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.

Chaim Sheba Medical Center Tel Hashomer Israel

Charles University Hospital Pilsen Czech Republic

Department of Biomedical Data Sciences Leiden University Medical Center Leiden The Netherlands

EBMT Data Office Leiden Leiden The Netherlands

EBMT Statistical Unit Leiden The Netherlands

Hôpital Saint Louis APHP INSERM U1160 Université Paris Diderot Paris France

Hospital Gregorio Marañón Madrid Spain

Hospital Universitario Virgen del Rocío Sevilla Spain

Institut Paoli Calmettes Centre de Lutte Contre le Cancer; Centre d'Investigations Cliniques en Biothérapie Université d'Aix Marseille Inserm CBT Marseille France

IRRCS Ospedale Pediatrico Bambino Gesů Rome Italy

Niño Jesus Children's Hospital Madrid Spain

Ospedale Ferrarotto Catania Italy

Ospedale San Raffaele and Università Vita Salute San Raffaele Milano Italy

University of Perugia Perugia Italy

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