Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies
Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies
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DOI：
10.1182/blood-2011-01-332007
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发表时间：
2011-06-23
期刊：
影响因子：
20.3
通讯作者：
Eapen, Mary
中科院分区：
文献类型：
--
作者：
Soiffer, Robert J.;LeRademacher, Jennifer;Eapen, Mary
降低强度预处理（RIC）移植的成功在很大程度上取决于同种免疫效应。关键在于确定抗T细胞抗体输注的免疫调节是否消除了移植的治疗益处。我们检查了1676例接受RIC移植治疗恶性血液病的成人。所有患者均接受烷化剂加氟达拉滨治疗; 792例接受来自人类白细胞抗原匹配同胞的同种异体移植，884例来自8例HLA匹配的无关供体中的7或8例。使用考克斯回归，将体内T细胞去除（n = 584抗胸腺细胞球蛋白[ATG]; n = 213阿来组单抗）后的结果与T细胞充足（n = 879）移植进行比较。Alemtuzumab组2 - 4级急性GVHD发生率低于ATG或T细胞充足方案组（19% vs 38% vs 40%，P < .0001），慢性GVHD发生率低于ATG和ATG方案组（24% vs 40% vs 52%，P < .0001）。然而，与T细胞充满方案相比，Alemtuzumab和ATG的复发率更高（分别为49%，51%和38%，P <0.001）。Alemtuzumab和ATG的无病生存率低于T细胞充足方案（分别为30%、25%和39%，P <0.001）。相应的总生存概率分别为50%、38%和46%（P = 0.008）。这些数据表明，在常规使用RIC方案去除体内T细胞时应采取谨慎的方法。（血。2011;117（25）：6963-6970）
The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti-T-cell antibody infusion abrogates the therapeutic benefits of transplantation. We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 anti-thymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell-replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell-replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell-replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell-replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens. (Blood. 2011;117(25):6963-6970)