Bryant Adam R, Perales Miguel-Angel
Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA.
Adv Cell Gene Ther. 2019 Jan;2(1). doi: 10.1002/acg2.29. Epub 2018 Dec 4.
Graft-versus-host (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). As donor T cells are recognized as key drivers of GVHD, some approaches to prevent GVHD have focused on T cell depletion of the allograft. In this review we summarize methods and outcomes of T cell depleted (TCD) HCT with a focus on CD34+ selection. This platform is efficacious in preventing acute and chronic GVHD across a wide range of hematologic malignancies, and with the exception of chronic myeloid leukemia, is not associated with adverse relapse or survival outcomes compared to conventional GVHD prophylaxis platforms. In retrospective comparisons recipients of CD34+ selected HCT have higher rates of GVHD-free relapse-free survival (GRFS) than conventional HCT counterparts. Although CD34+ selected allografts require myeloablative and antithymocyte-globulin based conditioning to support engraftment, abrogation of calcineurin inhibitors and methotrexate in this approach reduces its toxicity such that it can be considered in select older and more comorbid patients who could benefit from ablative HCT. A trial comparing GVHD prophylaxis regimens (BMT CTN 1301, NCT02345850) has completed accrual and will be the first to compare CD34+ selected HCT with conventional HCT in a randomized prospective setting. Its findings have potential to establish CD34+ selected HCT as a new standard-of-care platform for GVHD prevention.
移植物抗宿主病（GVHD）是异基因造血细胞移植（HCT）后发病和死亡的重要原因。由于供体T细胞被认为是GVHD的关键驱动因素，一些预防GVHD的方法集中在对移植物进行T细胞清除。在本综述中，我们总结了T细胞清除（TCD）HCT的方法和结果，重点是CD34+选择。该平台在预防广泛的血液系统恶性肿瘤中的急性和慢性GVHD方面有效，并且除慢性粒细胞白血病外，与传统的GVHD预防平台相比，不伴有不良的复发或生存结果。在回顾性比较中，接受CD34+选择的HCT的患者无GVHD无复发生存率（GRFS）高于传统HCT患者。尽管CD34+选择的移植物需要基于清髓和抗胸腺细胞球蛋白的预处理来支持植入，但在这种方法中取消钙调神经磷酸酶抑制剂和甲氨蝶呤可降低其毒性，因此可以考虑用于某些可能从清髓性HCT中获益的老年和合并症更多的患者。一项比较GVHD预防方案的试验（BMT CTN 1301，NCT02345850）已完成入组，将是首个在随机前瞻性研究中比较CD34+选择的HCT与传统HCT的试验。其研究结果有可能将CD34+选择的HCT确立为预防GVHD的新的标准治疗平台。
