Anti-human leukocyte antigen (HLA) antibodies, particularly donor-specific HLA antibodies (DSA), negatively impact engraftment in hematopoietic cell transplantation. Past studies have proposed various interventions to reduce DSA, but these were primarily from single centers and not from large-scale registry data. Therefore, we conducted a retrospective analysis of nationwide registry data to examine the effects of anti-HLA antibodies on engraftment. Evaluable patients were classified into an anti-HLA antibody-negative group (n = 3657), an anti-HLA antibody-positive group (without high DSA) (n = 137), and a high-DSA (MFI >
5000) group (n = 8). Patient characteristics differed significantly between the anti-HLA antibody-negative and anti-HLA antibody-positive groups, and the number of patients with DSA was lower than expected. Statistical analyses revealed that the anti-HLA antibody-positive group had better neutrophil engraftment than the anti-HLA antibody-negative group (94.0% vs 84.2%, p <
0.001) but worse platelet engraftment (60.3% vs 64.9%, p = 0.047). In the high DSA group, two patients received a DSA-depleting intervention. Only one patient with an MFI of 5832 (without intervention) developed primary graft failure, while the remaining seven achieved engraftment. In this study, the effect of anti-HLA antibodies remained inconclusive, and the possibility of neutrophil engraftment with high-DSA levels was confirmed.