Prophylaxis strategies for Graft versus host disease (GVHD) in allogeneic hematopoietic cell transplantation (allo-HCT) frequently encompass a combination of a calcineurin inhibitor (CNI) with either methotrexate (MTX) or mycophenolate mofetil (MMF). The aim of this retrospective, EBMT registry-based study was to determine outcome differences for chronic myeloid malignancies and secondary acute myeloid leukemia (sAML) between MTX- and MMF-based prophylaxis regimens while taking potential heterogeneity between subgroups into consideration. Eligible were patients transplanted between 2007 and 2017 who received either MTX- or MMF prophylaxis in combination with a CNI. Endpoints after allo-HCT were overall survival, relapse-free survival (RFS), relapse incidence, non-relapse mortality (NRM), and Grades 2–4 acute GVHD (aGvHD). Overall, 13 699 patients from 321 centers were included. Median follow-up was 42.8 months (IQR 19.8–74.5 months). MTX prophylaxis was associated with reduced overall mortality (HR 0.87, 95% CI 0.81–0.95, p = 0.001) and NRM (HR 0.86, 95% CI 0.78–0.96, p = 0.006) compared with MMF in multivariable Cox regression models in the whole cohort without significant interaction between prophylaxis and subgroups. In contrast, there was no significant association of prophylaxis with risk of relapse (HR 1.03 MTX vs. MMF, 95% CI 0.94–1.14, p = 0.53) or RFS (HR 0.95, 95% CI 0.88–1.01, p = 0.12). There was a reduced risk of Grades 2–4 acute GVHD and reduced mortality after acute GVHD with MTX prophylaxis but no association with outcome in a landmark analysis in patients without aGvHD at 3 months after allo-HCT. In conclusion, MTX-complemented CNI prophylaxis was associated with favorable survival, and with favorable survival after aGVHD compared with MMF.

中文翻译：

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甲氨蝶呤与吗替麦考酚酯预防慢性髓系恶性肿瘤的同种异体造血细胞移植：代表 EBMT 慢性恶性肿瘤工作组的回顾性分析


同种异体造血细胞移植 （allo-HCT） 中移植物抗宿主病 （GVHD） 的预防策略通常包括钙调磷酸酶抑制剂 （CNI） 与甲氨蝶呤 （MTX） 或吗替麦考酚酯 （MMF） 的组合。这项基于 EBMT 登记的回顾性研究的目的是确定基于 MTX 和 MMF 的预防方案之间慢性髓系恶性肿瘤和继发性急性髓系白血病 （sAML） 的结果差异，同时考虑亚组之间的潜在异质性。符合条件的患者是 2007 年至 2017 年间接受 MTX 或 MMF 预防联合 CNI 的患者。allo-HCT 后的终点是总生存期、无复发生存期 （RFS） 、复发发生率、非复发死亡率 （NRM） 和 2-4 级急性 GVHD （aGvHD）。共纳入来自 321 个中心的 13 699 例患者。中位随访时间为 42.8 个月 （IQR 19.8-74.5 个月）。在整个队列的多变量 Cox 回归模型中，与 MMF 相比，MTX 预防与总死亡率 （HR 0.87,95% CI 0.81-0.95，p = 0.001） 和 NRM （HR 0.86,95% CI 0.78-0.96，p = 0.006） 相关预防和亚组之间没有显着交互。 相比之下，预防与复发风险 （HR 1.03 MTX vs. MMF，95% CI 0.94-1.14，p = 0.53） 或 RFS （HR 0.95,95% CI 0.88-1.01，p = 0.12） 没有显著关联。 在allo-HCT后3个月，无aGvHD患者的标志性分析显示，预防MTX后发生2-4级急性GVHD的风险降低，死亡率降低，但与结局无关。 总之，与 MMF 相比，MTX 互补的 CNI 预防与良好的生存率相关，并且与 aGVHD 后的良好生存率相关。