Wide availability of HLA-matched or a few loci-mismatched donors in the graft-vs-host direction among nonsibling first-degree relatives

Although outcomes of hematopoietic stem cell transplantation from alternative donors have been improved, it has not yet challenged the precedence of HLA-matched or a few loci-mismatched donors. Because the availabilities of these donors among nonsibling relatives have been scarcely discussed, we analyzed them using a large Japanese dataset of HLA typing. Data set included HLA data from 2838 patients and their relatives, distributed in all parts of Japan. Antigen mismatches at the HLA-A, -B, -DR loci and allele mismatches at the HLA-A, -B, -C, -DRB1 loci were examined. The availabilities of 0 to 1/6 antigen-mismatched donors among one parent-candidate and one sibling-candidate were 24.3% and 33.9%, and those of 0 to 2/8 allele-mismatched donors were 18.6% and 32.1%, respectively. Additional HLA-C antigen mismatches (18.1% vs 0.0%) along with the possession of 1 to 3/8 allele mismatches (31.3% vs 3.0%) were more frequently observed in parent-candidates than in sibling-candidate. Most multiple allele-mismatched pairs had HLA-B allele mismatches. In conclusion, expanding donor searches to include nonsibling relatives could widen the availability of conventional relative donors with 0 to 1/6 antigen mismatches or 0 to 2/8 allele mismatch to 20% to 30%. High-resolution typing including HLA-C locus examination should be performed, because additional mismatches at HLA-C loci along with multiple allele mismatches were often observed, especially among nonsibling pairs.