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.