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Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT

Bone Marrow Transplantation volume 56, pages 1900–1907 (2021)Cite this article

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Abstract

Human leukocyte antigen (HLA) class-I mismatches that trigger donor-versus-recipient natural killer (NK)-cell alloreactivity reduce the incidence of leukemia relapse and improve survival of acute myeloid leukemia patients after T-cell-depleted HLA-haplotype mismatched (“haploidentical”) hematopoietic transplantation. In murine graft-versus-host disease (GvHD) models, alloreactive NK-cells also prevent GvHD. Here we report the results of a non-interventional, prospective study performed on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation. The study was aimed at re-assessing the role of NK-cell alloreactivity in a cohort of haploidentical transplants performed in Europe between 2012 and 2015 and composed of unmanipulated, as well as T-cell-depleted transplants. One hundred thirty-eight patients with acute myeloid or lymphoid leukemias were analyzed. Eighty-six patients received ex-vivo T-cell-depleted transplants, 52 patients received unmanipulated transplants. Fifty patients were transplanted from NK alloreactive donors, 88 from non-NK alloreactive donors. NK cell alloreactivity did not impact on GvHD/relapse-free survival (GRFS) in unmanipulated transplants (HR: 1.66 (0.9–3.1), p = 0.1). In contrast, it did impact beneficially on GRFS in T-cell-depleted transplants (HR: 0.6, (0.3–1.2), p = 0.14, interaction p < 0.001). This effect was the consequence of reduced incidences of acute and chronic GvHD and non-relapse mortality.

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Fig. 1: Outcomes according to presence versus absence of donor NK cell alloreactivity in patients who received unmanipulated hematopoietic transplants.
Fig. 2: Outcomes according to presence versus absence of donor NK cell alloreactivity in patients who received T-cell-depleted hematopoietic transplantation.

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Authors and Affiliations

  1. University of Perugia, Perugia, Italy

    Loredana Ruggeri, Mara Merluzzi & Andrea Velardi

  2. Ospedale San Raffaele and Università Vita-Salute San Raffaele, Milano, Italy

    Luca Vago, Fabio Ciceri & Chiara Bonini

  3. EBMT Statistical Unit, Leiden, The Netherlands

    Diderik-Jan Eikema

  4. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

    Liesbeth C. de Wreede

  5. Niño Jesus Children’s Hospital, Madrid, Spain

    Miguel Angel Diaz

  6. IRRCS Ospedale Pediatrico Bambino Gesů, Rome, Italy

    Franco Locatelli

  7. Charles University Hospital, Pilsen, Czech Republic

    Pavel Jindra

  8. Ospedale Ferrarotto, Catania, Italy

    Giuseppe Milone

  9. Hospital Gregorio Marañón, Madrid, Spain

    Josè Luis Diez-Martin

  10. Hospital Universitario Virgen del Rocío, Sevilla, Spain

    Jose Antonio Pérez-Simón

  11. EBMT Data Office Leiden, Leiden, The Netherlands

    Linda Koster, Steffie van der Werf & Anja van Biezen

  12. Hôpital Saint-Louis, APHP, INSERM U1160, Université Paris Diderot, Paris, France

    Antoine Toubert

  13. Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

  14. Institut Paoli-Calmettes, Centre de Lutte Contre le Cancer; Centre d’Investigations Cliniques en Biothérapie, Université d’Aix-Marseille, Inserm CBT, Marseille, France

    Christian Chabannon

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  1. Loredana Ruggeri
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Correspondence to Loredana Ruggeri.

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Ruggeri, L., Vago, L., Eikema, DJ. et al. Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT. Bone Marrow Transplant 56, 1900–1907 (2021). https://doi.org/10.1038/s41409-021-01259-0

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  • DOI: https://doi.org/10.1038/s41409-021-01259-0

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