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Prediction of NK Cell Licensing Level in Selection of Hematopoietic Stem Cell Donor, Initial Results

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Natural killer (NK) cell licensing status depends on clonal expression of inhibitory killer cell immunoglobulin-like receptors (iKIR) and short term HLA environment. Licensed NK cells are more efficient in tumor killing than unlicensed NK cells. Cognate KIR–HLA pairs in hematopoietic stem cell transplant (HSCT) donor and recipient are decisive for the possible change in the NK cell licensing status after HSCT. We assessed clinical outcomes in 297 patients with lymphoproliferative or myeloproliferative malignancies, or myelodysplastic syndrome in a model with upward licensing, downward resetting, and unchanged licensing genetics status after T cell replate HSCT from unrelated donors. We found extremely low (0%) relapse/progression incidence (RI), and better (59%) event-free survival (EFS) in recipients with upward licensing status and highly increased RI (37.5%), and reduced EFS (8%) among patients with the downward resetting status of repopulated donor NK cells after HSCT, as compared with unchanged NK cell licensing (RI 23%, EFS 47%). These trends were confirmed in adjusted multivariable models (for RI p = 6.66E−09, OR = 1.47, 95% CI 1.29–1.66 and for EFS p = 3.79E−13, OR = 1.67, 95% CI 1.50–1.84). Differences in the incidence of acute graft versus host disease (GvHD 62, 69, and 47%) and chronic GvHD (24, 44, and 15%, respectively) in three groups were insignificant. It would be rationale the preferential selection of the donors with upward licensing over downward resetting inhibitory KIR:HLA constellation and inclusion of the KIR genotyping in the donor selection algorithm for malignant patients. Further studies using enlarged cohorts of patients with more homogenous diagnosis are essential to reliably verify these preliminary data.

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Acknowledgements

The authors would like to thank the following members of Polish Donor–Recipient Matching Study Group who have provided clinical data: Monika Mordak-Domagała and Janusz Lange, from Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wroclaw, Jacek Wachowiak and Małgorzata Barańska from Department of Oncology Hematology and Pediatrics Transplantology, Poznan Medical University, Poznan, Mieczysław Komarnicki, Lidia Gil and Anna Czyż from Department of Hematology and Bone Marrow Transplantation, Poznan Medical University, Poznan, Anna Gronkowska and Wiesław Wiktor Jędrzejczak from Department of Hematology, Oncology and Internal Medicine, Medical University of Warsaw, Warsaw, Sławomira Kyrcz-Krzemień, Mirosław Markiewicz, Monika Dzierżak-Mietła from Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Katowice, Andrzej Hellmann and Maria Bieniaszewska from Department of Hematology and Transplantology, Medical University of Gdansk, Jerzy Kowalczyk and Katarzyna Drabko from Department of Pediatric Hematology, Oncology and Transplantology, Medical University, Lublin, Jolanta Goździk from Transplantation Centre, University Children’s Hospital, Medical College, Jagiellonian University, Cracow, Kazimierz Hałaburda, Agnieszka Tomaszewska, Barbara Nasiłowska and Andrzej Szczepiński from Department of Hematopoietic Stem Cell Transplantation, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. This study was supported by Grants from the National Center of Science (N N402 351138) and the National Centre for Research and Development (N R13 0082 06).

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Authors and Affiliations

  1. Institute of Hematology and Transfusion Medicine, Indira Gandhi 14, 02-776, Warsaw, Poland

    Marta Rogatko-Koroś, Renata Mika-Witkowska, Klaudia Nestorowicz, Joanna Dziopa, Urszula Szlendak, Sławomir Gwozdowicz, Elżbieta Graczyk-Pol & Jacek Nowak

  2. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland

    Katarzyna Bogunia-Kubik, Barbara Wysoczańska, Emilia Jaskuła & Andrzej Lange

  3. Lower Silesian Center for Cellular Transplantation with National Bone Marrow Donor Registry, Wrocław, Poland

    Emilia Jaskuła, Katarzyna Kościńska & Andrzej Lange

Authors
  1. Marta Rogatko-Koroś
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  2. Renata Mika-Witkowska
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  3. Katarzyna Bogunia-Kubik
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  4. Barbara Wysoczańska
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  6. Katarzyna Kościńska
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  7. Klaudia Nestorowicz
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  9. Urszula Szlendak
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  11. Elżbieta Graczyk-Pol
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  12. Andrzej Lange
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  13. Jacek Nowak
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Correspondence to Jacek Nowak.

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Rogatko-Koroś, M., Mika-Witkowska, R., Bogunia-Kubik, K. et al. Prediction of NK Cell Licensing Level in Selection of Hematopoietic Stem Cell Donor, Initial Results. Arch. Immunol. Ther. Exp. 64 (Suppl 1), 63–71 (2016). https://doi.org/10.1007/s00005-016-0438-2

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  • DOI: https://doi.org/10.1007/s00005-016-0438-2

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