The Division of Hematology and Bone Marrow Transplantation, Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Am J Hematol. 2017 Mar;92(3):259-268. doi: 10.1002/ajh.24631. Epub 2017 Feb 1.
Acute graft-versus-host disease (GVHD) is the major treatment-related complication after stem-cell transplantation (SCT) from unrelated-donors. Several GVHD prophylaxis regimens have been explored, but no regimen has shown superiority. We analyzed transplantation outcomes in 472 consecutive unrelated-donor SCT recipients, using cyclosporine/methotrexate (MTX, n = 314) or cyclosporine/mycophenolate-mofetil (MMF, n = 158) for GVHD prophylaxis. Neutrophil engraftment was faster after MMF, days 11 and 14, respectively (P = .001). Acute GVHD grade II-IV and III-IV occurred in 47% and 28% after MMF compared to 27% and 12% after MTX, respectively (P < .001). Nonrelapse mortality (NRM) was 44% and 24%, respectively (P < .001). Death associated with GVHD occurred in 25% and 8% (P < .0001), while other NRM causes occurred in 19% and 16%, respectively (P = .39). Relapse mortality was similar. Overall survival was better after MTX, 40% and 29%, respectively (P = .006). However, this difference had only borderline significance when adjusting for differences in patient characteristics (HR, 1.3, P = .08). To minimize potential selection bias we analyzed outcomes on the basis of an intention-to-treat like analysis. During the years 2008-2009, the leading GVHD prophylaxis regimen for unrelated-donor SCT included MMF (89% of transplants). During the other periods, MTX was used predominantly (82% of transplants). The two periods were otherwise well-matched. Acute GVHD occurred more often in 2008-2009. Death associated with GVHD occurred more often, while other NRM causes occurred less often resulting in similar NRM and overall survival. In conclusion, cyclosporine/MMF is associated with faster engraftment and possibly with less organ toxicity than cyclosporine/MTX. However, it is associated with increased rates of acute GVHD and GVHD-associated deaths.
急性移植物抗宿主病（GVHD）是异基因干细胞移植（SCT）后主要的治疗相关并发症。已经探索了几种 GVHD 预防方案，但没有一种方案显示出优越性。我们分析了 472 例连续接受无关供体 SCT 移植患者的移植结果，其中 314 例采用环孢素/甲氨蝶呤（MTX），158 例采用环孢素/霉酚酸酯（MMF）预防 GVHD。MMF 组的中性粒细胞植入更快，分别在第 11 天和第 14 天（P=0.001）。MMF 组发生 II-IV 级和 III-IV 级急性 GVHD 的比例分别为 47%和 28%，而 MTX 组分别为 27%和 12%（P<0.001）。MMF 组非复发死亡率（NRM）为 44%，MTX 组为 24%（P<0.001）。与 GVHD 相关的死亡分别为 25%和 8%（P<0.0001），而其他 NRM 原因分别为 19%和 16%（P=0.39）。复发死亡率相似。MTX 组的总生存率更好，分别为 40%和 29%（P=0.006）。然而，在调整患者特征差异后，这种差异仅具有边缘显著性（HR，1.3，P=0.08）。为了尽量减少潜在的选择偏倚，我们基于意向治疗分析来分析结果。在 2008-2009 年期间，异基因供体 SCT 的主要 GVHD 预防方案包括 MMF（89%的移植）。在其他时期，主要使用 MTX（82%的移植）。这两个时期的其他方面都很好地匹配。2008-2009 年期间急性 GVHD 更常见。与 GVHD 相关的死亡更常见，而其他 NRM 原因则较少见，导致 NRM 和总生存率相似。总之，环孢素/MMF 与更快的植入速度和可能更少的器官毒性相关，而与更高的急性 GVHD 和与 GVHD 相关的死亡率相关。
