Superior outcomes with offspring B-leader-matched haploidentical versus older matched sibling donors in AL/MDS patients aged ≥40 years.

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.