Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Biol Blood Marrow Transplant. 2013 Nov;19(11):1581-9. doi: 10.1016/j.bbmt.2013.08.003. Epub 2013 Aug 11.
Impaired immunologic recovery (IR) after hematopoietic stem cell transplantation (HSCT) is associated with increased risk for infections and relapse. Stem cell source and graft manipulation influence the kinetics of IR. Partial T cell depletion of peripheral blood stem cell (PBSC) grafts is a novel alternative method of graft manipulation for children. We compared IR in children undergoing HSCT for hematologic malignancies receiving either T cell-depleted (TCD)-PBSCs (n = 55) or umbilical cord blood (UCB) (n = 21) over a 7-year period at a single institution. PBSC grafts underwent ex vivo negative selection for CD3(+) cells using the CliniMACS system with partial T cell add-back. Recovery of CD4(+) T cells was significantly delayed in TCD-PBSC recipients compared with UCB recipients, owing to impaired CD4(+)/CD45RA(+) (naïve) T cell lymphopoiesis. Recovery of total CD3(+) cells and CD3(+)/CD8(+) cells was similar in the 2 groups. The TCD-PBSC recipients had a marked deficit in CD19(+) and, to a lesser extent, IgA/IgM, owing to the need for B cell depletion of these grafts to attenuate the risk of lymphoproliferative disease after TCD HSCT. There were no significant between-group differences in response to mitogen stimulation, time to independence from intravenous immunoglobulin supplementation, or incidence of viral reactivation. Transplantation outcomes of relapse, transplantation-related mortality, event-free survival, and overall survival were similar in the 2 groups. Efforts to enhance IR after partial TCD-PBSC transplantation, such as selective αβ T cell depletion, hold promise for further improvement of this transplantation approach.
造血干细胞移植 (HSCT) 后免疫重建 (IR) 受损与感染和复发风险增加有关。干细胞来源和移植物处理会影响 IR 的动力学。外周血干细胞 (PBSC) 移植物的部分 T 细胞耗竭是儿童移植物处理的一种新的替代方法。我们比较了在单中心进行 HSCT 治疗血液系统恶性肿瘤的儿童中,在 7 年期间接受 T 细胞耗竭 (TCD)-PBSC(n=55)或脐带血 (UCB)(n=21)的 IR。PBSC 移植物在体外使用 CliniMACS 系统进行 CD3(+)细胞的阴性选择,部分 T 细胞回输。由于 CD4(+)/CD45RA(+)(幼稚)T 细胞生成受损,TCD-PBSC 受者的 CD4(+)T 细胞恢复明显延迟,而 UCB 受者则没有。两组患者的总 CD3(+)细胞和 CD3(+)/CD8(+)细胞恢复情况相似。由于需要对这些移植物进行 B 细胞耗竭以减轻 TCD HSCT 后发生淋巴增殖性疾病的风险,TCD-PBSC 受者的 CD19(+)和(程度较轻的)IgA/IgM 显著减少。两组之间在有丝分裂原刺激反应、脱离静脉免疫球蛋白补充的时间、病毒再激活的发生率方面无显著差异。两组的移植结果(复发、移植相关死亡率、无事件生存和总生存)相似。在部分 TCD-PBSC 移植后增强 IR 的努力,如选择性αβ T 细胞耗竭,有望进一步改善这种移植方法。