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Clinical application of induced pluripotent stem cells (iPS) in autologous settings has just begun. To overcome the high time and cost barriers in the individual production of autologous iPS, the use of allogeneic iPS with a homozygous human leukocyte antigen (HLA) haplotype (HLA‐homo HP) has been proposed. Cord blood transplantation (CBT) is a suitable model for evaluating the allogeneic immunogenicity of iPS transplantation from HLA‐homo donors. We analyzed 1,374 Japanese single cord blood transplant pairs who were retrospectively typed as HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, and ‐DPB1. Among these, six pairs with donor HLA homo—patient‐HLA hetero (homo‐hetero) were found, all of which showed favorable neutrophil engraftment. Multivariate analysis revealed a significantly elevated engraftment risk (HR = 1.59) compared with hetero‐hetero pairs with HLA 1‐2 locus mismatch (789 pts) and comparative risk (HR = 1.23) compared with hetero‐hetero pairs with 0 mismatch (104 pts). These results for CBT with HLA‐homo HP cord blood carry an important implication, namely the possibility that HLA‐homo iPS transplantation results in favorable engraftment. Furthermore, we obtained detailed information on HLA alleles and haplotypes of HLA‐homo. All donor HLA‐homo HPs had a common specific ethnicity and high conservation of the HLA region, and one of two patient heterogeneous HPs invariably shared the same HP as donor HLA‐homo HP, and another non‐shared patient HP was mismatched with 1 to 4 HLA alleles of HLA‐A, ‐B, ‐C, and ‐DRB1 loci in the GVH direction. These findings indicate that patients possessing a single common HLA haplotype have a higher chance of yielding HLA‐homo iPS. S tem  C ells  T ranslational  M edicine   2018;7:173–179

Risk of HLA Homozygous Cord Blood Transplantation: Implications for Induced Pluripotent Stem Cell Banking and Transplantation