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.

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Publication Details

Journal
Blood Advances
Published
2025-05-02
DOI
https://doi.org/10.1182/bloodadvances.2025015938
Citations
4
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
7.08
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article

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

Anna Castleton, Vanderson Rocha, Nicolaas PM Schaap, Philippe Guardiola et al.
4 citations
Blood Advances
Hematopoietic Stem Cell Transplantation
7.08
article

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

Anna Castleton, Vanderson Rocha, Nicolaas PM Schaap, Philippe Guardiola, Ryad Tamouza, Srividhya Senthil, Chloe Anthias, Fernanda Volt, Chantal Kenzey, Katherine Clesham, Jan J. Cornelissen, Graziana Maria Scigliuolo, Barbara Cappelli, Persis Amrolia, Robert Wynn, Annalisa Ruggeri, Régis Peffault de Latour, Marc Bierings, Kay Poulton, E Gluckman
article en
4 citations

Abstract

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.

Blood AdvancesVol. 9(17)
European Organisation for Rare Diseases (FR), University College London Hospitals NHS Foundation Trust (GB), Radboud University Nijmegen (NL), Inserm (FR), Universidade de São Paulo (BR), Université Paris-Est Créteil (FR), Université Paris Cité (FR), Great Ormond Street Hospital (GB), Great Ormond Street Hospital for Children NHS Foundation Trust (GB), The Royal Free Hospital (GB), Manchester Royal Infirmary (GB), Erasmus MC (NL), Radboud University Medical Center (NL), San Raffaele University of Rome (IT), Manchester University NHS Foundation Trust (GB), Royal Marsden Hospital (GB), Princess Máxima Center (NL), The Christie Hospital (GB), The Christie NHS Foundation Trust (GB), Scientific Centre of Monaco (MC), Hôpital Saint-Louis (FR), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Erasmus MC Cancer Institute (NL), Royal Manchester Children's Hospital (GB), University College London (GB), Université d'Angers (FR)
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Hematopoietic Stem Cell Transplantation
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