The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is not established after reduced intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT) from fully matched donors. This was a randomized, open-label, multicenter, phase 2 trial. All patients received a RIC regimen with fludarabine, intravenous busulfan for 2 days (Flu-Bu2), and a peripheral blood stem cell (PBSC) graft from a matched related or 10/10 HLA-matched unrelated donor. Patients were randomly assigned to receive anti-thymocyte globulin (ATG) 5 mg/kg plus standard GVHD prophylaxis or PTCy 50 mg/kg/d at days +3 and +4 plus standard GVHD prophylaxis. The primary endpoint was the composite endpoint of GVHD- and relapse-free survival (GRFS) at 12 months after HSCT. Eighty-nine patients were randomly assigned to receive either PTCy or control prophylaxis with ATG. At 12 months, disease-free survival was 65.9% in the PTCy group and 67.6% in the ATG group (P = 0.99). Cumulative incidence of relapse, non-relapse mortality, and overall survival were also comparable in the two groups. GRFS at 12 months was 54.5% in the PTCy group versus 43.2% in the ATG group (P = 0.27). The median time to neutrophil and platelet count recovery was significantly longer in the PTCy group compared to the ATG group. Except for day +30, where EORTC QLQ-C30 scores were significantly lower in the PTCy compared to the ATG group, the evolution with time was not different between the two groups. Although the primary objective was not met, PTCy is effective for GVHD prophylaxis in patients receiving Flu-Bu2 conditioning with a PBSC graft from a fully matched donor and was well tolerated in term of adverse events and quality of life. This trial was registered at clinicaltrials.gov: NCT02876679.

在完全匹配的供体进行降低强度调节（RIC）造血干细胞移植（HSCT）后，尚未建立使用移植后环磷酰胺（PTCy）预防移植物抗宿主病（GVHD）的方法。这是一项随机、开放标签、多中心、2 期试验。所有患者均接受 RIC 方案，包括氟达拉滨、静脉注射白消安 2 天 (Flu-Bu2)，以及来自匹配的相关或 10/10 HLA 匹配的无关供体的外周血干细胞 (PBSC) 移植物。患者被随机分配接受抗胸腺细胞球蛋白 (ATG) 5 mg/kg 加标准 GVHD 预防，或在第 +3 天和 +4 天接受 PTCy 50 mg/kg/d 加标准 GVHD 预防。主要终点是 HSCT 后 12 个月的 GVHD 和无复发生存 (GRFS) 的复合终点。89 名患者被随机分配接受 PTCy 或 ATG 对照预防。12 个月时，PTCy 组的无病生存率为 65.9%，ATG 组的无病生存率为 67.6%（P  = 0.99）。两组的累积复发率、非复发死亡率和总生存率也相当。PTCy 组 12 个月时的 GRFS 为 54.5%，而 ATG 组为 43.2%（P  = 0.27）。与 ATG 组相比，PTCy 组中性粒细胞和血小板计数恢复的中位时间明显更长。除了+30天外，PTCy组的EORTC QLQ-C30评分显着低于ATG组，两组之间随时间的演变没有差异。尽管未达到主要目标，但对于接受来自完全匹配供体的 PBSC 移植物的 Flu-Bu2 调节的患者，PTCy 对于 GVHD 预防是有效的，并且在不良事件和生活质量方面具有良好的耐受性。该试验在 ClinicalTrials.gov 上注册：NCT02876679。