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三联干细胞输注可减轻移植物抗宿主病并改善非处理单倍体造血干细胞移植的结局。

Triple stem cell infusion alleviated graft-versus-host disease and improves outcomes in unmanipulated haploidentical hematopoietic stem cell transplantation.

作者信息

Hua Fang, Zhang Shan, Zhang Xiaomei, Deng Yan, Han Ying, Lai Sihan, He Ying, Ma Lei, Zhang Xupai, Chen Dan, Su Yi, Xiao Jian, Zhang Ling, Yang Hui, Huang Rong, Hu Haiyan, Chen Mingli, He Guangcui, Yao Hao, Yi Hai

机构信息

Department of Hematology, The General Hospital of Western Theater Command, Sichuan Clinical Research Center for Hematological Disease, Branch of National Clinical Research Center for Hematological Disease, Chengdu, China.

Department of Hematology, Zigong First People's Hospital, Zigong, China.

出版信息

Cell Transplant. 2025 Jan-Dec;34:9636897251359786. doi: 10.1177/09636897251359786. Epub 2025 Jul 25.

DOI:10.1177/09636897251359786
PMID:40709367
Abstract

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) provides cure opportunity for patients requiring prompt allogeneic HSCT but failing to identify well-matched donor, but its outcomes are potentially impaired by increased transplant-related mortality (TRM). We performed haplo-HSCT using granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood stem cells (PBSCs), umbilical cord mesenchymal stem cells (UC-MSCs) and third-party unrelated umbilical cord blood (UCB) stem cells. Modified "Beijing protocol" were performed in this study. All of the patients were transplanted by Busulfan or TBI-based regimen. Anti-thymocyte globulin were used to T-cell depletion . Cyclosporine, mycophenolate mofetil, and short course methotrexate were used to prevent graft-versus-host disease (GVHD). One hundred and sixty-five patients with hematological disorders undergoing haplo-HSCT from Jan 2021 to Nov 2023 were included in this study. The median time of neutrophil engraftment were 12 days (range: 9-25 days), and the median time of platelet engraftment were 13 days (range: 6-50 days). Full haploidentical donor chimerism were obtained within 30 days. No evidence of UCB chimerism was found. Twenty-five patients developed acute GVHD. The incidence of grade II-IV and grade III-IV acute GVHD was 12.73% and 6.67%, respectively. Twenty-eight patients developed chronic GVHD, 10 were limited (6.06%) and 18 were extensive (10.91%). The TRM is total of 26 deaths (15.8%) and the cumulative incidence of relapse (CIR) is total of 17 deaths (11.8%) occurred as of the statistical period. The 2 years overall survival (OS) rate is 72.96%. The median overall survival rate was not reached. Haplo-HSCT performed by PBSCs, UC-MSCs and UCB "triple-infusion" achieved excellent outcomes, and need to explored in a larger cohort.

摘要

单倍体相合造血干细胞移植(Haplo-HSCT)为那些需要立即进行异基因造血干细胞移植但未能找到完全匹配供体的患者提供了治愈机会,但其结果可能会因移植相关死亡率(TRM)的增加而受到影响。我们使用粒细胞集落刺激因子(G-CSF)动员的外周血干细胞(PBSCs)、脐带间充质干细胞(UC-MSCs)和第三方无关脐带血(UCB)干细胞进行了单倍体相合造血干细胞移植。本研究采用了改良的“北京方案”。所有患者均采用基于白消安或全身照射(TBI)的方案进行移植。使用抗胸腺细胞球蛋白进行T细胞清除。使用环孢素、霉酚酸酯和短疗程甲氨蝶呤预防移植物抗宿主病(GVHD)。本研究纳入了2021年1月至2023年11月期间接受单倍体相合造血干细胞移植的165例血液系统疾病患者。中性粒细胞植入的中位时间为12天(范围:9 - 25天),血小板植入的中位时间为13天(范围:6 - 50天)。在30天内获得了完全的单倍体相合供体嵌合体。未发现脐带血嵌合体的证据。25例患者发生了急性移植物抗宿主病。II-IV级和III-IV级急性移植物抗宿主病的发生率分别为12.73%和6.67%。28例患者发生了慢性移植物抗宿主病,10例为局限性(6.06%),18例为广泛性(10.91%)。截至统计期,移植相关死亡率总计26例死亡(15.8%),复发累积发生率(CIR)总计17例死亡(11.8%)。2年总生存率(OS)为72.96%。中位总生存率未达到。通过外周血干细胞、脐带间充质干细胞和脐带血“三联输注”进行的单倍体相合造血干细胞移植取得了优异的结果,需要在更大的队列中进行探索。

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本文引用的文献

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Increased Epstein‒Barr virus reactivation following prophylaxis for cytomegalovirus infection after haploidentical haematopoietic stem cell transplantation.同种异体造血干细胞移植后预防巨细胞病毒感染引起的 EBV 再激活增加。
J Hematol Oncol. 2024 Oct 12;17(1):94. doi: 10.1186/s13045-024-01612-y.
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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial.单倍体相合造血细胞移植联合或不联合无关脐带血单位治疗成人急性髓系白血病的多中心、随机、开放标签、3 期临床试验。
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Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant: An Open-Label Randomized Clinical Trial.
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Quadruple stem cells transplantation of haploidentical bone marrow and PBSCs supporting by third-party umbilical cord blood and MSCs achieved excellent outcomes.单倍体相合骨髓和外周血干细胞四重干细胞移植,辅以第三方脐带血和间充质干细胞,取得了优异的效果。
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Transplant Cell Ther. 2022 Dec;28(12):849.e1-849.e8. doi: 10.1016/j.jtct.2022.08.025. Epub 2022 Aug 29.
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