Prognostic significance of HLA-B leader matching status and its relationship with NK cell reconstitution in patients with hematological malignancies following haploidentical transplantation.

The leader peptide encoded by exon 1 of the HLA-B gene exhibits a dimorphism at position -21. To investigate the influence of HLA-B leader matching status between recipients and donors on the prognosis of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT), as well as potential relevant biological correlates, we conducted a study involving two patient cohorts. Cohort 1 included 1245 patients with hematological malignancies who had complete survival outcome data, while cohort 2 comprised 130 patients who underwent natural killer (NK) cell reconstitution tests post-transplantation. In cohort 1, no significant effect of HLA-B leader matching status on prognosis was found. However, multivariate analysis of a subgroup of patients with myeloid malignancies revealed that HLA-B leader mismatched was associated with significantly higher non-relapse mortality (hazard ratio [HR] = 1.73; P = 0.044), reduced overall survival (HR = 1.67; P = 0.007), and decreased disease-free survival (HR = 1.52; P = 0.015) compared to matched transplants after propensity score matching analysis, findings not observed in lymphoid malignancies. Data from cohort 2 indicated that matched HLA-B leader was associated with favorable NK cell reconstitution in patients with myeloid malignancies. In particular, HLA-B leader matched patients had a higher CD57 expression of total NK and NKG2A+KIR- NK cells, with enhanced NKG2A+KIR- NK cell cytotoxicity (CD107a expression) and IFN-γ secretion at 1, 3, and 6 months post-transplantation (all false discovery rate-adjusted P < 0.05). These findings identify HLA-B leader matching status as a disease-specific prognostic biomarker, suggesting its potential relevance for personalized donor selection considerations in haplo-HSCT settings.