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.
在完全匹配供者的减低强度预处理（RIC）造血干细胞移植（HSCT）后，使用移植后环磷酰胺（PTCy）预防移植物抗宿主病（GVHD）的疗效尚未确立。本研究为一项随机、开放标签、多中心的2期临床试验。所有患者均接受氟达拉滨联合2天静脉注射白消安（Flu-Bu2）的RIC方案，并输注来自匹配相关供者或10/10 HLA匹配无关供者的外周血干细胞（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联合标准GVHD预防方案，或在移植后第+3天和第+4天接受PTCy 50 mg/kg/天联合标准GVHD预防方案。主要终点为移植后12个月的GVHD与无复发生存（GRFS）复合终点。共有89例患者被随机分配接受PTCy或ATG对照预防。12个月时，PTCy组无病生存率为65.9%，ATG组为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。12个月时PTCy组GRFS为54.5%，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显著延长。除移植后第+30天时PTCy组的EORTC QLQ-C30评分显著低于ATG组外，两组的生活质量评分随时间变化趋势无差异。虽然未达到主要研究目标，但对于接受Flu-Bu2预处理和完全匹配供者PBSC移植的患者，PTCy能有效预防GVHD，且在不良事件和生活质量方面耐受性良好。本试验已在clinicaltrials.gov注册：NCT02876679。
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