Yujun Wei, Jingwen Tang, Ruoling Yang, Yangliu Shao, Songhua Luan, Lu Wang, Lili Wang, Fei Li, Yongli Wu, Kun Qian, Bo Peng, Haoyang Zhang, Dongxue Ge, Yu Fang, Liuqing Huang, Qingyang Liu, Liping Dou, Daihong Liu
In AL/MDS patients aged ≥40 years, offspring haploidentical B-leader-matched donors were associated with favorable survival outcomes compared with older MSDs, primarily driven by reduced NRM; additionally, DRB1 mismatching was independently associated with reduced relapse.
INTRODUCTION: With advancing safety profiles in allogeneic hematopoietic stem cell transplantation (allo-HSCT), determining whether HLA-matched siblings remain the optimal donor choice for older adults (≥40 years) and whether haploidentical-HSCT demonstrates superior survival outcomes have become pivotal focuses in transplantation research.
METHODS: The goal of this study was to explore the efficacy of haploidentical or matched sibling allo-HSCT in patients over the age of 40 years with acute leukemia (AL) and myelodysplastic syndrome (MDS), with a prespecified primary endpoint of GVHD-free, relapse-free survival (GRFS). In this retrospective study, 195 consecutive AL/MDS patients (≥40 years) who received allo-HSCT between December 2014 and December 2023 were included and analyzed using a 1:2 matched-pair design. All patients received antithymocyte globulin (ATG)-based GVHD prophylaxis. The cohort comprised 130 patients with haploidentical donors (HIDs) and 65 with HLA-matched sibling donors (MSDs).
RESULTS: Patients who received transplants from offspring haploidentical donors with mismatched DRB1 exhibited a significantly lower 5-year cumulative incidence of relapse (15.4%) than those who received MSDs-HSCT (45.3%) or transplants from offspring haploidentical DRB1-matched donors (26.7%; p < 0.001). However, the 5-year nonrelapse mortality (NRM) was highest in the offspring haploidentical B-leader-mismatched group (43.8%) compared with that in the B-leader-matched group (15.4%) and MSDs group (6.3%). Accordingly, in univariate analysis, recipients of offspring haploidentical B-leader-matched donors exhibited superior OS and DFS compared with recipients of older MSDs or offspring B-leader-mismatched donors; multivariate analysis further identified B-leader matching as an independent protective factor against NRM and an independent factor associated with improved GRFS.
CONCLUSION: In AL/MDS patients aged ≥40 years, offspring haploidentical B-leader-matched donors were associated with favorable survival outcomes compared with older MSDs, primarily driven by reduced NRM; additionally, DRB1 mismatching was independently associated with reduced relapse.