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Therapeutic strategies, including allogeneic stem cell transplantation, to overcome relapsed/refractory adult T-cell acute lymphoblastic leukemia.

Expert Rev Hematol 2021 Jul 27. Epub 2021 Jul 27.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.

Introduction: The long-term survival of relapsed/refractory (R/R) adult T-cell acute lymphoblastic leukemia (T-ALL) is quite poor, and early T-cell precursor (ETP) ALL has recently been described as a high-risk T-ALL subgroup. However, the optimal therapeutic approach to R/R adult T-ALL remains poorly established.

Areas Covered: At present, cytoreductive therapy followed by allogeneic stem cell transplantation (allo-SCT) is considered to be the most clinically relevant and curative modality for R/R T-ALL. Read More

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BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study.

Lancet Neurol 2021 Aug;20(8):639-652

Hematology Branch, Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.

Background: Progressive multifocal leukoencephalopathy, a rare disease of the CNS caused by JC virus and occurring in immunosuppressed people, is typically fatal unless adaptive immunity is restored. JC virus is a member of the human polyomavirus family and is closely related to the BK virus. We hypothesised that use of partly HLA-matched donor-derived BK virus-specific T cells for immunotherapy in progressive multifocal leukoencephalopathy would be feasible and safe. Read More

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Hematopoietic Stem Cell Transplantation For Patients With Autosomal Recessive Complete Interferon Gamma Receptor 2 Deficiency: Experience In Oman.

Transplant Cell Ther 2021 Jul 19. Epub 2021 Jul 19.

Department of, Hematology, Sultan Qaboos University Hospital, Muscat, Oman; Apollo Hospital, Muscat, Oman. Electronic address:

Autosomal recessive complete interferon- gamma receptor-2 (IFN-γR2) deficiency is a rare potentially fatal primary immune deficiency that predisposes to disseminated mycobacterial disease.Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment. Few patients had been reported so far. Read More

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Rituximab Desensitization in Liver Transplant Recipients With Preformed Donor-specific HLA Antibodies: A Japanese Nationwide Survey.

Transplant Direct 2021 Aug 16;7(8):e729. Epub 2021 Jul 16.

Department of Gastroenterological Surgery, Institute of Gastroenterology, Tokyo Women's Medical University of Medicine, Tokyo, Japan.

Background: The significance of preformed donor-specific anti-HLA antibodies (DSAs) in liver transplant recipients is controversial. Moreover, there has been no established desensitization protocol for DSA-positive recipients.

Methods: A Japanese nationwide survey was performed to investigate the clinical practice among preformed DSA-positive patients with special reference to rituximab desensitization. Read More

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Preemptive donor-derived anti-CD19 CAR T-cell infusion showed a promising anti-leukemia effect against relapse in MRD-positive B-ALL after allogeneic hematopoietic stem cell transplantation.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

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Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Cancer Immunol Immunother 2021 Jul 19. Epub 2021 Jul 19.

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Read More

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Second unmanipulated allogeneic transplantation could be used as a salvage option for patients with relapsed acute leukemia post-chemotherapy plus modified donor lymphocyte infusion.

Front Med 2021 Jul 19. Epub 2021 Jul 19.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, 100044, China.

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Read More

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Case Report: Effects of Anti-SARS-CoV-2 Convalescent Antibodies Obtained With Double Filtration Plasmapheresis.

Front Immunol 2021 30;12:711915. Epub 2021 Jun 30.

Departments of Renal Medicine, Rare Diseases and Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. Read More

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Unmanipulated Stem Cell Boost for Mixed Chimerism in Transfusion Dependent Thalassemia.

Indian J Hematol Blood Transfus 2021 Jul 3;37(3):458-462. Epub 2020 Sep 3.

Department of Medical Oncology, Gujarat Cancer and Research Institute, Ahmedabad, Gujarat 380016 India.

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. Read More

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Dendritic Cell-Mediated Regulation of Liver Ischemia-Reperfusion Injury and Liver Transplant Rejection.

Front Immunol 2021 28;12:705465. Epub 2021 Jun 28.

Department of Surgery, Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Liver allograft recipients are more likely to develop transplantation tolerance than those that receive other types of organ graft. Experimental studies suggest that immune cells and other non-parenchymal cells in the unique liver microenvironment play critical roles in promoting liver tolerogenicity. Of these, liver interstitial dendritic cells (DCs) are heterogeneous, innate immune cells that appear to play pivotal roles in the instigation, integration and regulation of inflammatory responses after liver transplantation. Read More

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Mixed T cell lineage chimerism in acute leukemia/MDS using pre-emptive donor lymphocyte infusion strategy-Is it prognostic?-a single-center retrospective study.

Blood Cancer J 2021 Jul 12;11(7):128. Epub 2021 Jul 12.

Department of Haematological malignancies and stem cell transplant, Kings College hospital NHS trust, London, UK.

Pre-emptive DLI (pDLI) is an effective strategy in lowering the risk of relapse without significantly increasing the risk of graft-versus-host disease (GVHD) in the case of T cell lineage mixed chimerism (MC) post allogeneic transplant in hematological malignancies. Many patients, however, fail to receive timely pDLI and have dismal outcomes, which are not taken into consideration. We compared long-term outcomes of 106 patients having T cell MC after day 60 and undergoing allogeneic stem cell allograft for acute leukemia from an unrelated donor (UD), with 111 patients having complete chimerism (CC). Read More

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Improved hematopoietic stem cell transplantation upon inhibition of natural killer cell-derived interferon-gamma.

Stem Cell Reports 2021 Jun 28. Epub 2021 Jun 28.

Department of Hemato-oncology, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 142 00, Czech Republic; Childhood Leukaemia Investigation Prague, Department of Pediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague 150 06, Czech Republic. Electronic address:

Hematopoietic stem cell transplantation (HSCT) is a frequent therapeutic approach to restore hematopoiesis in patients with hematologic diseases. Patients receive a hematopoietic stem cell (HSC)-enriched donor cell infusion also containing immune cells, which may have a beneficial effect by eliminating residual neoplastic cells. However, the effect that donor innate immune cells may have on the donor HSCs has not been deeply explored. Read More

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Escalated dose donor lymphocyte infusion treatment in patients with primary immune deficiencies after HSCT with reduced-intensity conditioning regimen.

Hematol Oncol Stem Cell Ther 2021 Jul 2. Epub 2021 Jul 2.

Pediatric Cell and Gene Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective/background: Mixed chimerism (MC) is the allogeneic hematopoietic stem cell transplantation (HSCT) major concern using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor lymphocyte infusion (DLI) escalating dose regimen has been developed with the aim of reducing toxicity while preserving efficacy. However, the graft-versus-host disease (GvHD) development remains the most common and adverse effect of DLI and continues to be a limiting factor in its application, especially nonmalignant diseases such as PIDs. Read More

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Allogeneic hematopoietic stem cell transplantation improves long-term outcome for relapsed AML patients across all ages: results from two East German Study Group Hematology and Oncology (OSHO) trials.

Ann Hematol 2021 Jul 7. Epub 2021 Jul 7.

University Hospital Leipzig, 04106, Leipzig, Germany.

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Read More

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Combination of mesenchymal stem cells and FK506 prolongs heart allograft survival by inhibiting TBK1/IRF3-regulated-IFN-γ production.

Immunol Lett 2021 Jul 4. Epub 2021 Jul 4.

Organ Transplantation institute, School of Medicine, Xiamen University, Xiamen, Fujian, China; Fujian Key Laboratory of Organ and Tissue Regeneration, Xiamen, Fujian, China; Medical College, Guangxi University, Nanning, Guangxi, China. Electronic address:

Lifelong immunosuppression use presents many serious side effects to transplant recipients. Previous studies have shown that mesenchymal stem cells (MSC) regulate the progress of inflammation and protect allograft function. However, the benefits of MSC combined with low-dose tacrolimus (FK506) has not been investigated in heart transplant recipients, and its mechanism deserves further investigation. Read More

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Prophylactic or preemptive low-dose azacitidine and donor lymphocyte infusion to prevent disease relapse following allogeneic transplantation in patients with high risk acute myeloid leukemia or myelodysplastic syndrome.

Transplant Cell Ther 2021 Jul 2. Epub 2021 Jul 2.

Department of Hematology, Nantes University Hospital, Hôtel-Dieu, Nantes, France; Fédération Hospitalo-Universitaire Grand-Ouest Acute Leukemia (FHU GOAL).

Background: Because of the persistently high rates of relapse of patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) following allogeneic stem cell transplantation, maintenance post-transplant therapy has been proposed. We previously initiated a Phase II trial in which epigenetic therapy was combined with immunotherapy in an attempt to reduce disease relapse. In that study, low dose azacitidine (AZA) and escalating dose of donor lymphocyte infusion (DLI) were given as maintenance treatment. Read More

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[Clinical and prognostic values of TP53 mutation in patients with B-lineage acute lymphoblastic leukemia].

Zhonghua Xue Ye Xue Za Zhi 2021 May;42(5):396-401

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China.

To investigate the survival and prognosis of B-lineage acute lymphoblastic leukemia (B-ALL) patients with TP53 mutation. The clinical data of 479 newly diagnosed B-ALL patients treated in the First Affiliated Hospital of Soochow University from January 2016 to December 2019 were retrospectively analyzed. Among 479 B-ALL patients, 34 cases (7. Read More

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[Allogeneic donor-derived CD19 CAR-T therapy of relapsed B-cell acute lmphoblastic leukemia after allogeneic hematopoietic stem cell transplantation].

Zhonghua Xue Ye Xue Za Zhi 2021 May;42(5):383-389

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1. Read More

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Fractionated Infusion of Hematopoietic Progenitor Cells Does Not Improve Neutrophil Recovery or Survival in Allograft Recipients.

Transplant Cell Ther 2021 Jun 30. Epub 2021 Jun 30.

Adult Blood and Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. Electronic address:

Allogeneic hematopoietic cell transplantation (HCT) offers a potentially curative therapy in patients with hematologic malignancies; however, nonrelapse mortality (NRM) remains a concern. Strategies to improve neutrophil recovery and immune reconstitution are needed to decrease NRM. Murine models of allogeneic HCT suggest that fractionated hematopoietic progenitor cell (HPC) infusion may improve engraftment through improved access of HPCs to a viable hematopoietic niche. Read More

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Adjuvant treatment with adipose-derived mesenchymal stem cells (ADSC) reduces severe refractory hemorrhagic cystitis after RIC-PBSCT: A case report.

Medicine (Baltimore) 2021 Jul;100(26):e26316

Hematology Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Institute of Hematology, Urumqi, China.

Introduction: Severe hemorrhagic cystitis (HC) is still a common complication after allogeneic hematopoietic stem cell transplantation, which affects the quality of life of patients, and may even cause kidney failure. This study reports the clinical effect of adjuvant treatment of adipose-derived mesenchymal stem cells (ADSCs) on severe refractory HC after of reduced intensity conditioning haplotype high-dose peripheral blood hematopoietic stem cell transplantation (RIC-PBSCT) in one case.

Patient Concerns: A 53-year-old female patient with acute myeloid leukemia (FLT3-ITD) at high risk received RIC-PBSCT. Read More

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Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia.

Front Med 2021 Jun 25. Epub 2021 Jun 25.

Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, Dalian Key Laboratory of Hematology, Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Diamond Bay Institute of Hematology, the Second Hospital of Dalian Medical University, Dalian, 116027, China.

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Read More

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Continuous nasogastric milk feeding versus intermittent bolus milk feeding for preterm infants less than 1500 grams.

Cochrane Database Syst Rev 2021 06 24;6:CD001819. Epub 2021 Jun 24.

Cochrane Children and Families Network, c/o Cochrane Pregnancy and Childbirth, Department of Women's and Children's Health, The University of Liverpool, Liverpool, UK.

Background: Milk feedings can be given via nasogastric tube either intermittently, typically over 10 to 20 minutes every two or three hours, or continuously, using an infusion pump. Although the theoretical benefits and risks of each method have been proposed, their effects on clinically important outcomes remain uncertain.  OBJECTIVES: To examine the evidence regarding the effectiveness of continuous versus intermittent bolus tube feeding of milk in preterm infants less than 1500 grams. Read More

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Fever supports CD8 effector T cell responses by promoting mitochondrial translation.

Proc Natl Acad Sci U S A 2021 Jun 14;118(25). Epub 2021 Jun 14.

Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg im Breisgau, Germany;

Fever can provide a survival advantage during infection. Metabolic processes are sensitive to environmental conditions, but the effect of fever on T cell metabolism is not well characterized. We show that in activated CD8 T cells, exposure to febrile temperature (39 °C) augmented metabolic activity and T cell effector functions, despite having a limited effect on proliferation or activation marker expression. Read More

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Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model.

Front Immunol 2021 2;12:660900. Epub 2021 Jun 2.

Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC, United States.

Background: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA.

Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Read More

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Pre-transplant donor-type red cell transfusion is a safe and effective strategy to reduce isohemagglutinin titers and prevent donor marrow infusion reactions in major ABO-mismatched transplants.

Ann Hematol 2021 Aug 19;100(8):2071-2078. Epub 2021 Jun 19.

Cure2Children Foundation, Florence, Italy.

ABO incompatibility is not a barrier to allogeneic stem cell transplant but may result in acute hemolytic reactions. As stem cell product manipulation is cumbersome, we are reporting the effectiveness and safety of donor-type red cell infusion as a method of reducing acute hemolytic reaction while using marrow as stem cell source. In major ABO-mismatched bone marrow transplants, manipulation of marrow product requires expertise and expensive equipment, which may not be readily available to transplant centers in low- and middle-income regions. Read More

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Safety and Efficacy of Co-transplantation of Hematopoietic Stem Cells Combined With Human Umbilical Cord-Derived Mesenchymal Stem Cells in Children With Severe Aplastic Anemia: A Single-Center Experience.

Exp Clin Transplant 2021 Jun 17. Epub 2021 Jun 17.

From the Pediatric Hematology and Oncology/Bone Marrow Transplantation Unit, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.

Objectives: The most important problems that limit the effectiveness of allogeneic hematopoietic stem cell transplantation in patients with severe aplastic anemia are graft failure and graft-versus-host disease. Mesenchymal stem cells can support normal hematopoiesis and prevent graft-versus-host disease. We aimed to analyze the effects of combined transplant of human umbilical cord-derived mesenchymal stem cells and matched donor allogeneic hematopoietic stem cells in children with severe aplastic anemia. Read More

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DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy.

Am J Physiol Heart Circ Physiol 2021 Aug 18;321(2):H382-H389. Epub 2021 Jun 18.

Division of Cardiology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. Read More

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IL-7 and IL-15 Levels Reflect the Degree of T Cell Depletion during Lymphopenia and Are Associated with an Expansion of Effector Memory T Cells after Pediatric Hematopoietic Stem Cell Transplantation.

J Immunol 2021 Jun 9. Epub 2021 Jun 9.

Hematopoietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Differentially and functionally distinct T cell subsets are involved in the development of complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about factors regulating their recovery after HSCT. In this study, we investigated associations between immune-regulating cytokines, T cell differentiation, and clinical outcomes. We included 80 children undergoing allogeneic HSCT for acute leukemia using bone marrow or peripheral blood stem cells grafted from a matched sibling or unrelated donor. Read More

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[Research Advance of Autophagy in Acute Intestinal Graft-Versus-Host Disease--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):998-1001

College of Chinese Medicine , Shandong University of Traditional Chinese Medicine; Jinan 250011, Shandong Province, China,E-mail:

Acute intestinal graft-versus-host disease is a refractory disease which can affect implantation and become a threat to life in severe cases. Autophagy is an intracellular degradation pathway necessary for maintaining cellular energy homeostasis. In recent years, a large number of studies have found that it is closely related to the pathogenesis and process of acute intestinal graft-versus-host disease. Read More

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[The Effect of γ-secretase Inhibitor Combined with BMSC on the aGVHD in Mice Model].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Jun;29(3):937-943

Department of Hematology, Taian City Central Hospital, Shandong First Medical University, Taian 271000, Shandong Province, China,E-mail:

Objective: To establish the aGVHD mouse model,and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice.

Methods: C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. Read More

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