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Reduced-intensity conditioning allogeneic stem cell transplantation in malignant lymphoma: current status

Cancer Biology & Medicine 2013年第1期10卷 1-9页

作者： Le Zhang Yi-Zhuo Zhang Department of Hematology Tianjin Medical University Cancer Institute and Hospital Key Laboratory of Cancer Prevention and Therapy Ministry of Education Key Laboratory of Cancer Prevention and therapy Tianjin State Key Laboratory of Breast Cancer Research

stem cell transplantation （allo-SCT） is a potential cure for patients with malignant lymphoma that is based on the graft-versus-lymphoma （GVL） effect. Myeloablative conditioning allo-SCT is associated with high mortality and morbidity, particularly in patients older than 45 years, heavily pretreated patients （prior hematopoietic stem cell transplantation or more than two lines of conventional chemotherapy） or patients affected by other comorbidities. Therefore, conventional allo-SCT is restricted to younger patients （〈50 to 55 years） in good physical condition. Over the last decade, allo-SCT with reduced-intensity conditioning （RIC-allo-SCT） has been increasingly used to treat patients with lymphoma. This treatment is associated with lower toxicity and substantial decrease in the incidence of transplant- related mortality, and has the potential to lead to long-term remissions. Therefore, patients who are not suitable to undergo conventional allo-SCT can benefit from the potentially curative GVL effects of allo-SCT. Although RIC-allo-SCT has improved the survival of lymphoma patients, high post-transplant relapse rates or disease progression mainly results in treatment failure. Thus, further improvement is clearly needed. The role and timing of RIC-allo-SCT in the treatment of lymphoma remains unclear. Therefore, more prospective studies should clarify the effectiveness of this method. In this article, we review the recent literature on RIC-alIo-SCT as a treatment for major lymphoma subtypes. Areas that require further investigation in the context of clinical trials are also highlighted.

关键词： Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (RIC-allo-SCT) Hodgkin's lymphoma indolent lymphoma aggressive lymphoma

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transplant-associated thrombotic microangiopathy:a rare but deadly complication post orthotopic heart transplantation

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Journal of Geriatric Cardiology 2022年第6期19卷 485-486页

作者： Jose Ruiz-Morales Maedeh Ganji Rohan Goswami Division of Advanced Heart Failure&transplant Cardiology Mayo ClinicJacksonvilleFloridaUSA Cardiology Department University of FloridaJacksonvilleFloridaUSA

Thrombotic microangiopathy(TMA)is potentially life-threatening condition caused by small-vessel microthrombi and is associated with schistocyte formation,low platelets and end-organ damage that may not be reversible.[1,2]As a life-threatening condition,TMA recognition in hospitalized patients after organ transplantation is key to improving ***-associated TMA(TATMA)can occur after both solid organ or hematopoietic stem cell transplantation and often mimics other disease processes such as thrombotic throm-bocytopenic purpura(TTP)with similar constellation of symptoms during *** present a rare case of a patient with TATMA after orthotopic heart transplantation.

关键词： thrombotic microangiopathy orthotopic

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hematopoietic stem cell transplantation for Crohn's disease: Gaps, doubts and perspectives

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World Journal of Stem cells 2018年第10期10卷 134-137页

作者： Milton Artur Ruiz Roberto Luiz Kaiser Junior Lilian Piron-Ruiz Tatiana Pena-Arciniegas Priscila Samara Saran Luiz Gustavo De Quadros Bone Marrow transplant Department Associaaao Portuguesa de BeneficenciaSao Joseo Rio PretoSP 15090 470Brazil

Crohn's disease(CD) is an inflammatory bowel disease that can affect any site of the digestive system. It occurs due to an immunological imbalance and is responsible for intestinal mucosal lesions and complications such as fistulas and stenoses. Treatment aims to stabilize the disease, reducing the symptoms and healing intestinal lesions. Surgical procedures are common in patients. cell therapy was initially used to treat this disease in patients who also suffered from lymphoma and leukemia and were considered to be good candidates for autologous and allogeneic transplantation. After transplantation, an improvement was also observed in their CD. In 2003, the procedure began to be used to treat the disease itself, and several case series and randomized studies have been published since then; this approach currently comprises a new option in the treatment of CD. However, considerable doubt along with significant gaps in our knowledge continue to exist in relation to cell therapy for CD. cell therapy is currently restricted to the autologous modality of hematopoietic stem cell transplantation and, experimentally, to mesenchymal stromal cells to directly treat lesions of the anal mucosa. This article presents the supporting claims for transplantation as well as aspects related to the mobilization regime, conditioning and perspectives of cell therapy.

关键词： Stem cell therapy hematopoietic stem cell transplantation Treatment Crohn's disease

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T cell metabolism in graft-versus-host disease

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Blood Science 2020年第1期2卷 16-21页

作者： Yujing Zou Benny J.Chen Division of Hematologic Malignancies and cellular therapy/BMT Duke University Medical CenterDurhamNCUSA

Graft-versus-host disease(GVHD)is a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplant(allo-HSCT),one of the most effective approaches to treat hematopoietic malignancies.1 However,current prophylaxis regimens and treatments that reduce the detrimental effect of acute GVHD can be offset by increased incidence in opportunistic infections and relapse of the primary malignancy.2 In addition,the majority of the approaches that inhibit T cell responses are non-specific,resulting in the inhibition of both alloreactive T cells and protective T cells from the ***,there is an increase in the demand to develop novel approaches that selectively target alloreactive T *** potential means to address this issue is to take advantage of the unique metabolic profile of activated T cells.

关键词： Graft-versus-host-disease Metabolism T cells

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Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

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World Journal of Gastroenterology 2023年第20期29卷 3084-3102页

作者： Hao Wang Zheng-Lu Wang Sai Zhang De-Jun Kong Rui-Ning Yang Lei Cao Jian-Xi Wang Sei Yoshida Zhuo-Lun Song Tao Liu Shun-Li Fan Jia-Shu Ren Jiang-Hong Li Zhong-Yang Shen Hong Zheng The First Central Clinical School Tianjin Medical UniversityTianjin 300190China Department of Organ transplant Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300190China Key Laboratory of transplant Medicine Chinese Academy of Medical SciencesTianjin 300190China School of Medicine Nankai UniversityTianjin 300190China Research Institute of transplant Medicine Nankai UniversityTianjin 300071China Tianjin Key Laboratory for Organ transplantation Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300071China National Health Commission’s Key Laboratory for Critical Care Medicine Tianjin First Central HospitalTianjin 300071China

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical *** previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy ***,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell ***,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after *** To investigate the functions and underlying mechanisms of antirejection effects of metronomic *** A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after *** vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were *** changes in mitochondrial structure were observed using electron *** With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,Pcells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after *** vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous *** also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidati

关键词： Capecitabine Ferroptosis T Lymphocytes Immunosuppressive agents Graft rejection Liver transplantation

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Dynamic monitoring of plasma Epstein-Barr Virus DNA load can predict the occurrence of lymphoproliferative disorders after haploidentical hematopoietic stem cell transplantation

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China Medical Abstracts(Internal Medicine) 2023年第3期40卷 187-187页

作者：陈静 Peking Univ People's Hosp Peking Univ Instit HematolNatl Clin Res CenterHematol DisBeijing Key LabHematopoietic Stem Cell TransplantBeijing 100044

Objective To determine the optimal cutoff value of Epstein-Barr virus(EBV)DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease(PTLD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively *** cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD were determined through constructing the receiver operating characteristic(ROC)curve and calculating the Youden index.

关键词： hematopoietic diagnosis lymphoproliferative

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Generating hematopoietic cells from human pluripotent stem cells:approaches,progress and challenges

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cell Regeneration 2023年第1期12卷 70-90页

作者： Haiqiong Zheng Yijin Chen Qian Luo Jie Zhang Mengmeng Huang Yulin Xu Dawei Huo Wei Shan Ruxiu Tie Meng Zhang Pengxu Qian He Huang Bone Marrow transplantation Center the First Affiliated HospitalZhejiang University School of MedicineZhejiang UniversityHangzhou 310012China Liangzhu Laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou 311121China Institute of Hematology Zhejiang UniversityHangzhou 310012China Zhejiang Province Engineering Laboratory for Stem cell and Immunity therapy Hangzhou 310012China Center for Stem cell and Regenerative Medicine and Bone Marrow transplantation Center of the First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China

Human pluripotent stem cells(hPSCs)have been suggested as a potential source for the production of blood cells for clinical *** two decades,almost all types of blood cells can be successfully generated from hPSCs through various differentiated ***,with a deeper understanding of hematopoiesis,higher efficiency of generating progenitors and precursors of blood cells from hPSCs is ***,how to generate large-scale mature functional cells from hPSCs for clinical use is still *** this review,we summarized recent approaches that generated both hematopoietic stem cells and mature lineage cells from hPSCs,and remarked their efficiency and mechanisms in producing mature functional *** also discussed the major challenges in hPSC-derived products of blood cells and provided some potential *** review summarized efficient,simple,and defined methodologies for developing good manufacturing practice standards for hPSC-derived blood cells,which will facilitate the translation of these products into the clinic.

关键词： Human pluripotent stem cells hematopoietic differentiation hematopoietic stem cells Blood cells

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Clinical analysis of the usefulness of letermovir for prevention of cytomegalovirus infection after haploidentical hematopoietic stem cell transplantation

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China Medical Abstracts(Internal Medicine) 2023年第4期40卷 232-232页

作者：马瑞 Peking Univ People’s Hosp Peking Univ Instit HematolNatl Clin Hematol Dis Res CenterBeijing Key LabHematopoietic Stem Cell TransplantBeijing 100044

Objective To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus(CMV)reactivation in patients receiving haploidentical hematopoietic stem cell *** This retrospective,cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1。

关键词： hematopoietic prevention infection

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Risk factors for bronchiolitis obliterans syndrome in allogeneic hematopoietic stem cell transplantation

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Chinese Medical Journal 2013年第13期126卷 2489-2494页

作者： MO Xiao-dong XU Lan-ping LIU Dai-hong ZHANG Xiao-hui CHEN Huan CHEN Yu-hong HAN Wei WANG Yu WANG Feng-rong WANG Jing-zhi LIU Kai-yan HUANG Xiao-jun Peking University People's Hospital & Institute of Hematology Beijing Key laboratory of Hematopoitic Stem Cell Transplantation Beijing 100044 China

Background The occurrence of bronchiolitis obliterans syndrome （BOS） after allogeneic hematopoietic stem cell transplantation （alIo-HSCT） is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after alIo-HSCT. Methods A nested case-control study was designed. Cases with BOS and controls matched for the year of alIo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent alIo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia. Results Thirty-six patients suffered from BOS; the mean age at the time of presentation was （32.7±2.4） years, and the mean time to presentation was （474±350） days post-HSCT. A pre-HSCT cyclophosphamide dose of 〉3.2 g/m2 （OR=8.74, P=0.025）, chronic graft-versus-host disease （moderate to severe）（OR=12.02, P=0.000）, and conditioning regimens without antithymocyte globulin （OR=2.79, P=0.031） were independently associated with BOS. Conclusions We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after alIo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.

关键词： bronchiolitis obliterans syndrome allogeneic hematopoietic stem cell transplantation graft-versus-host disease,"antithymoeyte globulin

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Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes

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China Medical Abstracts(Internal Medicine) 2023年第3期40卷 186-186页

作者：李子郁 Peking Univ People's Hosp Peking Univ Instit HematolNatl Clin Res CenterHematol DisBeijing Key LabHematopoietic Stem Cell TransplantBeijing 100044

Objective To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and theireffect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia(CP-CML)receiving initial second-generation tyrosine kinase inhibitors(2G-TKI).Methods Data from consecutive patients aged≥18 years with newly diagnosed CP-CML who received initial 2 G-TKI at Peking University People’s Hospital from September 2008 to November 2021 were interrogated.

关键词： patients myeloid treatment

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