Blood Adv. 2025 May 2:bloodadvances.2025015938. doi: 10.1182/bloodadvances.2025015938. Online ahead of print.
ABSTRACT
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.
PMID:40315369 | DOI:10.1182/bloodadvances.2025015938
