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Immune Recovery

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 Transplantation volume 52, pages 1428–1435 (2017)Cite this article

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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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Authors and Affiliations

  1. AP-HP, Hôpital Pitié Salpêtrière (AP-HP), Service d’Hématologie Clinique, Paris, France

    S Nguyen, L Souchet & M Uzunov

  2. Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL8255, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France

    S Nguyen, A Achour, V Béziat & V Vieillard

  3. CHU de Bordeaux Hôpital du Haut-Lévèque, Service d'hématologie clinique et de thérapie cellulaire, Pessac, France

    S Vigouroux

  4. Hematology Department, CHU de Nantes, Nantes, France

    P Chevallier

  5. Institut Paoli Calmettes, Service de greffe de moelle, Marseille, France

    S Furst

  6. Centre Hospitalier Universitaire de Montpellier, Montpellier, France

    A Sirvent

  7. CHU Estaing Service d’Hématologie Clinique, Clermont-Ferrand, France

    J-O Bay

  8. AP-HP, Hôpital Saint-Louis, Service d’Hématologie et de Transplantation, Paris, France

    G Socié

  9. Hôpital Lapeyronie, Montpellier, France

    P Ceballos

  10. CHU de Toulouse, Hématologie Clinique, Toulouse, France

    A Huynh

  11. Institut de Cancérologie de la Loire, Service d’Hématologie, Saint-Priest-en-Jarez, France

    J Cornillon

  12. CHU de Angers, Angers, France

    S Francois

  13. CHU de Nice, Service d’Hématologie, Nice, France

    F Legrand

  14. CHU de Lille, Service d’Hématologie Lille, France

    I Yakoub-Agha

  15. Department of Pediatric Hematology and Oncology, Timone Enfants Hospital and Research Unit EA 3279 Aix-Marseille University, Marseille, France

    G Michel

  16. CHU de Poitiers, Poitiers, France

    N Maillard

  17. CHU Montpellier Pédiatrie, Montpellier, France

    G Margueritte

  18. Hôpital Henri Mondor, Service d'Hématologie, Créteil, France

    S Maury

  19. CHU Grenoble, Grenoble, France

    C-E Bulabois

  20. Hôpital Edouard Herriot, Lyon, France

    M Michallet

  21. University Hospital de Bordeaux, Bordeaux, France

    L Clement

  22. CHU de Rennes, Rennes, France

    C Dauriac

  23. CHRU de Strasbourg, Strasbourg, France

    K Bilger

  24. Department de Bioinformatique et Statistique Médicale, Hôpital Saint-Louis, Paris, France

    J Lejeune & S Chevret

  25. Eurocord Office, Hôpital Saint-Louis, Paris, France

    V Rocha

  26. Hôpital Saint-Antoine, Hématologie Clinique et Thérapie Cellulaire, Paris, France

    B Rio

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  1. S Nguyen
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Correspondence to S Nguyen or V Vieillard.

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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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