Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naive T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201
Improved Survival After Transplantation of More Donor Plasmacytoid Dendritic or Naive T Cells From Unrelated-Donor Marrow Grafts: Results From BMTCTN 0201
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DOI：
10.1200/jco.2013.54.4577
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发表时间：
2014-08-01
影响因子：
45.3
通讯作者：
Anasetti, Claudio
中科院分区：
文献类型：
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作者：
Waller, Edmund K.;Logan, Brent R.;Anasetti, Claudio
目的探讨非血缘关系供者骨髓(BM)或粒细胞集落刺激因子动员的外周血(PB)干细胞中特异性免疫细胞亚群与BMTCTN 0201移植患者临床结局的关系。在多变量分析中，骨髓移植中浆细胞样树突状细胞(PDCs)和初始T细胞(TNS)的数量与OS独立相关，包括受者和供者的特征，如人类白细胞抗原不匹配、年龄和抗胸腺细胞球蛋白的使用。接受>；pDC、CD8(+)T细胞(CD8Tns)或CD4(+)T细胞(CD4Tns)的骨髓受者的3年OS较好(pDC，56%vs35%；P=.025；CD8Tns，56%vs37%；P=0.012；CD4Tns，55%vs37%；P=.009)。移植更多的骨髓TN与较少的3-4级急性移植物抗宿主病相关，但复发率相似。移植更多的BM pDC与GvHD或移植物排斥反应引起的死亡相关。对外周血移植的分析没有发现与OS、复发或GvHD显著相关的供者细胞亚群。结论骨髓中的供者免疫细胞与非亲缘异基因造血干细胞移植后的存活率有关，但与外周血干细胞移植的存活率无关。异基因移植中供者免疫细胞的生物学活性因移植物来源不同而不同。在异基因造血干细胞移植中，含有更多骨髓来源的TNS和PDCs的供者移植物有利于调节移植后的免疫。(C)美国临床肿瘤学会2014年
PurposeTo characterize relationships between specific immune cell subsets in bone marrow (BM) or granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells collected from unrelated donors and clinical outcomes of patients undergoing transplantation in BMTCTN 0201.Patients and MethodsFresh aliquots of 161 BM and 147 PB stem-cell allografts from North American donors randomly assigned to donate BM or PB stem cells and numbers of transplanted cells were correlated with overall survival (OS), relapse, and graft-versus-host disease (GvHD).ResultsPatients with evaluable grafts were similar to all BMTCTN 0201 patients. The numbers of plasmacytoid dendritic cells (pDCs) and naive T cells (Tns) in BM allografts were independently associated with OS in multivariable analyses including recipient and donor characteristics, such as human leukocyte antigen mismatch, age, and use of antithymocyte globulin. BM recipients of > median number of pDCs, naive CD8(+) T cells (CD8Tns), or naive CD4(+) T cells (CD4Tns) had better 3-year OS (pDCs, 56% v 35%; P = .025; CD8Tns, 56% v 37%; P = .012; CD4Tns, 55% v 37%; P = .009). Transplantation of more BM Tns was associated with less grade 3 to 4 acute GvHD but similar rates of relapse. Transplantation of more BM pDCs was associated with fewer deaths resulting from GvHD or from graft rejection. Analysis of PB grafts did not identify a donor cell subset significantly associated with OS, relapse, or GvHD.ConclusionDonor immune cells in BM but not PB stem-cell grafts were associated with survival after unrelated-donor allogeneic hematopoietic stem-cell transplantation. The biologic activity of donor immune cells in allogeneic transplantation varied between graft sources. Donor grafts with more BM-derived Tns and pDCs favorably regulated post-transplantation immunity in allogeneic hematopoietic stem-cell transplantation. (C) 2014 by American Society of Clinical Oncology