HLA-B leader mismatch predicts increased GVHD risk in haploidentical transplantation: insights from a Latin American cohort

- B-leader mismatch was associated with approximately threefold higher odds of grade III–IV acute GVHD (logistic model). - Findings support including B-leader status in haplo donor selection in Latin America. Polymorphisms in the HLA-B leader sequence have been linked to outcomes after allogeneic hematopoietic stem-cell transplantation (allo-HSCT), particularly in unrelated-donor settings. However, their impact in haploidentical transplantation and in Latin American populations remains unclear. We conducted a retrospective, single-center study of 117 patients who underwent haploidentical HSCT in Chile (2018–2024). Outcomes were analyzed according to HLA mismatches, including HLA-B leader status. Overall survival (OS) was estimated by Kaplan–Meier; acute and chronic GVHD, relapse, and transplant-related mortality were analyzed using cumulative incidence with competing risks. Multivariable models were applied where appropriate. At day 100, the cumulative incidence of grade II–IV acute GVHD was 42% (95% CI, 33–51), with grade III–IV in 24% (95% CI, 16–32). At 1 year, the cumulative incidence of chronic GVHD was 32% (95% CI, 23–41), including mild (19%) and moderate/severe (15%) cases. HLA-B leader mismatch was present in 38% (44/117) and was significantly associated with increased risk of grade III–IV acute GVHD and moderate/severe chronic GVHD (both p<0.01). Patients with HLA-B leader–matched donors had longer mean OS (96.1 vs 56.5 months). OS at 1 year was 83% vs 70% (p=0.04) and at 2 years 69% vs 52% (p=0.03), although the global log-rank comparison was not statistically significant (p=0.206). These findings identify HLA-B leader mismatch as an immunogenetic risk factor in haploidentical HSCT. Incorporating HLA-B leader typing as a secondary donor-selection criterion may help refine donor choice, particularly when multiple related donors are available.