Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide.

Abstract

Little is known regarding the effect of KIR/HLA incompatibilities (inc.) in the setting of T-replete haploidentical allogeneic hematopoietic stem cell transplantation using posttransplant cyclophosphamide (PTCy). In this retrospective study, the impact of KIR/HLA inc. on clinical outcomes and NK cell reconstitution was studied in a cohort of 51 consecutive patients receiving a T cell-replete haploidentical allogeneic hematopoietic stem cell transplantation after a reduced-intensity conditioning using peripheral blood stem cells as the source of the graft and PTCy as graft-versus-host disease (GvHD) prophylaxis. The NK cell repertoire reconstitution was examined by multiparameter flow cytometry in 34 of these 51 patients from day 0 to day 100 posttransplant. Genetic KIR2DL/HLA inc. were found to be significantly associated with more GvHD (81.2 versus 45.7%, p = 0.01) and less relapse (6.2 versus 42.8%, p = 0.008) in this context. GvHD is associated with increased levels of differentiated and activated NK cells. A significant loss of KIR2DL2/3+ NK cells was observed at day 30 in patients with inhibitory KIR/HLA inc., suggesting that responsive KIR NK cells are particularly targeted by the immunosuppressive PTCy treatment. Further investigations are needed from a larger cohort with an identical clinical approach to consolidate these results and to identify the NK cell subsets that may be beneficial for the graft-versus-leukemia effect observed. Because many haploidentical donors can be identified in a family, the prediction of KIR NK cell alloreactivity could be of crucial importance for donor selection and patient outcome.

• Authors: Catherine Willem, Dhon Roméo Makanga, Thierry Guillaume, Bercelin Maniangou, Nolwenn Legrand, Katia Gagne, Pierre Peterlin, Alice Garnier, Marie C Béné, Anne Cesbron, Amandine Le Bourgeois, Patrice Chevallier, Christelle Retière
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 202 Issue 7 Pg. 2141-2152 (04 01 2019) ISSN: 1550-6606 [Electronic] United States
• PMID: 30787107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 by The American Association of Immunologists, Inc.

Chemical References

• HLA Antigens
• Immunosuppressive Agents
• Receptors, KIR
• Cyclophosphamide

Topics

• Adult
• Aged
• Blood Group Incompatibility (immunology)
• Cyclophosphamide (therapeutic use)
• Female
• Graft vs Leukemia Effect (immunology)
• HLA Antigens (genetics)
• Hematopoietic Stem Cell Transplantation (methods)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Killer Cells, Natural (immunology)
• Male
• Middle Aged
• Receptors, KIR (genetics)
• Transplantation, Haploidentical (methods)
• Treatment Outcome