Impact of shared HLA determinants between patient and losing cord blood unit on relapse after double cord blood transplantation

• Disease relapse is reduced after DUCBT if the losing unit and the patient share the same HLA mismatch with the winning unit

During double umbilical cord blood transplant (DUCBT), the winning unit (WU) rejects the losing unit (LU) due to WU T-cells directed against the LU mismatched HLA. This immune response might protect against relapse, especially when the patient and LU (PT-LU) share the same mismatch with the WU. To validate this hypothesis, a retrospective Eurocord study, conducted on 383 DUCBT, focused on post-transplant relapse and HLA mismatches between PT-LU and the WU. A PT-LU shared HLA-A mismatch with the WU was associated with a lower 7-year relapse incidence (16% vs. 28%; p=0.048). In addition, multiple PT-LU shared HLA mismatches were also associated with a lower relapse risk (7% vs. 29%; p=0.003). In DUCBT with two or more HLA mismatches between patient and WU, while the number of HLA mismatches between those were not significantly affecting relapse incidence, multiple PT-LU shared HLA mismatches remained associated with a lower relapse risk (7% vs. 29%; p=0.0038). Finally, considering patients who did not develop either grade II-IV acute graft-versus-host disease or chronic graft-versus-host disease, a PT-LU shared HLA-A mismatch as well as multiple PT-LU shared HLA mismatches with the WU remained associated with a significantly lower 7-year relapse incidence. In multivariate adjusted analyses multiple PT-LU shared HLA mismatches remained associated with a significantly reduced 7-year post-transplant relapse risk. Our analysis indicates that, during DUCBT, PT-LU shared HLA mismatches prime an immune response of the WU against leukemia, reducing the long-term risk of post-transplant relapse, and that DCBT has particular utility in those with high-risk leukemia.