[Implications of HLA in allogeneic stem cell transplantation]

Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic stem cell transplantation. Therefore, the identification of an alternative donor with a lower risk of GVHD is important for patients lacking an HLA-identical sibling donor. To date, HLA studies of large cohorts of unrelated hematopoietic stem cell transplantation (UR-HSCT) have provided important and helpful information for donor selection. In UR-HSCT through Japan Marrow Donor Program, patient and donor HLA-A, -B, and -C, and HLA-DRB1 and -DQB1 double mismatches are significant risk factors for severe GVHD and mortality. HLA-DPB1 mismatch does not affect survival; however, it reduces the chances of leukemia relapse. In the analysis of a specific allele effect on transplant outcomes, HLA-C^*14:02 was significantly associated with an increased risk of severe acute GVHD. The development of next-generation sequencing (NGS) has enabled full-length HLA allele typing. Evolutionary analysis of the entire HLA-DPB1 revealed that a highly conserved region from exon 3 to 3'UTR provoked acute GVHD that was different from a T-cell epitope mismatching algorithm, reflecting exon 2 polymorphisms. Furthermore, a recent study demonstrated the importance of full-length NGS HLA typing on UR-HSCT outcomes. The usage of NGS may provide important information on the implications of the HLA genes in allogeneic stem cell transplantation.