Lymphocyte Crossmatch Testing or Donor HLA-DP and -DQ Allele Typing Effectiveness in Single Cord Blood Transplantation for Patients with Anti-HLA antibodies Other Than Against HLA-A, -B, -C, and -DRB1

Background Anti-human leukocyte antigen (HLA) antibodies other than those against HLA-A, -B, -C, and DRB1 are a risk factor for engraftment delay and failure, especially in cord blood transplantation (CBT) Objectives The primary objective of this study was to assess the impact of the presence of anti-HLA antibodies on CBT and to evaluate the utility of lymphocyte crossmatch testing or additional HLA-DP and HLA-DQ typing of CB units in improving transplant outcomes Study Design We retrospectively assessed the engraftment rates and transplant outcomes of 772 patients who underwent their first CBT at our hospital between 2012 and 2021. Donors were routinely typed for HLA-A, -B, -C, and-DRB1 alleles, and the anti-HLA antibodies of recipients were screened before donor selection in all cases. Among patients who had antibodies against other than HLA-A, -B, -C, and DRB1 (n=58), lymphocyte crossmatch testing (n=32) or additional HLA-DP/-DQ alleles typing of CB (n=15) was performed to avoid the use of units with corresponding alleles Results The median patient age was 57 years (16–77). Overall, 75.7% had a high-risk disease status at transplantation, 83.5% received myeloablative conditioning regimens, and > 80% were heavily transfused. Two hundred and twenty-nine of the 772 recipients (29.6%) were positive for anti-HLA antibodies. There were no statistical differences in the number of infused CD34-positive cells between the anti-HLA antibody-positive and the anti-HLA antibody-negative patients. Of the 229 patients with anti-HLA antibodies, 168 (73.3%) had antibodies against HLA-A, -B, -C, and-DRB1 (group A), whereas 58 (25.3%) had antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5 with or without antibodies against HLA-A, -B, C, and-DRB1 (group B). No patients in both group A and B exhibited DSAs against HLA-A, -B, -C, -and DRB1. The neutrophil engraftment rate was lower in patients with anti-HLA antibodies than in those without antibodies (89.9% vs. 94.1%), whereas non-relapse mortality (NRM) before engraftment was higher in antibody-positive patients (9.6% vs. 4.9%). In patients who received two or more HLA allele-mismatched CB in the host-versus-graft (HVG) direction (n = 685), the neutrophil engraftment rate was lower in the anti-HLA antibody-positive recipients than in the antibody-negative recipients with significant differences (88.8% vs. 93.8%) (P = 0.049). Similarly, transplant outcomes were worse in the antibody-positive patients with respect to two-year overall survival (OS) (43.1% vs. 52.3%) and NRM (44.0% vs. 30.7%) than in the antibody-negative patients. In contrast, the results of group B were comparable to those of the antibodies-negative patients, while the results of group A were statistically worse than the antibody-negative patients in terms of all engraftment rate (88.6%), OS (34.2%), and NRM (49.0%) Conclusions The presence of anti-HLA antibodies negatively impacts engraftment, NRM, and OS in CBT. However, HLA-DP/-DQ allele typing of CB units or lymphocyte crossmatch testing could be useful strategies to overcome poor engraftment rates and transplant outcomes, especially in patients with anti-HLA antibodies against HLA-DP, HLA-DQ, or -DRB3/4/5.