Impact of HLA-B leader matching on clinical outcomes of haploidentical hematopoietic stem cell transplantation in adult patients with acute leukemia, a retrospective cohort study

Background: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplant cyclophosphamide (PTCy) has expanded donor availability for acute leukemia, yet the clinical relevance of emerging immunogenetic markers remains uncertain. This study investigated whether donor–recipient human leukocyte antigen (HLA)-B leader matching influences transplantation outcomes in adults with acute leukemia undergoing haplo-HSCT. Methods: This retrospective analytical cohort included consecutive adults (18–65 years) with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who underwent their first haplo-HSCT at one of the most prominent referral hospitals between January 2008 and December 2022. HLA-B leader status was determined by exon 1 sequencing and classified as matched or mismatched between donor and recipient. Outcomes included overall survival (OS), disease-free survival, relapse incidence (RI), non-relapse mortality (NRM), engraftment, acute and chronic graft-versus-host disease (GVHD), and GVHD-free/relapse-free survival (GRFS). Kaplan–Meier methods, Cox regression, and competing-risk models were applied. Results: A total of 140 patients were analyzed (AML 67.9% and ALL 32.1%); 106 (75.7%) were HLA-B leader matched and 34 (24.3%) mismatched, with a median follow-up of 68 months among survivors. HLA-B leader mismatching was not associated with OS [multivariable hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.65–1.60; P = 0.937] or with NRM (HR 1.28; P = 0.34), and rates of acute GVHD (42.5% vs. 50.0%; P = 0.441) and chronic GVHD (25.5% vs. 29.4%; P = 0.65) were comparable between groups. Relapse was numerically lower in the mismatched group (11.8% vs. 24.5%; HR = 0.49, 95% CI: 0.17–1.41; P = 0.184). In multivariable analysis, age 25–40 years (HR = 1.67, 95% CI: 1.04–2.68; P = 0.034) and transplantation in CR2 or beyond (HR = 1.52, 95% CI: 1.01–2.84; P = 0.045) independently predicted inferior OS; acute GVHD was associated with reduced relapse risk (HR = 0.37, 95% CI: 0.16–0.86; P = 0.021). GRFS did not differ significantly by leader status (HR = 0.85; P = 0.47). Conclusion: In adults with acute leukemia undergoing PTCy-based haplo-HSCT, HLA-B leader matching was not associated with survival or GVHD. However, the observed trend toward lower relapse with leader mismatching, together with the protective association between acute GVHD and relapse, suggests a potential graft-versus-leukemia signal that warrants validation in larger cohorts.