Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
Biol Blood Marrow Transplant. 2012 Dec;18(12):1835-44. doi: 10.1016/j.bbmt.2012.07.003. Epub 2012 Jul 11.
Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT.
单倍体干细胞移植（SCT）通常使用 T 细胞耗竭（TCD）移植物进行；然而，据报道，非复发死亡率（NRM）很高，尤其是在成年患者中。我们假设使用 T 细胞丰富（TCR）移植物，然后进行有效的移植后免疫抑制治疗，将降低 NRM 并改善结果。我们分析了 65 例连续接受 TCR（N = 32）或 TCD（N = 33）单倍体移植的血液系统恶性肿瘤成年患者。所有患者均接受包含马法兰、氟达拉滨和噻替哌的预处理方案。TCR 组接受环磷酰胺（Cy）、他克莫司（Tac）和霉酚酸酯（MMF）的移植后治疗。TCD 组接受抗胸腺细胞球蛋白治疗，然后输注无移植后免疫抑制作用的 CD34+选择细胞。两组大多数患者在移植时均有活动性疾病。分别报告 TCR 和 TCD 受者的结果。植入率分别为 94%和 81%（P = NS）。1 年 NRM 分别为 16%和 42%（P =.02）。移植后 1 年的总生存率（OS）和无进展生存率（PFS）分别为 64%和 30%（P =.02）和 50%和 21%（P =.02）。Ⅱ-Ⅳ级急性移植物抗宿主病（aGVHD）的累积发生率分别为 20%和 11%（P =.20），慢性 GVHD（cGVHD）分别为 7%和 18%（P =.03）。TCR 组观察到 T 细胞亚群的重建更好，感染率更低。这些结果表明，TCR 移植物移植后有效控制 GVHD 可能降低单倍体 SCT 后的 NRM 并改善生存。
