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Successful mismatched hematopoietic stem cell transplantation for pediatric hemoglobinopathy by using ATG and post-transplant cyclophosphamide.

Bone Marrow Transplant 2021 May 3. Epub 2021 May 3.

Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.

The use of HLA-mismatched (un)related donors is historically associated with a higher incidence of transplant-related complications and mortality. However, the use of such donors may overcome the limited availability of HLA-matched donors for patients with β-thalassemia major (TM) and sickle cell disease (SCD). We investigated hematopoietic stem cell transplantation (HSCT) outcomes of pediatric TM and SCD patients treated with a mismatched donor using a treosulfan-based conditioning in combination with ATG and post-transplant cyclophosphamide (PT-CY) and compared these results to the clinical outcome of patients treated by matched donor HSCT without PT-CY. Read More

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Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India.

Front Immunol 2021 16;12:627651. Epub 2021 Apr 16.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Wiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India. Read More

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Comparison of mitoxantrone-melphalan and BEAM conditioning regimens in patients with lymphoma.

Hematol Oncol Stem Cell Ther 2021 Apr 17. Epub 2021 Apr 17.

Gaziantep University, Faculty of Medicine, Department of Hematology, Gaziantep, Turkey.

Objective/background: Lymphoma is seen as a highly treatable and curable malignancy with aggressive treatment methods. Efficacy is often limited by toxicity and many patients need alternative treatment strategies as they cannot tolerate existing high cytotoxic approaches. Our aim is to compare BEAM [carmustine (BCNU), etoposide, cytarabine (ARA-C, cytosine arabinoside), and melphalan] and mitoxantrone-melphalan (Mx-Mel) regimens utilized in our patients with a diagnosis of lymphoma who underwent autologous stem cell transplantation (ASCT), and to demonstrate that the Mx-Mel regimen has similar but less toxic results than the BEAM regimen we have been using frequently as standard conditioning regimen. Read More

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Sarcopenia Screening Allows Identifying High-Risk Patients for Allogenic Stem Cell Transplantation.

Cancers (Basel) 2021 Apr 8;13(8). Epub 2021 Apr 8.

Center for Internal Medicine, Division of Sports and Rehabilitation Medicine, Ulm University Medical Center, 89073 Ulm, Germany.

Allogenic stem cell transplantation (aSCT) is the only potentially curative treatment for high-risk hematological diseases. Despite advancements in supportive measures, aSCT outcome is still affected by considerable transplant-related mortality. We implemented a new sarcopenia assessment prior to aSCT to evaluate its predictive capability for all-cause and non-relapse mortality. Read More

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Upfront transplantation may have better outcomes than pre-transplant cytoreductive therapy for treating patients with MDS-EB-1 or MDS-EB-2.

Int J Cancer 2021 Apr 25. Epub 2021 Apr 25.

Department of Hematology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Blvd North, Guangzhou, China.

Whether patients with myelodysplastic syndrome undergoing allo-HSCT benefit from pre-transplant cytoreductive therapy remains controversial. This study compared the outcomes of upfront transplantation with those of pre-transplant cytoreductive therapy in the patients who received transplantation and those who dropped out due to cytoreductive therapy-related adverse effects. Patients with MDS-EB-1 or MDS-EB-2 were enrolled and divided into 3 groups based on therapy pre-transplantation: upfront transplantation (upfront, n=54); induction chemotherapy (CT, n=66); hypomethylating agents alone (HMA, n=37). Read More

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Low levels of plasmacytoid dendritic cells at engraftment are a valuable prognostic indicator in children receiving allogeneic hematopoietic stem cell transplantation.

Transplant Cell Ther 2021 Apr 22. Epub 2021 Apr 22.

Department of Hematology, Children Hospital, Soochow University, Suzhou, China. Electronic address:

Background: Early prediction and intervention are known to be critical for acute graft-versus-host disease (aGvHD) prevention and treatment. Significant progress has been made in the development of human plasma biomarkers for the risk stratification of aGvHD severity. Whether donor-derived immune cells may predict the occurrence of severe aGvHD early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains poorly understood. Read More

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The time-dependent effects of early-onset Epstein-Barr viremia on adult acute leukemia patients following allo-HSCT with ATG-containing MAC regimen.

Ann Hematol 2021 Apr 22. Epub 2021 Apr 22.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China.

Epstein-Barr virus (EBV) viremia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the impacts of early-onset EBV viremia in acute leukemia (AL) patients who underwent allo-HSCT with anti-thymocyte globulin (ATG)-containing myeloablative conditioning (MAC) regimen. Two hundred and ninety-six patients were included between January 2013 and December 2015. Read More

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The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets.

Haematologica 2021 Apr 22. Epub 2021 Apr 22.

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY.

Microbiota injury occurs in many patients undergoing allogeneic hematopoietic cell transplantation, likely as a consequence of conditioning regimens involving chemo- and radiotherapy, the widespread use of both prophylactic and therapeutic antibiotics, and profound dietary changes during the peri-transplant period. Peri-transplant dysbiosis is characterized by a decrease in bacterial diversity, loss of commensal bacteria and single-taxon domination (e.g. Read More

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Safety of surgical fertility preservation procedures in children prior to Hematopoietic Stem Cell Transplant.

Transplant Cell Ther 2021 Apr 14. Epub 2021 Apr 14.

Division of Pediatric Oncology, Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA; Department of Pediatrics, Harvard University Medical School, Boston, MA.

Background: Long-term survival following hematopoietic stem cell transplant (HSCT) in childhood continues to improve and patients are thus increasingly faced with the late effects of treatment. Infertility is very common for both males and females following HSCT and is one of the most distressing sequelae. Adoption and surrogate egg or sperm donation are possibilities for some patients but post-HSCT reversal of gonadal failure is not possible. Read More

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Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation.

Bone Marrow Transplant 2021 Apr 16. Epub 2021 Apr 16.

Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK.

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. Read More

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Hematopoietic Stem Cell Transplantation in T-cell and NK-cell lymphomas-Update on Recent Advances.

Transplant Cell Ther 2021 Apr 12. Epub 2021 Apr 12.

Department of Hematology-Oncology, National University Cancer Institute, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Mature T- and natural killer (NK)-cell non-Hodgkin lymphoma (T-cell NHL) have a poor prognosis. Data from existing retrospective and prospective studies has suggested that high-dose chemotherapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) may improve the survival in patients with chemosensitive disease, either in the upfront or salvage setting. Auto-HCT is currently recommended to be used as frontline consolidation in peripheral T-cell lymphoma not otherwise specified (PTCL-nos), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma-anaplastic lymphoma kinase (ALCL-ALK) negative, NK/T-cell (disseminated), and enteropathy-associated T-cell lymphoma (EATL). Read More

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Improved transplant outcomes with myeloablative conditioning for hemophagocytic lymphohistiocytosis in HLA-matched and mismatched donors: a national multicenter retrospective study.

Bone Marrow Transplant 2021 Apr 12. Epub 2021 Apr 12.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

We report the results of national retrospective study of 45 children with hemophagocytic lymphohistiocytosis (HLH) who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) in Israel between the years 2000-2018. Donors were either HLA-matched (n = 26), partially mismatched (n = 7), haploidentical (n = 8), or cord-blood (n = 4). Myeloablative conditioning (MAC) was used in 20 procedures, and reduced-intensity conditioning (RIC) in 25. Read More

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Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation.

J Clin Oncol 2021 Apr 9:JCO2003643. Epub 2021 Apr 9.

Anthony Nolan Research Institute, Royal Free Hospital, London, UK.

Purpose: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study. Read More

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Allogeneic stem cell transplantation for mantle cell lymphoma-update of the prospective trials of the East German Study Group Hematology/Oncology (OSHO#60 and #74).

Ann Hematol 2021 Apr 8. Epub 2021 Apr 8.

Department of Internal Medicine C - Haematology and Oncology, Stem Cell Transplantation, Palliative Care - University of Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.

Mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma with an often aggressive course, incurable by chemotherapy. Consolidation with high-dose therapy and autologous stem cell transplantation (autoSCT) has a low transplant-related mortality but does not lead to a survival plateau. Allogeneic stem cell transplantation (alloSCT) is associated with a higher early mortality, but can cure MCL. Read More

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LMP7 polymorphism may modify the presentation and clinical impact of minor histocompatibility antigens in matched related hematopoietic stem cell transplantation.

Cell Immunol 2021 Jun 9;364:104329. Epub 2021 Mar 9.

Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt; Bone Marrow Transplantation Unit, Nasser Institute Hospital for Research and Treatment, Cairo, Egypt.

Differential expression of minor histocompatibility antigens between the recipient and donor determines their disparity and can be modified by immunoproteasomes that regulate their processing and presentation. We examined the impact of HA-1 and HA-8 disparity, and immunoproteasome LMP7 polymorphism in 130 pairs. In multivariate analysis, HA-1 disparity showed a statistically significant association with an increased incidence of acute graft-versus-host disease (aGVHD) II-IV (p = 0. Read More

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[Experience of the Spanish Group for Hematopoietic Transplantation (GETMON-GETH) in allogenic hematopoietic stem cell transplantation in Philadelphia acute lymphoblastic leukemia].

An Pediatr (Barc) 2021 Mar 26. Epub 2021 Mar 26.

Hemato-Oncología Pediátrica, Hospital Universitario La Paz, Madrid, España. Electronic address:

Introduction: Outcomes in patients diagnosed of acute lymphoblastic leukemia with Philadelphia chromosome (Ph-ALL) remains unfavourable compared to other subtypes of acute lymphoblastic leukemia despite improvements in drug treatments as well as advances in hematopoietic stem cell transplantation (HSCT).

Patients And Methods: The role of allogeneic HSCT in Ph-ALL patients has been analysed through a multicentric study where data belonging to 70 patients diagnosed of this entity in different center that received HSCT between years 1998 and 2014, were reported by the Grupo Español de Trasplante Hematopoyético (GETH).

Results: The performance of HSCT from year 2004, in first complete remission (CR) status with thymoglobulin (ATG) based conditioning had a favorable impact on overall survival (OS). Read More

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Large Granular Lymphocytosis With Cytopenias After Allogeneic Blood or Marrow Transplantation: Clinical Characteristics and Response to Immunosuppressive Therapy.

Transplant Cell Ther 2021 Mar 16;27(3):260.e1-260.e6. Epub 2020 Dec 16.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address:

Large granular lymphocytosis (LGL)-or LGL leukemia-is a T- or NK-cell lymphoproliferative disorder that often results in cytopenias and autoimmune phenomena. Several studies have described LGL in a subset of patients after allogeneic blood or marrow transplantation (alloBMT), almost exclusively in the setting of asymptomatic lymphocytosis. Some have suggested an association with improved transplant-related outcomes. Read More

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Successful management of T-cell mediated rejection in a recent kidney transplant recipient with COVID-19 associated severe acute respiratory syndrome.

Transpl Infect Dis 2021 Mar 29:e13598. Epub 2021 Mar 29.

Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine, Madison, WI, USA.

COVID-19-associated vasculitis has been reported as a defining feature of systemic disease including acute kidney injury. However, the understanding of COVID-19 kidney transplant-related injuries is still evolving. We report a case of AKI with isolated vasculitis (v2 lesion) in a new kidney transplant recipient with COVID-19 pneumonia. Read More

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Outcomes of adult T-Cell leukemia/lymphoma with allogeneic stem cell transplantation: single-institution experience.

Leuk Lymphoma 2021 Mar 29:1-7. Epub 2021 Mar 29.

Adult BMT Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Few publications exist concerning allogeneic hematopoietic cell transplant (alloHCT) outcomes in non-Japanese patients with HTLV-1-associated ATLL. We detail the patient and disease characteristics, transplant approach, and clinical outcomes in 17 patients with ATLL at our institution who underwent alloHCT. We report favorable outcomes, with 8/17 in ongoing remission, 2/17 with prolonged (>6 years) disease-free survival, and a low incidence of transplant-related mortality (2/17). Read More

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Myeloablative versus Reduced-Intensity Conditioning for Hematopoietic Cell Transplantation in Acute Myelogenous Leukemia and Myelodysplastic Syndromes-Long-Term Follow-Up of the BMT CTN 0901 Clinical Trial.

Transplant Cell Ther 2021 Feb 26. Epub 2021 Feb 26.

Duke University, Durham, North Carolina.

Several prospective randomized trials comparing conditioning intensity before allogeneic hematopoietic cell transplantation (HCT) have been performed, with conflicting results. Although reduced-intensity conditioning (RIC) leads to lower treatment-related mortality (TRM), this is offset by higher rates of relapse. Long-term follow-up of randomized comparative trials are limited. Read More

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February 2021

A prognostic score including mutation profile and clinical features for patients with CMML undergoing stem cell transplantation.

Blood Adv 2021 Mar;5(6):1760-1769

Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The inclusion of mutation status improved risk stratification for newly diagnosed patients with chronic myelomonocytic leukemia (CMML). Stem cell transplantation is a potentially curative treatment option, and patient selection is critical because of relevant transplant-related morbidity and mortality. We aimed to evaluate the impact of mutation status together with clinical presentations on posttransplant outcome. Read More

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Effectiveness of hyperbaric oxygen therapy for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

Int J Hematol 2021 Mar 16. Epub 2021 Mar 16.

Department of Hematology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8640, Japan.

Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2. Read More

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Immunomodulating functions of human leukocyte antigen-G and its role in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Ann Hematol 2021 Mar 11. Epub 2021 Mar 11.

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy to treat several hematological malignancies and non-hematological malignancies. However, graft-versus-host disease (GVHD) is a frequent and serious transplant-related complication which dramatically restrains the curative effect of allo-HSCT and a significant cause of morbidity and mortality in allogeneic HCT recipients. Effective prevention of GVHD mainly depends on the induction of peripheral immune tolerance. Read More

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Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.

Front Immunol 2021 23;12:611910. Epub 2021 Feb 23.

Departments of Surgery and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Detrimental inflammatory responses after solid organ transplantation are initiated when immune cells sense pathogen-associated molecular patterns (PAMPs) and certain damage-associated molecular patterns (DAMPs) released or exposed during transplant-associated processes, such as ischemia/reperfusion injury (IRI), surgical trauma, and recipient conditioning. These inflammatory responses initiate and propagate anti-alloantigen (AlloAg) responses and targeting DAMPs and PAMPs, or the signaling cascades they activate, reduce alloimmunity, and contribute to improved outcomes after allogeneic solid organ transplantation in experimental studies. However, DAMPs have also been implicated in initiating essential anti-inflammatory and reparative functions of specific immune cells, particularly Treg and macrophages. Read More

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February 2021

Contemporary haploidentical stem cell transplant strategies in children with hematological malignancies.

Authors:
Ravi M Shah

Bone Marrow Transplant 2021 Mar 5. Epub 2021 Mar 5.

Section of Oncology and BMT, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.

The barriers to HLA-mismatched or haploidentical hematopoietic stem cell transplantation (HSCT), namely GvHD and graft failure, have been overcome with novel transplant platforms. Post-transplant Cyclophosphamide (PTCy) is widely available, feasible and easy to implement. TCRαβ T and B cell depletion comes with consistent GvHD preventive benefits irrespective of age and indication. Read More

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Role of Stem Cell Transplantation in Multiple Myeloma.

Cancers (Basel) 2021 Feb 18;13(4). Epub 2021 Feb 18.

Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center Columbus, Columbus, OH 43210, USA.

Autologous stem cell transplantation (auto-SCT) has been the standard of care in eligible newly diagnosed multiple myeloma (MM) patients. Outcomes of patients with MM have improved significantly due to the advent of several novel drugs. Upfront use of these drugs in induction therapy has significantly increased the rate and depth of responses that have translated into longer remission and survival. Read More

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February 2021

HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia.

Blood Adv 2021 Mar;5(5):1333-1339

Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Scientific Institute for Research and Healthcare (IRCCS) Bambino Gesù Children's Hospital, Rome, Italy.

We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Read More

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[Potential of ultrasound in allogeneic stem cell transplantation and transplant-related complications].

Z Gastroenterol 2021 Apr 25;59(4):336-344. Epub 2021 Feb 25.

Interdisziplinäres Ultraschallzentrum, UKGM Marburg.

Allogeneic hematopoietic stem cell transplantation (HCT) is a complex therapeutic procedure causing significant morbidity and mortality, including the gastrointestinal tract. Early diagnosis and treatment of HCT-associated complications are, therefore, of utmost importance to improve overall HCT outcome. Sonography can be a powerful diagnostic tool and is easily accessible at the bedside of HCT patients. Read More

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Analysis of HLA haplotype and clinical factors during hematopoietic stem cell transplantation.

Transpl Immunol 2021 Feb 19;66:101376. Epub 2021 Feb 19.

First Department of Internal Medicine, Kansai Medical University, Japan. Electronic address:

Background: The human leukocyte antigen (HLA) haplotype of the recipient in hematopoietic stem cell transplantation (HSCT) is a key factor in its success or failure. We analyzed the relationship between HLA haplotype frequency and associated clinical factors in HSCT patients.

Methods: Patients who underwent allogeneic HSCT between 2000 and 2019 at our institution were enrolled in this study. Read More

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February 2021

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome after hematopoietic stem cell transplantation for thalassemia major: incidence, management, and outcome.

Bone Marrow Transplant 2021 Feb 19. Epub 2021 Feb 19.

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Hepatic veno-occlusive disease or sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present prospective study, we aimed to investigate the incidence, management, and outcome of VOD/SOS in patients with thalassemia major (TM) who received allo-HSCT. VOD/SOS was diagnosed and classified based on the modified Seattle criteria. Read More

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February 2021