• Jacek Nowak, Katarzyna Kościńska, Renata Mika-Witkowska, Marta Rogatko-Koroś, Sylwia Mizia, Emilia Jaskuła, Małgorzata Polak, Monika Mordak-Domagała, Janusz Lange, Anna Gronkowska, Wiesław Wiktor Jędrzejczak, Sławomira Kyrcz-Krzemień, Mirosław Markiewicz, Monika Dzierżak-Mietła, Agnieszka Tomaszewska, Barbara Nasiłowska-Adamska, Andrzej Szczepiński, Kazimierz Hałaburda, Andrzej Hellmann, Anna Czyż, Lidia Gil, Mieczysław Komarnicki, Jacek Wachowiak, Małgorzata Barańska, Jerzy Kowalczyk, Katarzyna Drabko, Jolanta Goździk, Barbara Wysoczańska, Katarzyna Bogunia-Kubik, Elżbieta Graczyk-Pol, Agnieszka Witkowska, Anna Marosz-Rudnicka, Klaudia Nestorowicz, Joanna Dziopa, Urszula Szlendak, Krzysztof Warzocha, Andrzej Lange, and Polish Donor-Recipient Matching Study Group.
• Institute of Hematology and Transfusion Medicine, Warsaw, Poland. Electronic address: jnowak@ihit.waw.pl.
• Biol. Blood Marrow Transplant. 2015 May 1; 21 (5): 829-39.

AbstractSome cancers treated with allogeneic hematopoietic stem cell transplantation (HSCT) are sensitive to natural killer cell (NK) reactivity. NK function depends on activating and inhibitory receptors and is modified by NK education/licensing effect and mediated by coexpression of inhibitory killer-cell immunoglobulin-like receptor (KIR) and its corresponding HLA I ligand. We assessed activating KIR (aKIR)-based HLA I-dependent education capacity in donor NKs in 285 patients with hematological malignancies after HSCT from unrelated donors. We found significantly adverse progression-free survival (PFS) and time to progression (TTP) in patients who received transplant from donors with NKs educated by C1:KIR2DS2/3, C2:KIR2DS1, or Bw4:KIR3DS1 pairs (for PFS: hazard ratio [HR], 1.70; P = .0020, Pcorr = .0039; HR, 1.54; P = .020, Pcorr = .039; HR, 1.51; P = .020, Pcorr = .040; and for TTP: HR, 1.82; P = .049, Pcorr = .096; HR, 1.72; P = .096, Pcorr = .18; and HR, 1.65; P = .11, Pcorr = .20, respectively). Reduced PFS and TTP were significantly dependent on the number of aKIR-based education systems in donors (HR, 1.36; P = .00031, Pcorr = .00062; and HR, 1.43; P = .019, Pcorr = .038). Furthermore, the PFS and TTP were strongly adverse in patients with missing HLA ligand cognate with educating aKIR-HLA pair in donor (HR, 3.25; P = .00022, Pcorr = .00045; and HR, 3.82; P = .027, Pcorr = .054). Together, these data suggest important qualitative and quantitative role of donor NK education via aKIR-cognate HLA ligand pairs in the outcome of HSCT. Avoiding the selection of transplant donors with high numbers of aKIR-HLA-based education systems, especially for recipients with missing cognate ligand, is advisable.Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

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