Donors with HLA-B*58:01/TNFα − 308A haplotype are unfavorable to haploidentical hematopoietic stem cell transplantation in acute lymphoblastic leukemia

•HLA-B*58:01/TNFα − 308A haplotype was identified in related donors for allo-HSCT.•ALL recipients with these related donors usually had unfavorable prognosis.•Family members carrying this haplotype are unsuitable as haploidentical donors.

We investigated the clinical characteristics of acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) using haploidentical donors carrying HLA-B*58:01/TNFα − 308A (B*58:01-TNF2) haplotype. A total of 136 B-ALL and 29 T/NK-ALL cases were recruited. DNA samples from the patients and their family members were assayed for HLA typing and genotyping of TNFα − 308 (rs1800629). The B*58:01-TNF2 haplotype in related donors was determined by their family relationships. Outcomes within 2 years, disease course, and complications within 100 days were compared among patients using haploidentical donors carrying B*58:01-TNF2 haplotype (21 cases), those using haploidentical donors without B*58:01-TNF2 haplotype (100 cases), and those using HLA-identical sibling donors with or without B*58:01-TNF2 haplotype (44 cases). Compared with the other two groups, patients using haploidentical donors carrying B*58:01-TNF2 haplotype had higher overall mortality (adjusted P = 0.039) and non-relapse mortality (adjusted P = 0.001) within 2 years, delayed platelet engraftment (adjusted P < 0.0001), higher incidences of severe acute graft-versus-host disease (aGVHD) (P = 0.007), severe late-onset hemorrhagic cystitis (P = 0.002), blood stream infection (P = 0.017), and invasive fungal disease (P = 0.004) within 100 days. Therefore, donors carrying the B*58:01-TNF2 haplotype may cause more serious complications and poorer outcomes to ALL recipients.