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

During double umbilical cord blood transplant (DUCBT), the winning unit (WU) rejects the losing unit (LU) because of 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 DUCBTs, focused on posttransplant relapse and HLA mismatches between PT-LU and the WU. A PT-LU HLA-A mismatch shared with the WU was associated with a lower 7-year relapse incidence (16% vs 28%; P = .048). In addition, multiple PT-LU shared HLA mismatches were also associated with a lower relapse risk (7% vs 29%; P = .003). In DUCBT with ≥2 HLA mismatches between patient and WU, the number of HLA mismatches between those did not significantly affect relapse incidence, whereas multiple PT-LU shared HLA mismatches remained associated with a lower relapse risk (7% vs 29%; P = .0038). Finally, considering patients who did not develop either grade 2 to 4 acute graft-versus-host disease or chronic graft-versus-host disease, a PT-LU shared HLA-A mismatch as well as multiple PT-LU HLA mismatches shared 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 posttransplant 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 posttransplant relapse, and that DCBT has particular utility in those with high-risk leukemia.