We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.
我们报告了一项随机试验（GITMO，AML-R2）的长期结果，该试验以1:1比例比较了白消安联合环磷酰胺（BuCy2，n=125）与白消安联合氟达拉滨（BuFlu，n=127）作为预处理方案，用于接受异基因造血干细胞移植的急性髓系白血病患者（中位年龄51岁，范围40-65岁）。在中位随访6年后，确认BuFlu受者的非复发死亡率（NRM）显著更优，且这种优势在移植后可持续至4年（10% vs. 20%，p=0.0388）。在年龄大于51岁的患者中，该差异更为明显（BuFlu组11% vs. BuCy2组27%，p=0.0262）。作为全研究人群首要死因的复发累计发生率，在两个随机组间无显著差异。同样，两组的无白血病生存期（LFS）和总生存期（OS）亦无差异，即使按中位年龄分层分析后结果依然一致。BuFlu组与BuCy2组的无移植物抗宿主病-无复发生存期（GRFS）在4年时分别为25% vs. 20%，10年时为20% vs. 17%。因此，NRM降低所带来的生存获益并未被复发增加所抵消。白血病复发仍是主要临床问题，亟待开发新的治疗策略。
肿瘤(癌症)患者之家