PCR, FACS analysis and FISH indicated chimerism at various intervals. Real-time PCR indicated that some donor cells existed in chimera for more than 6 months.Conclusions Allogenic stem cells may exist in recipients for a long time and this allogenic animal model provides a useful tool for studying the behavior of hematopoietic stem cells and also offers an effective model system for the study of stem cells.

  20. Relationship between neurocognitive functioning and medication management ability over the first 6 months following allogeneic stem cell transplantation.

    Science.gov (United States)

    Mayo, S; Messner, H A; Rourke, S B; Howell, D; Victor, J C; Kuruvilla, J; Lipton, J H; Gupta, V; Kim, D D; Piescic, C; Breen, D; Lambie, A; Loach, D; Michelis, F V; Alam, N; Uhm, J; McGillis, L; Metcalfe, K

    2016-06-01

    Although neurocognitive impairment has been established as a major issue among cancer survivors, the real-world consequences of this impairment are unclear. This study investigated the relationship between neurocognitive functioning and medication management ability over time among 58 patients treated with allogeneic hematopoietic stem cell transplantation (HCT). Participants completed a neuropsychological test battery and a simulated medication management task at three time points: pre-transplant (T0), Day 100 (T1) and 6 months post transplant (T2). Neurocognitively impaired participants performed worse on the medication management task than neurocognitively normal participants at each time point, and were more likely to score in the impaired range of medication management ability post transplant (72% vs 20%, Pperformance in executive functioning/working memory consistently predicted impaired medication management ability, even when controlling for sociodemographic and clinical confounders (odds ratio=0.89, 95% confidence interval (0.80, 0.98), P=0.023). Lower physical symptom distress also predicted impaired medication management ability, but this effect decreased over time. Self-reported cognitive problems were not correlated with medication management ability at any time point. Findings suggest that poor neurocognitive functioning, particularly in the domain of executive functioning/working memory, is associated with worse medication management ability within the first 6 months after allogeneic HCT. PMID:26926230

  1. Clostridium difficile infection in Chilean patients submitted to hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Javier Pilcante

    2015-12-01

    Full Text Available ABSTRACT Introduction: Patients submitted to hematopoietic stem cell transplantation have an increased risk of Clostridium difficile infection and multiple risk factors have been identi- fied. Published reports have indicated an incidence from 9% to 30% of transplant patients however to date there is no information about infection in these patients in Chile. Methods: A retrospective analysis was performed of patients who developed C. difficile infection after hematopoietic stem cell transplantations from 2000 to 2013. Statistical analysis used the Statistical Package for the Social Sciences software. Results: Two hundred and fifty patients were studied (mean age: 39 years; range: 17-69, with 147 (59% receiving allogeneic transplants and 103 (41% receiving autologous trans- plants. One hundred and ninety-two (77% patients had diarrhea, with 25 (10% cases of C. difficile infection being confirmed. Twenty infected patients had undergone allogeneic trans- plants, of which ten had acute lymphoblastic leukemia, three had acute myeloid leukemia and seven had other diseases (myelodysplastic syndrome, chronic myeloid leukemia, severe aplastic anemia. In the autologous transplant group, five patients had C. difficile infection; two had multiple myeloma, one had amyloidosis, one had acute myeloid leukemia and one had germinal carcinoma. The overall incidence of C. difficile infection was 4% within the first week, 6.4% in the first month and 10% in one year, with no difference in overall survival between infected and non-infected groups (72.0% vs. 67.6%, respectively; p-value = 0.56. Patients infected after allogeneic transplants had a slower time to neutrophil engraftment compared to non-infected patients (17.5 vs. 14.9 days, respectively; p-value = 0.008. In the autologous transplant group there was no significant difference in the neutrophil engraftment time between infected and non-infected patients (12.5 days vs. 11.8 days, respectively; p

  2. HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

    Directory of Open Access Journals (Sweden)

    Andrea Pession

    2011-06-01

    Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

  3. Successful Hematopoietic Stem Cell Transplantation Following a Cyclophosphamide-Containing Preparative Regimen with Concomitant Phenobarbital Administration

    Directory of Open Access Journals (Sweden)

    Catherine Weber

    2012-01-01

    Full Text Available Cyclophosphamide is an immunosuppressive agent and an anticancer prodrug which requires bioactivation catalyzed primarily by cytochrome P450 enzymes in order to be transformed into its active alkylating compounds. Concomitant administration of drugs known to inhibit or induce this enzyme system is a clinical concern. Herein, we present the case of a chronically ill 21-year-old patient who received high-dose cyclophosphamide, equine antithymocyte globulin (eATG, and total body irradiation (TBI followed by an allogeneic hematopoietic stem cell transplant (HSCT for severe aplastic anemia. Throughout her hospitalization, she continued to receive quadruple anticonvulsant therapy including phenobarbital for her long-standing seizure history. The preparative regimen was tolerated well aside from a hypersensitivity reaction to eATG, and minimal cyclophosphamide-related toxicities. Safe and effective administration of high-dose cyclophosphamide was possible with multidisciplinary care consisting of physician, nursing, pharmacy, neurology consultation, as well as social work and case management.

  4. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

    Science.gov (United States)

    Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

    2016-06-01

    Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation. PMID:26901703

  5. UNRELATED DONOR ALLOGENEIC TRANSPLANTATION AFTER FAILURE OF AUTOLOGOUS TRANSPLANTATION FOR ACUTE MYELOID LEUKEMIA: A STUDY FROM THE CIBMTR

    Science.gov (United States)

    Foran, James M.; Pavletic, Steven Z.; Logan, Brent R.; Agovi-Johnson, Manza A.; Pérez, Waleska S.; Bolwell, Brian J.; Bornhäuser, Martin; Bredeson, Christopher N.; Cairo, Mitchell S.; Camitta, Bruce M.; Copelan, Edward A.; Dehn, Jason; Gale, Robert P.; George, Biju; Gupta, Vikas; Hale, Gregory A.; Lazarus, Hillard M.; Litzow, Mark R.; Maharaj, Dipnarine; Marks, David I.; Martino, Rodrigo; Maziarz, Richard T.; Rowe, Jacob M.; Rowlings, Philip A.; Savani, Bipin N.; Savoie, Mary Lynn; Szer, Jeffrey; Waller, Edmund K.; Wiernik, Peter H.; Weisdorf, Daniel J.

    2013-01-01

    The survival of relapsed acute myeloid leukemia (AML) after autologous hematopoietic stem cell transplantation (Autologous HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (Allo-HCT) from an unrelated donor (URD) using either myeloablative (n=242) or reduced-intensity conditioning regimens (RIC, n=60) reported to CIBMTR. After a median follow-up of 58 months (range 2–160), the probability of treatment-related mortality (TRM) was 44% (95%CI 38–50) at 1-year. The 5-year incidence of relapse and overall survival (OS) was 32% (95%CI 27–38) and 22% (95%CI 18–27), respectively. In multivariate analysis significantly better OS was observed with RIC regimens (Hazard Ratio (HR) 0.51, 95%CI 0.35–0.75, p18 months) from Autologous HCT to URD Allo-HCT was associated with significantly lower Relapse risk (HR 0.19, 95%CI 0.09–0.38, p<0.001) and improved LFS (HR 0.53, 95%CI 0.34–0.84, p=0.006). URD Allo-HCT after Autologous HCT relapse results in 20% long-term leukemia-free survival, with best results with longer interval to secondary URD transplantation, KPS ≥90%, in complete remission, and using RIC regimens. Further efforts to reduce TRM and relapse are still needed. PMID:23632091

  6. Tuberculosis in hematopoietic stem cell transplant patients: case report and review of the literature.

    Science.gov (United States)

    Russo, Rachel Leite; Dulley, Frederico Luiz; Suganuma, Liliana; França, Ivan Leonardo; Yasuda, Maria Aparecida Shikanai; Costa, Silvia Figueiredo

    2010-09-01

    The literature describing tuberculosis (TB) in hematopoietic stem cell transplant (HSCT) recipients is scant, even in countries where TB is common. We describe a case of pulmonary TB in a patient who underwent HSCT and review the English language literature on this subject. An extensive PubMed and Ovid search was undertaken for the period January 1980 to March 2009; the search terms used were 'Mycobacterium tuberculosis' or 'tuberculosis', in combination with 'hematopoietic stem cell transplantation' or 'bone marrow transplantation'. The patient in the present case report underwent allogeneic transplantation and developed TB 8 days after his HSCT. The patient had received vaccination against TB in childhood. During the year prior to the HSCT he had had contact with a relative who had pulmonary TB. On day 3 of anti-TB treatment he developed pericarditis. The patient received anti-TB treatment for 6 months without major problems. From the literature review, we found 34 related studies, 25 on the clinical manifestations of TB. Most of the reports were from Asia (48%), and the incidence of TB varied from 0.0014% in the USA to 16% in Pakistan. TB occurred at between +21 and +1410 days post-HSCT (257.2 days the median), and the lung was the organ most frequently involved. Mortality varied from 0% to 50% and was higher in allogeneic HSCT. There is no consensus regarding screening with the tuberculin skin test or primary prophylaxis for latent TB, and further research into this is necessary in developing countries with a high prevalence of TB. PMID:19819176

  7. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

    International Nuclear Information System (INIS)

    Background and purpose: To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT). Materials and Methods: Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease. Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.

  8. Histocompatibility and Hematopoietic Transplantation in the Zebrafish

    Directory of Open Access Journals (Sweden)

    Jill L. O. de Jong

    2012-01-01

    Full Text Available The zebrafish has proven to be an excellent model for human disease, particularly hematopoietic diseases, since these fish make similar types of blood cells as humans and other mammals. The genetic program that regulates the development and differentiation of hematopoietic cells is highly conserved. Hematopoietic stem cells (HSCs are the source of all the blood cells needed by an organism during its lifetime. Identifying an HSC requires a functional assay, namely, a transplantation assay consisting of multilineage engraftment of a recipient and subsequent serial transplant recipients. In the past decade, several types of hematopoietic transplant assays have been developed in the zebrafish. An understanding of the major histocompatibility complex (MHC genes in the zebrafish has lagged behind transplantation experiments, limiting the ability to perform unbiased competitive transplantation assays. This paper summarizes the different hematopoietic transplantation experiments performed in the zebrafish, both with and without immunologic matching, and discusses future directions for this powerful experimental model of human blood diseases.

  9. Alternative-Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Nonmalignant Disorders.

    Science.gov (United States)

    Klein, Orly R; Chen, Allen R; Gamper, Christopher; Loeb, David; Zambidis, Elias; Llosa, Nicolas; Huo, Jeffrey; Dezern, Amy E; Steppan, Diana; Robey, Nancy; Holuba, Mary Jo; Cooke, Kenneth R; Symons, Heather J

    2016-05-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA-matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life-threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted. PMID:26860634

  10. Significance of a positive Clostridium difficile toxin test after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Akahoshi, Yu; Kimura, Shun-Ichi; Nakano, Hirofumi; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Nakasone, Hideki; Kikuchi, Misato; Yamazaki, Rie; Kanda, Junya; Kako, Shinichi; Nishida, Junji; Kanda, Yoshinobu

    2016-06-01

    Patients with hematological malignancies show a high prevalence of asymptomatic colonization with Clostridium difficile (CD colonization). Therefore, it is difficult to distinguish CD colonization with diarrhea induced by a conditioning regimen from true Clostridium difficile infection (CDI) in hematopoietic stem cell transplantation (HSCT) recipients. We retrospectively analyzed 308 consecutive patients who underwent a CD toxin A/B enzyme immunoassay test for diarrhea within 100 d after HSCT from November 2007 to May 2014. Thirty patients (9.7%) had positive CD toxin results, and 11 of these had positive results in subsequent tests after an initial negative result. Allogeneic HSCT, total body irradiation, stem cell source, acute leukemia, and the duration of neutropenia were significantly correlated with positive CD toxin results. In a logistic regression model, allogeneic HSCT was identified as a significant risk factor (odds ratio 18.6, p < 0.01). In an analysis limited to within 30 d after the conditioning regimen, the duration of neutropenia was the sole risk factor (odds ratio 10.4, p < 0.01). There were no distinctive clinical features for CDI, including the onset or duration of diarrhea. In conclusion, although CDI may be overdiagnosed in HSCT recipients, it is difficult to clinically distinguish between CDI and CD colonization. PMID:27019071

  11. Enhancing T cell reconstitution after hematopoietic stem cell transplantation: a brief update of the latest trends

    Science.gov (United States)

    Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Smith, Odette M.; van den Brink, Marcel R.M.

    2009-01-01

    Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway. PMID:17905611

  12. A prognostic index for survival among mechanically ventilated hematopoietic cell transplant recipients.

    Science.gov (United States)

    Solh, Melhem; Oommen, Sanjay; Vogel, Rachel Isaksson; Shanley, Ryan; Majhail, Navneet S; Burns, Linda J

    2012-09-01

    The prognosis of recipients of allogeneic hematopoietic cell transplantation (HCT) who require mechanical ventilation (MV) has historically been poor. Of 883 adults undergoing allogeneic HCT at the University of Minnesota between 1998 and 2009, 179 (20%) required MV before day 100 posttransplantation. We evaluated the outcomes of these patients to develop a prognostic index to predict the 100-day post-MV overall survival (OS) based on factors present at the time of MV. The 179 patients were divided at random into a training set (n = 119) and a validation set (n = 60). The 100-day postventilation OS was 17% for the total population. Multivariate Cox regression on the training set identified creatinine 20 × 10(9)/L as significant predictors of better OS. Recursive partitioning classified patients with these good prognostic criteria into class A (n = 76); all other patients were classified as class B (n = 103). Among class A patients, 100-day OS was 29% in the training set and 30% in the validation set. Corresponding OS in class B patients was 5% and 15%, respectively. This prognostic index should help guide physicians in counseling HCT patients and their families regarding the use of MV and potential outcomes. PMID:22387348

  13. Acute megakaryoblastic leukemia, unlike acute erythroid leukemia, predicts an unfavorable outcome after allogeneic HSCT.

    Science.gov (United States)

    Ishiyama, Ken; Yamaguchi, Takuhiro; Eto, Tetsuya; Ohashi, Kazuteru; Uchida, Naoyuki; Kanamori, Heiwa; Fukuda, Takahiro; Miyamura, Koichi; Inoue, Yoshiko; Taguchi, Jun; Mori, Takehiko; Iwato, Koji; Morishima, Yasuo; Nagamura-Inoue, Tokiko; Atsuta, Yoshiko; Sakamaki, Hisashi; Takami, Akiyoshi

    2016-08-01

    Acute erythroid leukemia (FAB-M6) and acute megakaryoblastic leukemia (FAB-M7) exhibit closely related properties in cells regarding morphology and the gene expression profile. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered the mainstay of the treatment for both subtypes of leukemia due to their refractoriness to chemotherapy and high rates of relapse, it remains unclear whether allo-HSCT is curative in such cases due to their scarcity. We retrospectively examined the impact of allo-HSCT in 382 patients with M6 and 108 patients with M7 using nationwide HSCT data and found the overall survival (OS) and relapse rates of the M6 patients to be significantly better than those of the M7 patients after adjusting for confounding factors and statistically comparable with those of the patients with M0/M1/M2/M4/M5 disease. Consequently, the factors of age, gender, performance status, karyotype, disease status at HSCT and development of graft-vs.-host disease predicted the OS for the M6 patients, while the performance status and disease status at HSCT were predictive of the OS for the M7 patients. These findings substantiate the importance of distinguishing between M6 and M7 in the HSCT setting and suggest that unknown mechanisms influence the HSCT outcomes of these closely related subtypes of leukemia. PMID:27244257

  14. MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation.

    Science.gov (United States)

    Tomuleasa, Ciprian; Fuji, Shigeo; Cucuianu, Andrei; Kapp, Markus; Pileczki, Valentina; Petrushev, Bobe; Selicean, Sonia; Tanase, Alina; Dima, Delia; Berindan-Neagoe, Ioana; Irimie, Alexandru; Einsele, Hermann

    2015-07-01

    Allogeneic hematopoietic stem cell transplantation (HCT) is a well-established treatment for many malignant and non-malignant hematological disorders. As frequent complication in up to 50 % of all patients, graft-versus-host disease (GVHD) is still the main cause for morbidity and non-relapse mortality. Diagnosis of GVHD is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally recognized consensus has yet been established. Here, microRNAs (miRs) represent an interesting tool since miRs have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we could assume that miRs play a key role in the pathogenesis of acute GVHD, and their detection might be an interesting possibility in the early diagnosis and monitoring of acute GVHD. Recent studies additionally demonstrated the implication of miRs in the pathogenesis of acute GVHD. In this review, we aim to summarize the previous reports of miRs, focusing on the pathogenesis of acute GVHD and possible implications in diagnostic approaches. PMID:25900787

  15. 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 (<24 months) to intensive treatments, and/or presence of 17p/TP53 abnormalities). Currently, new and highly effective therapeutic agents targeting BCR-mediated intracellular signal transduction have been incorporated into the 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. PMID:25651976

  16. Use of the quality management system "JACIE" and outcome after hematopoietic stem cell transplantation.

    Science.gov (United States)

    Gratwohl, Alois; Brand, Ronald; McGrath, Eoin; van Biezen, Anja; Sureda, Anna; Ljungman, Per; Baldomero, Helen; Chabannon, Christian; Apperley, Jane

    2014-05-01

    Competent authorities, healthcare payers and hospitals devote increasing resources to quality management systems but scientific analyses searching for an impact of these systems on clinical outcome remain scarce. Earlier data indicated a stepwise improvement in outcome after allogeneic hematopoietic stem cell transplantation with each phase of the accreditation process for the quality management system "JACIE". We therefore tested the hypothesis that working towards and achieving "JACIE" accreditation would accelerate improvement in outcome over calendar time. Overall mortality of the entire cohort of 107,904 patients who had a transplant (41,623 allogeneic, 39%; 66,281 autologous, 61%) between 1999 and 2006 decreased over the 14-year observation period by a factor of 0.63 per 10 years (hazard ratio: 0.63; 0.58-0.69). Considering "JACIE"-accredited centers as those with programs having achieved accreditation by November 2012, at the latest, this improvement was significantly faster in "JACIE"-accredited centers than in non-accredited centers (approximately 5.3% per year for 49,459 patients versus approximately 3.5% per year for 58,445 patients, respectively; hazard ratio: 0.83; 0.71-0.97). As a result, relapse-free survival (hazard ratio 0.85; 0.75-0.95) and overall survival (hazard ratio 0.86; 0.76-0.98) were significantly higher at 72 months for those patients transplanted in the 162 "JACIE"-accredited centers. No significant effects were observed after autologous transplants (hazard ratio 1.06; 0.99-1.13). Hence, working towards implementation of a quality management system triggers a dynamic process associated with a steeper reduction in mortality over the years and a significantly improved survival after allogeneic stem cell transplantation. Our data support the use of a quality management system for complex medical procedures. PMID:24488562

  17. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  18. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  19. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Alois Gratwohl

    2015-12-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37% or autologous (N = 65,007; 63% HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84–0·91 per 10 patients; p < 0·0001; HR 0·90;0·85–0·90 per 10 years; p < 0·001 and autologous HSCT (HR 0·91;0·87–0·96 per 10 patients; p < 0·001; HR 0·93;0·87–0·99 per 10 years; p = 0·02. The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R2 = 18%; for relapse free survival after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments.

  20. Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study.

    Science.gov (United States)

    Gratwohl, Alois; Sureda, Anna; Baldomero, Helen; Gratwohl, Michael; Dreger, Peter; Kröger, Nicolaus; Ljungman, Per; McGrath, Eoin; Mohty, Mohamad; Nagler, Arnon; Rambaldi, Alessandro; de Elvira, Carmen Ruiz; Snowden, John A; Passweg, Jakob; Apperley, Jane; Niederwieser, Dietger; Stijnen, Theo; Brand, Ronald

    2015-12-01

    Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country-specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0·87; 0·84-0·91 per 10 patients; p < 0·0001; HR 0·90;0·85-0·90 per 10 years; p < 0·001) and autologous HSCT (HR 0·91;0·87-0·96 per 10 patients; p < 0·001; HR 0·93;0·87-0·99 per 10 years; p = 0·02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments. PMID:26844291

  1. Poor concordance of spiral CT (SCT) and high probability ventilation-perfusion (V/Q) studies in the diagnosis of pulmonary embolism (PE)

    International Nuclear Information System (INIS)

    Full text: Despite its limitations, V/Q scintigraphy remains the favoured non-invasive technique for the diagnosis of pulmonary embolism (PE). PE is present in 85-90% and 30-40% of high and intermediate probability V/Q studies respectively. The value of spiral CT (SCT), a newer imaging modality, has yet to be determined. The aims of this study were to determine the frequency of positive SCT for PE in high and intermediate probability V/Q studies performed within 24hr apart. 15 patients (6M, 9F, mean age - 70.2) with a high probability study were included. Six (40%) SCT were reported as positive (four with emboli present in the main pulmonary arteries), seven as negative, one equivocal and one was technically sub-optimal. Pulmonary angiography was not performed in any patient. In all seven negative studies, the SCT was performed before the V/Q study. Of these, two studies were revised to positive once the result of the V/Q study was known, while, three others had resolving mismatch V/Q defects on follow-up studies (performed 5-14 days later); two of these three also had a positive duplex scan of the lower limbs. One other was most likely due to chronic thromboembolic disease. Only three patients had a V/Q scan prior to the SCT; all were positive for PE on both imaging modalities. Of 26 patients (11M, 15F, mean age - 68.5) with an intermediate probability V/Q study, SCT was positive in only two (8%). Thus the low detection rate of PE by SCT in this albeit small series, raises doubts as to its role in the diagnosis of PE. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  2. Unrelated donors are associated with improved relapse-free survival compared to related donors in patients with myelodysplastic syndrome undergoing reduced intensity allogeneic stem cell transplantation.

    Science.gov (United States)

    Yam, Clinton; Crisalli, Lisa; Luger, Selina M; Loren, Alison W; Hexner, Elizabeth O; Frey, Noelle V; Mangan, James K; Gao, Amy; Stadtmauer, Edward A; Porter, David L; Reshef, Ran

    2016-09-01

    Reduced intensity allogeneic stem cell transplantation (RI alloSCT) is a potentially curative treatment approach for patients with myelodysplastic syndrome (MDS). It is currently unclear if older related donors are better than younger unrelated donors for patients with MDS undergoing RI alloSCT. We retrospectively studied 53 consecutive MDS patients who underwent RI alloSCT between April 2007 and June 2014 and evaluated associations between donor type and outcomes with adjustment for significant covariates. 34 patients (median age: 64 years) and 19 patients (median age: 60 years) received allografts from unrelated and related donors, respectively. Unrelated donors were younger than related donors (median age: 32 vs. 60 years, P < 0.0001). There were no significant differences in baseline disease characteristics of patients receiving allografts from related or unrelated donors. Patients who received allografts from unrelated donors had a lower relapse risk (adjusted hazard ratio [aHR] = 0.35, P = 0.012) and improved relapse-free survival (aHR = 0.47, P = 0.018). HLA mismatched unrelated donors were associated with a higher risk of grade 2-4 acute graft versus host disease (GVHD) (HR = 4.64, P = 0.002) without an accompanying increase in the risk of non-relapse mortality (P = 0.56). Unrelated donors provided a higher mean CD8 cell dose (P = 0.014) and were associated with higher median donor T cell chimerism at day 60 (P = 0.003) and day 100 (P = 0.03). In conclusion, patients with MDS who received allografts from unrelated donors had a lower risk of relapse and improved relapse-free survival when compared to patients who received allografts from related donors. These findings should be confirmed in a prospective study. Am. J. Hematol. 91:883-887, 2016. © 2016 Wiley Periodicals, Inc. PMID:27197602

  3. Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic stem cell transplantation in patients with multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-hui; LU Dao-pei; HUANG Xiao-jun; LIU Kai-yan; XU Lan-ping; LIU Dai-hong; CHEN Huan; CHEN Yu-hong; WANG Jing-zhi; HAN Wei

    2007-01-01

    Background Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma.The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.Methods The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine.Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day -10 and cytarabine (2 g/m2) was given on day -9, busulfan was administered orally in four divided doses daily for 3 days (days -8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1hour on days -5 and -4 (1.8 g/m2), and with semustine (Me-CCNU) 250 mg/m2 on day -3.Results Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI:13.9%-38.6%). Two patients (18.2%) developed grade Ⅰ acute GVHD (95% CI:10.9%-35.9%) and grade Ⅱ acute GVHD occurred in one patient (9.1%;95% CI: 8.4%-32.3%). Severe grade Iva GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7%-36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3%-34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3%-46.7%). The estimated 4-year

  4. The role of the embryonic microenvironment in hematopoietic cell development

    NARCIS (Netherlands)

    E. Haak (Esther)

    2007-01-01

    textabstractThe adult hematopoietic system is comprised of a hierarchy of cells with the hematopoietic stem cell (HSC) at its foundation. HSCs give rise to progenitors that differentiate into mature hematopoietic cells, which perform the physiological functions of the hematopoietic system. The matur

  5. Differential Effect of MyD88 Signal in Donor T Cells on Graft-versus-Leukemia Effect and Graft-versus-Host Disease after Experimental Allogeneic Stem Cell Transplantation.

    Science.gov (United States)

    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Choi, Eun Young; Min, Chang-Ki

    2015-11-01

    Despite the presence of toll like receptor (TLR) expression in conventional TCRαβ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 (H-2(b)) → B6D2F1 (H-2(b/d)), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type (H-2(d)) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-γ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-γ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT. PMID:26552489

  6. Tetanus after allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    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.)

  7. Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation.

    Science.gov (United States)

    Broxmeyer, Hal E

    2016-06-01

    Clinical cord blood (CB) hematopoietic cell transplantation (HCT) has progressed well since the initial successful CB HCT that saved the life of a young boy with Fanconi anemia. The recipient is alive and well now 28 years out since that first transplant with CB cells from his HLA-matched sister. CB HCT has now been used to treat over 35,000 patients with various malignant and non-malignant disorders mainly using HLA-matched or partially HLA-disparate allogeneic CB cells. There are advantages and disadvantages to using CB for HCT compared to other sources of transplantable hematopoietic stem (HSC) and progenitor (HPC) cells. One disadvantage of the use of CB as a source of transplantable HSC and HPC is the limited number of these cells in a single CB collected, and slower time to neutrophil, platelet and immune cell recovery. This review describes current attempts to: increase the collection of HSC/HPC from CB, enhance the homing of the infused cells, ex-vivo expand numbers of collected HSC/HPC and increase production of the infused CB cells that reach the marrow. The ultimate goal is to manipulate efficiency and efficacy for safe and economical use of single unit CB HCT. PMID:27211041

  8. Molecular mechanisms underlying adhesion and migration of hematopoietic stem cells

    OpenAIRE

    Sahin, Aysegul Ocal; Buitenhuis, Miranda

    2012-01-01

    Hematopoietic stem cell transplantation is the most powerful treatment modality for a large number of hematopoietic malignancies, including leukemia. Successful hematopoietic recovery after transplantation depends on homing of hematopoietic stem cells to the bone marrow and subsequent lodging of those cells in specific niches in the bone marrow. Migration of hematopoietic stem cells to the bone marrow is a highly regulated process that requires correct regulation of the expression and activit...

  9. Generation of axolotl hematopoietic chimeras

    Directory of Open Access Journals (Sweden)

    David Lopez

    2015-02-01

    Full Text Available Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells.  Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration.  Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing.  Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration.  Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration.

  10. Allogeneic split-skin grafting in stem cell transplanted patients

    DEFF Research Database (Denmark)

    Olsen, Jan Kyrre Berg; Vindeløv, Lars; Schmidt, G.;

    2008-01-01

    SUMMARY: We present a unique case of a bone marrow stem cell transplanted (BMT) patient with cutaneous chronic Graft versus Host Disease (cGvHD) who underwent successful allogeneic split-thickness skin graft (STSG) transplantation. BMT had previously been carried out due to myelodysplasia and non......). Allogeneic skin grafts are known to be acutely rejected. Successful allogeneic STSG has only been reported in sporadic cases of identical twins (isotransplantation). This case is the first to demonstrate what works in theory: the immune system of a stem cell transplanted patient with 100% or mixed stable...... donor chimaerism will not recognise skin from the stem cell donor as foreign. Due to advances in haematology, the number of BMT patients and their long-term survival is expected to increase. cGvHD, predisposing to skin problems and ulcerations, complicates up to 70% of cases of BMT. In BMT patients...

  11. Radiation hardness and lifetime studies of LEDs and VCSELs for the optical readout of the ATLAS SCT

    CERN Document Server

    Beringer, J; Mommsen, R K; Nickerson, R B; Weidberg, A R; Monnier, E; Hou, H Q; Lear, K L

    1999-01-01

    We study the radiation hardness and the lifetime of Light Emitting Diodes (LEDs) and Vertical Cavity Surface Emitting Laser diodes (VCSELs) in the context of the development of the optical readout for the ATLAS SemiConductor Tracker (SCT) at LHC. About 170 LEDs from two different manufacturers and about 130 VCSELs were irradiated with neutron and proton fluences equivalent to (and in some cases more than twice as high as) the combined neutral and charged particle fluence of about 5x10 sup 1 sup 4 n (1 MeV eq. in GaAs)/cm sup 2 expected in the ATLAS inner detector. We report on the radiation damage and the conditions required for its partial annealing under forward bias, we calculate radiation damage constants, and we present post-irradiation failure rates for LEDs and VCSELs. The lifetime after irradiation was investigated by operating the diodes at an elevated temperature of 50 degree sign C for several months, resulting in operating times corresponding to up to 70 years of operation in the ATLAS SCT. From o...

  12. Return to the hematopoietic stem cell origin

    OpenAIRE

    Samokhvalov, Igor M.

    2012-01-01

    Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasiv...

  13. Thrombopoietin expands hematopoietic stem cells after transplantation

    OpenAIRE

    Fox, Norma; Priestley, Greg; Papayannopoulou, Thalia; Kaushansky, Kenneth

    2002-01-01

    Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of...

  14. [Graves-Basedow disease after allogeneic bone marrow transplantation].

    Science.gov (United States)

    Jakubas, Beata; Kostecka-Matyja, Marta; Darczuk, Andrzej; Gil, Justyna

    2006-01-01

    One severe aplastic anaemia case who presented autoimmune thyroid disease after allogeneic bone marrow transplantation (alloBMT) is described. A 19 year old Polish girl developed Graves' hyperthyroidisms 19 months after allogeneic BMT for severe aplastic anaemia (SAA) donated from her brother. Her serum was positive for thyroid stimulating antibody (TSAb) and anti-thyroid peroxidase autoantibodies (aTPO) while her brother remained euthyroid, seronegative for TSAb, and showed no clinical signs of thyroid pathology. The genetic studies of lymphocytes FISH (fluorescence in situ hybridization) and analysis of STR (short tandem repeated) fragments suggested, that lymphocytes responsible for hyperthyroidisms were of donor origin. PMID:17133320

  15. Graves-Basedow disease after allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    One severe aplastic anaemia case who presented autoimmune thyroid disease after allogeneic bone marrow transplantation (alloBMT) is described. A 19 year old Polish girldeveloped Graves' hyperthyroidisms 19 months after allogeneic BMT for severe aplastic anaemia (SAA) donated from her brother. Her serum was positive for thyroid stimulating antibody (TSAb) and anti-thyroid peroxidase autoantibodies (aTPO) while her brother remained euthyroid, seronegative for TSAb, and showed no clinical signs of thyroid pathology. The genetic studies of lymphocytes FISH (fluorescence in situ hybridization) and analysis of STR (short tandem repeated) fragments suggested, that lymphocytes responsible for hyperthyroidisms were of donor origin. (author)

  16. SNP Array in Hematopoietic Neoplasms: A Review

    Science.gov (United States)

    Song, Jinming; Shao, Haipeng

    2015-01-01

    Cytogenetic analysis is essential for the diagnosis and prognosis of hematopoietic neoplasms in current clinical practice. Many hematopoietic malignancies are characterized by structural chromosomal abnormalities such as specific translocations, inversions, deletions and/or numerical abnormalities that can be identified by karyotype analysis or fluorescence in situ hybridization (FISH) studies. Single nucleotide polymorphism (SNP) arrays offer high-resolution identification of copy number variants (CNVs) and acquired copy-neutral loss of heterozygosity (LOH)/uniparental disomy (UPD) that are usually not identifiable by conventional cytogenetic analysis and FISH studies. As a result, SNP arrays have been increasingly applied to hematopoietic neoplasms to search for clinically-significant genetic abnormalities. A large numbers of CNVs and UPDs have been identified in a variety of hematopoietic neoplasms. CNVs detected by SNP array in some hematopoietic neoplasms are of prognostic significance. A few specific genes in the affected regions have been implicated in the pathogenesis and may be the targets for specific therapeutic agents in the future. In this review, we summarize the current findings of application of SNP arrays in a variety of hematopoietic malignancies with an emphasis on the clinically significant genetic variants.

  17. Fludarabine and melphalan conditioning with tacrolimus as GVHD prophylaxis for allogeneic stem cell transplant recipients is an effective reduced-intensity combination regimen compared to the conventional regimen

    International Nuclear Information System (INIS)

    As a reduced-intensity stem-cell transplantation (RIST) regimen, the combination of fludarabine and melphalan (FM) with an appropriate immunosuppressant reduces nonrelapse mortality (NRM). We retrospectively compared the efficacy of a RIST regimen with FM with that of a conventional stem cell transplantation (CST) regimen. Eighty-two consecutive hematological patients who underwent allogeneic stem-cell transplantation (SCT) at our hospital were enrolled. Preparation for RIST consisted of 25 mg/m2 fludarabine and melphalan 70 mg/m2. The conventional regimen employed high-dose cyclophosphamide and total-body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis for RIST consisted of tacrolimus alone or in conjunction with short-term methotrexate for unrelated donors. Of the 82 patients, 42 received the conventional CST regimen (median age, 35 years) and 40 received the RIST regimen (median age, 51 years). The probability of NRM was 17% (7/42) in the CST group and 8% (3/40) in the RIST group. Grade II to IV GVHD occurred in significantly more CST patients (38%) than RIST patients (28%). However, the overall survival was the same in the two groups (43%). The RIST regimen with FM incorporating tacrolimus and methotrexate demonstrated low treatment-related mortality (TRM) incidence and moderate control of GVHD and had efficacy comparable to that of the CST regimen, despite the advanced age of the RIST patient group. (author)

  18. Progress toward curing HIV infection with hematopoietic cell transplantation

    Directory of Open Access Journals (Sweden)

    Petz LD

    2015-07-01

    Full Text Available Lawrence D Petz,1 John C Burnett,2 Haitang Li,3 Shirley Li,3 Richard Tonai,1 Milena Bakalinskaya,4 Elizabeth J Shpall,5 Sue Armitage,6 Joanne Kurtzberg,7 Donna M Regan,8 Pamela Clark,9 Sergio Querol,10 Jonathan A Gutman,11 Stephen R Spellman,12 Loren Gragert,13 John J Rossi2 1StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 2Department of Molecular and Cellular Biology, Irell and Manella Graduate School of Biological Sciences, 3Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA; 4CCR5-Δ32/Δ32 Research Department, StemCyte International Cord Blood Center, Baldwin Park, CA, USA; 5Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6MD Anderson Cord Blood Bank, Department of Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Carolinas Cord Blood Bank, Duke University Medical Center, Durham, NC, USA; 8St Louis Cord Blood Bank, SSM Cardinal Glennon Children's Medical Center, St Louis, MO, USA; 9Enhance Quality Consulting Inc., Oviedo, FL, USA; 10Cell Therapy Service and Cord Blood Bank, Banc de Sang i Teixits, Barcelona, Spain; 11BMT/Hematologic Malignancies, University of Colorado, Aurora, CO, USA; 12Immunobiology and Observational Research, CIBMTR, Minneapolis, MN, USA; 13National Marrow Donor Program/Be The Match, Minneapolis, MN, USA Abstract: HIV-1 infection afflicts more than 35 million people worldwide, according to 2014 estimates from the World Health Organization. For those individuals who have access to antiretroviral therapy, these drugs can effectively suppress, but not cure, HIV-1 infection. Indeed, the only documented case for an HIV/AIDS cure was a patient with HIV-1 and acute myeloid leukemia who received allogeneic hematopoietic cell transplantation (HCT from a graft that carried the HIV-resistant CCR5-Δ32/Δ32 mutation. Other attempts to establish a cure for HIV

  19. Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Farnsworth Paul

    2012-09-01

    Full Text Available Abstract We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+ acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL effect.

  20. Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not contribute to significant islet cell regeneration once disease is established.

    Science.gov (United States)

    Kang, Elizabeth M; Zickler, Philipp P; Burns, Sean; Langemeijer, Saskia M; Brenner, Sebastian; Phang, Oswald A; Patterson, Noelle; Harlan, David; Tisdale, John F

    2005-06-01

    The treatment of type I diabetes by islet cell transplantation, while promising, remains restricted due to the incomplete efficacy and toxicity associated with current immunosuppression, and by limited organ availability. Given reports suggesting bone marrow derived stem cell plasticity, we sought to determine whether such cells could give rise to pancreatic islet cells in vivo. In the context of autoimmune diabetes, we transplanted unfractionated bone marrow from beta-gal trangenic donor mice into NOD mice prior to, at, and two weeks beyond the onset of disease. Successful bone marrow engraftment before diabetes onset prevented disease in all mice and for 1 year after transplant. However, despite obtaining full hematopoietic engraftment in over 50 transplanted mice, only one mouse became insulin independent, and no beta-Gal positive islets were detected in any of the mice. To test whether tolerance to islets was achieved, we injected islets obtained from the same allogeneic donor strain as the hematopoietic cells into 4 transplant recipients, and 2 had a reversion of their diabetes. Thus allogeneic bone marrow transplantation prevents autoimmune diabetes and tolerizes the recipient to donor islet grants, even in diabetic animals, yet the capacity of bone marrow derived cells to differentiate into functional islet cells, at least without additional manipulation, is limited in our model. PMID:15911094

  1. Flow cytometry data analysis of CD34+/CD133+ stem cells in bone marrow and peripheral blood and T, B, and NK cells after hematopoietic grafting.

    Science.gov (United States)

    Jaime-Pérez, José C; Villarreal-Villarreal, César D; Vázquez-Garza, Eduardo; Méndez-Ramírez, Nereida; Salazar-Riojas, Rosario; Gómez-Almaguer, David

    2016-06-01

    This article provides flow cytometry information regarding levels of expression for hematopoietic stem cell markers CD34 and CD133 obtained simultaneously of the bone marrow and peripheral blood from recipients of allogeneic and autologous transplants of PB hematoprogenitors for treating hematological malignancies and who were clinically healthy after ≥100 days following the procedure. CD34 and CD133 expression is compared regarding type of transplant (autologous vs. allogeneic) and sample cell source (bone marrow vs. peripheral blood). Patients were conditioned with a reduced-intensity conditioning regimen. Also shown is the flow cytometry analysis of mononuclear cell and lymphocyte populations in the peripheral blood of both types of recipients, as well as the characterization of immune cells, including T lymphocyte antigenic make up markers CD3, CD4 and CD8, B lymphocytes and NK cells, including total NK, bright and dim subtypes in the peripheral blood of both types of recipients. For further information and discussion regarding interpretation and meaning of post-transplant flow cytometry analysis, please refer to the article "Assessment of immune reconstitution status in recipients of a successful hematopoietic stem cell transplant from peripheral blood after reduced intensity conditioning" [1]. PMID:27115030

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

    International Nuclear Information System (INIS)

    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

  3. Combination antifungal therapy and surgery for the treatment of invasive pulmonary aspergillosis after hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Tiziana Toffolutti

    2011-06-01

    Full Text Available An 8-year old boy, affected by severe aplastic anemia, developed a probable pulmonary invasive aspergillosis (IA early after a second unrelated allogeneic hematopoietic stem cell transplant (HSCT. He was treated promptly with the combination of liposomal amphotericin B and caspofungin. Despite the initial stabilization, the patient deteriorated and the antifungal therapy was switched to voriconazole and caspofungin. The patient gradually improved and was discharged home on day +29 post-HSCT on oral voriconazole. On day +119, a sudden episode of hemoptysis occurred and a right superior lobectomy was decided to remove the residual aspergilloma. The patient is now alive and well more than 24 months from HSCT. This case demonstrated that antifungal combination therapy and surgery are valid options to cure pulmonary IA even in patients at high-risk and severely immunosuppressed.

  4. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete;

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... risk of skin cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and...... highest for RTRs. Autologous HSCT recipients had no increased risk of skin cancer. CONCLUSIONS AND RELEVANCE: Allogeneic HSCT recipients have an increased risk of BCC, SCC, and MM. Total-body irradiation was a major determinant for BCC. Our findings indicate the relevance of dermatologic follow-up in HSCT...

  5. Hodgkin's disease as unusual presentation of post-transplant lymphoproliferative disorder after autologous hematopoietic cell transplantation for malignant glioma

    Directory of Open Access Journals (Sweden)

    Scelsi Mario

    2005-08-01

    Full Text Available Abstract Background Post-transplant lymphoproliferative disorder (PTLD is a complication of solid organ and allogeneic hematopoietic stem cell transplantation (HSCT; following autologous HSCT only rare cases of PTLD have been reported. Here, a case of Hodgkin's disease (HD, as unusual presentation of PTLD after autologous HSCT for malignant glioma is described. Case presentation 60-years old man affected by cerebral anaplastic astrocytoma underwent subtotal neurosurgical excision and subsequent high-dose chemotherapy followed by autologous HSCT. During the post HSCT course, cranial irradiation and corticosteroids were administered as completion of therapeutic program. At day +105 after HSCT, the patient developed HD, nodular sclerosis type, with polymorphic HD-like skin infiltration. Conclusion The clinical and pathological findings were consistent with the diagnosis of PTLD.

  6. Advance in hematopoietic stem cells transplantation for leukemia

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiao-jun

    2008-01-01

    @@ During the past 50 years, intensive studies into the characteristics of hematopoietic stem cell transplantation immunology and the emergence of new immunosuppressant and anti-infective drugs have significantly improved the clinical result of hematopoietic stem cell transplantation (HSCT).

  7. Moving Beyond Autologous Transplantation in Multiple Myeloma: Consolidation, Maintenance, Allogeneic Transplant, and Immune Therapy.

    Science.gov (United States)

    Krishnan, Amrita; Vij, Ravi; Keller, Jesse; Dhakal, Binod; Hari, Parameswaran

    2016-01-01

    For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses. Though the consolidation strategy remains largely confined to clinical trials, significant data support the efficacy of consolidation in improving the depth of response and outcomes. There are also increasing rates of minimal residual disease-negativity with additional consolidation therapy. On the other hand, maintenance with novel agents post-transplant is well established and has been shown to improve both progression-free and overall survival. Evolving paradigms in maintenance include the use of newer proteasome inhibitors, immunotherapy maintenance, and patient-specific maintenance-a concept that utilizes minimal residual disease as the primary driver of decisions regarding starting or continuing maintenance therapy. The other approach to overcome residual disease is immune therapeutic strategies. The demonstration of myeloma-specific alloimmunity from allogeneic transplantation is well established. More sophisticated and promising immune approaches include adoptive cellular therapies, tumor vaccines, and immune checkpoint manipulations. In the future, personalized minimal residual disease-driven treatment strategies following ASCT will help overcome the residual disease, restore multiple myeloma-specific immunity, and achieve sustained disease control while minimizing the risk of overtreatment. PMID:27249701

  8. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation.

    Science.gov (United States)

    Schmid, Christoph; Labopin, Myriam; Socié, Gerard; Daguindau, Etienne; Volin, Liisa; Huynh, Anne; Bourhis, Jean Henri; Milpied, Noel; Cornelissen, Jan; Chevallier, Patrice; Maertens, Johan; Jindra, Pavel; Blaise, Didier; Lenhoff, Stig; Ifrah, Norbert; Baron, Frédéric; Ciceri, Fabio; Gorin, Claude; Savani, Bipin; Giebel, Sebastian; Polge, Emmanuelle; Esteve, Jordi; Nagler, Arnon; Mohty, Mohamad

    2015-10-22

    To analyze the influence of distinct combinations of molecular aberrations on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for cytogenetically normal acute myeloid leukemia (CN-AML), a retrospective registry analysis was performed on 702 adults undergoing HSCT in first complete remission (CR). Patients were grouped according to presence or absence of NPM1 mutations (NPM1(mut)) and FLT3 internal tandem duplications (FLT3-ITD). Double-negative patients were evaluated for mutations of the CCAAT/enhancer binding protein α gene (CEBPα). The influence of genotypes on relapse, non-relapse mortality, leukemia-free survival (LFS) and overall survival (OS), and a prognostic classification combining NPM1/FLT3-ITD profile and classical risk factors were calculated. Two-year OS from HSCT was 81 ± 5% in NPM1(mut)/FLT3(wt), 75 ± 3% in NPM1(wt)/FLT3(wt), 66 ± 3% in NPM1(mut)/FLT3-ITD, and 54 ± 7% in NPM1(wt)/FLT3-ITD (P = .003). Analysis of CEBPα among patients with NPM1(wt)/FLT3(wt) revealed excellent results both in patients with CEBPα(mut) and with a triple negative genotype (2-year OS: 100%/77 ± 3%). In a Cox-model of predefined variables, age, FLT3-ITD and >1 course of chemotherapy to reach CR were risk factors associated with inferior outcome, regardless of NPM1 mutational status, variations of transplant protocols, or development of graft-versus-host disease. In a prognostic risk classification, 2-year OS/LFS rates were 88 ± 3%/79 ± 4% without any, 77 ± 2%/73 ± 3% with one, and 53 ± 4%/50 ± 4 with ≥2 risk factors (P = .003/.002). PMID:26351297

  9. Conditioning with rabbit versus horse ATG dramatically alters clinical outcomes in identical twins with severe aplastic anemia transplanted with the same allogeneic donor.

    Science.gov (United States)

    Vo, P T; Pantin, J; Ramos, C; Cook, L; Cho, E; Kurlander, R; Khuu, H; Barrett, J; Leitman, S; Childs, R W

    2015-01-01

    Severe aplastic anemia (SAA) is a rare disorder leading to bone marrow failure, which if left untreated, is invariably fatal. Conventional therapies with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (HSCT) are highly effective. HSCT can offer a greater outcome in younger patients who have an available HLA match-related donor. Recent studies showing the addition of antithymocyte globulin (ATG) to the conditioning regimen improves engraftment and reduces the risk of graft-versus-host disease (GVHD).There are currently two ATG preparations in the USA, equine (or horse) and rabbit ATG. These agents are pharmacologically distinct, having significant differences in their pharmacokinetics and in vivo immunosuppressive effects [N Engl J Med 365(5):430-438, 2011]. Here, we report a case of two monozygotic twins with constitutional SAA that evolved to myelodysplastic syndrome (MDS) who both underwent allogeneic peripheral blood stem cell transplantation (PBSC) from the same single HLA antigen mismatched sibling donor with the only difference in the transplant regimen being the type of ATG used in the preparative regimen; one twin received horse ATG and the other received rabbit ATG during conditioning. This report emphasizes that dramatic differences in donor T cell chimerism and clinical outcomes including GVHD can occur as a consequence of the type of ATG that is utilized in the transplant conditioning regimen. These differences highlight that these agents should not be considered interchangeable drugs when used in this setting. PMID:26113077

  10. Effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on hemopoiesis and survival rate following allogeneic bone marrow transplantation in mice

    International Nuclear Information System (INIS)

    The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) were examined. Specific pathogen-free (SPF) C3H mice and germ-free C3H mice, kept in an isolator for germ-free animals, received 10 Gy of total body irradiation (TBI) and all the mice died by day 9 after TBI. These survival rates were improved by BMT. In the case of SPF mice, survival rates at 14 and 100 days were 33% (12/36), 17% (6/36) and in the case of germ-free mice they were 79% (15/19), 74% (14/19) respectively. When SPF mice received rhG-CSF (30 μg/kg/day) subcutaneously for 14 consecutive days following BMT, their survival rates were improved to 79% (30/38), 79% (30/38) respectively. The survival rate of rhG-CSF treated SPF mice were equal to that of germ-free mice. When the effect of rhG-CSF treatment on hemopoiesis of SPF mice after allogeneic BMT was examined varous hematopoietic progenitor cells in the bone marrow and spleen increased until day 10 after, BMT, while only neutrophils increased in the peripheral blood during the period. No adverse effects of rhG-CSF after BMT, the neutrophil recovered in counts quickly and increased neutrophil prevented endogenous infections and improved the survival rate without apparent complications. (author)

  11. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

    Science.gov (United States)

    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID:26687013

  12. Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

    Science.gov (United States)

    Gori, E; Arpinati, M; Bonifazi, F; Errico, A; Mega, A; Alberani, F; Sabbi, V; Costazza, G; Leanza, S; Borrelli, C; Berni, M; Feraut, C; Polato, E; Altieri, M C; Pirola, E; Loddo, M C; Banfi, M; Barzetti, L; Calza, S; Brignoli, C; Bandini, G; De Vivo, A; Bosi, A; Baccarani, M

    2007-03-01

    Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT. PMID:17277790

  13. Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Elfenbein, G.J.; Brogaonkar, D.S.; Bias, W.B.

    1978-09-01

    A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality (45, X, -X, t(8;21) (q22; q22)) was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.

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

    DEFF Research Database (Denmark)

    Shamim, Z; Spellman, S; Haagenson, M;

    2013-01-01

    significance of IL-7Rα SNP genotypes in 590-recipient/donor pairs that received HLA-matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis....... The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL-7 pathway and IL-7Rα SNPs in HCT....

  15. Extracorporeal Photopheresis for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation

    OpenAIRE

    Shaughnessy, Paul J; Bolwell, Brian J.; van Besien, Koen; Mistrik, Martin; Grigg, Andrew; Dodds, Anthony; Prince, H. Miles; Durrant, Simon; Ilhan, Osman; Parenti, Dennis; Rogers, Jon; Gallo, Jose; Foss, Francine; Apperley, Jane; Zhang, Mei-Jie

    2009-01-01

    Graft-versus-host disease (GVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photopheresis (ECP) can modulate APC function and benefit some patients with GVHD. We report the results of a study using ECP administered prior to a standard myeloablative preparative regimen intended to prevent GVHD. Grade II-IV aGVHD developed in 9 (30%) of 30 recipients of HLA-matched related transplants and 13 (42%) of 31 recipients of HLA-matched unrela...

  16. Human herpesvirus-6 viremia is not associated with poor clinical outcomes in children following allogeneic hematopoietic cell transplantation.

    Science.gov (United States)

    Violago, Leah; Jin, Zhezhen; Bhatia, Monica; Rustia, Evelyn; Kung, Andrew L; Foca, Marc D; George, Diane; Garvin, James H; Sosna, Jean; Robinson, Chalitha; Karamehmet, Esra; Satwani, Prakash

    2015-11-01

    HHV-6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV-6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV-6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV-6, CMV, EBV, and ADV. HHV-6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3-26.7%) of patients had HHV-6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15-day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV-6 viremia (58%) than in those without HHV-6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV-6 viremia in multivariate analysis. Similarly, HHV-6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV-6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV-6 PCR should only be performed on clinical suspicion. PMID:26329541

  17. The influence of interleukin-7 receptor α-chain haplotypes on outcome after allogeneic hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Broux, B; Shamim, Z; Wang, T; Spellman, S; Haagenson, M; Stinissen, P; Ryder, L P; Müller, K; Hellings, N

    2014-01-01

    We investigated the influence of IL-7 receptor α-chain (IL-7Rα) gene haplotypes in donors on the outcome of haematopoietic cell transplantation (HCT). Unlike the association between single donor SNPs and HCT outcome found previously, only trends towards association were found here, due to 'dilution...

  18. Human hematopoietic cell culture, transduction, and analyses

    DEFF Research Database (Denmark)

    Bonde, Jesper; Wirthlin, Louisa; Kohn, Donald B;

    2008-01-01

    This unit provides methods for introducing genes into human hematopoietic progenitor cells. The Basic Protocol describes isolation of CD34(+) cells, transduction of these cells with a retroviral vector on fibronectin-coated plates, assaying the efficiency of transduction, and establishing long......-term cultures. Support protocols describe methods for maintenance of vector-producing fibroblasts (VPF) and supernatant collection from these cells, screening medium components for the ability to support hematopoietic cell growth, and establishing colonies from long-term cultures. Other protocols provide PCR...

  19. Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

    International Nuclear Information System (INIS)

    To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

  20. Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yun Hee; Kim, Ji Yoon; Choi, Byung Ock; Ryu, Mi Ryeong; Chung, Su Mi [Dept. of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2012-12-15

    To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.