Abstract
Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.
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Acknowledgements
We thank all transplantation centers participating in this study, the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire (SFGM-TC), and the Eurocord office. We also thank the personnel from the Etablissement Français du Sang (EFS) for the healthy adult blood samples and the staff at the gynecology and obstetrics department of Pitié-Salpêtrière Hospital (Paris, France) for the cord blood samples. This work was funded by the Institut National du Cancer (AOM06206), the Ministère des Affaires Sociales et de la Santé (DGOS, AOR12106), the Agence de la Biomédecine, the association Laurette Fugain, and the association Capucine.
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Nguyen, S., Achour, A., Souchet, L. et al. Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord. Bone Marrow Transplant 52, 1428–1435 (2017). https://doi.org/10.1038/bmt.2017.122
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DOI: https://doi.org/10.1038/bmt.2017.122
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