There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT.
在使用不相合无关供者（MMUD）进行异基因干细胞移植（alloSCT）时，移植物抗宿主病（GVHD）和非复发死亡率（NRM）的风险会升高。在欧洲，标准做法是使用兔抗胸腺细胞球蛋白（rATG）来降低MMUD异基因干细胞移植后的高NRM和GVHD风险。作为rATG的替代方案，移植后环磷酰胺（PTCy）在临床中的应用日益增多。由于缺乏来自更大数据集比较证据，目前无法就优先选择哪种方法给出普遍建议。为了完善证据基础，我们在欧洲血液和骨髓移植学会（EBMT）的数据库中，分析了2018年1月至2021年6月期间，接受首次外周血MMUD（9/10抗原匹配）异基因干细胞移植的成年血液恶性肿瘤患者，使用rATG与PTCy预防效果的结果。我们使用Cox比例风险回归模型进行了多变量分析。最终分析共纳入2123名患者（PTCy组，n=583；rATG组，n=1540）。此处报告的p值和风险比（HR）均为多变量分析结果。在异基因干细胞移植后两年，我们发现PTCy组的NRM较低，为18%，而rATG组为24.9%；p=0.028，HR 0.74。PTCy组的总生存率更高，为65.7%，rATG组为55.7%；p<0.001，HR 0.77。PTCy患者的无进展生存率也更好，为59.1%，而使用rATG时为48.8%；p=0.001，HR 0.78。两组间慢性GVHD和急性GVHD的发生率无显著差异。我们发现，与使用rATG相比，接受PTCy的MMUD外周血异基因干细胞移植受者的NRM显著更低，生存率更高。当前分析的结果表明，在MMUD异基因干细胞移植中，PTCy作为GVHD预防手段具有附加价值。
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