Cargando…
Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249182/ https://www.ncbi.nlm.nih.gov/pubmed/28107369 http://dx.doi.org/10.1371/journal.pone.0169512 |
_version_ | 1782497409665859584 |
---|---|
author | Neuchel, Christine Fürst, Daniel Niederwieser, Dietger Bunjes, Donald Tsamadou, Chrysanthi Wulf, Gerald Pfreundschuh, Michael Wagner, Eva Stuhler, Gernot Einsele, Hermann Schrezenmeier, Hubert Mytilineos, Joannis |
author_facet | Neuchel, Christine Fürst, Daniel Niederwieser, Dietger Bunjes, Donald Tsamadou, Chrysanthi Wulf, Gerald Pfreundschuh, Michael Wagner, Eva Stuhler, Gernot Einsele, Hermann Schrezenmeier, Hubert Mytilineos, Joannis |
author_sort | Neuchel, Christine |
collection | PubMed |
description | Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14–1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05–1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01–1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01–1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15–1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91–1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08–0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11–0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13–0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26–5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance. |
format | Online Article Text |
id | pubmed-5249182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52491822017-02-06 Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study Neuchel, Christine Fürst, Daniel Niederwieser, Dietger Bunjes, Donald Tsamadou, Chrysanthi Wulf, Gerald Pfreundschuh, Michael Wagner, Eva Stuhler, Gernot Einsele, Hermann Schrezenmeier, Hubert Mytilineos, Joannis PLoS One Research Article Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14–1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05–1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01–1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01–1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15–1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91–1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08–0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11–0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13–0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26–5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance. Public Library of Science 2017-01-20 /pmc/articles/PMC5249182/ /pubmed/28107369 http://dx.doi.org/10.1371/journal.pone.0169512 Text en © 2017 Neuchel et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Neuchel, Christine Fürst, Daniel Niederwieser, Dietger Bunjes, Donald Tsamadou, Chrysanthi Wulf, Gerald Pfreundschuh, Michael Wagner, Eva Stuhler, Gernot Einsele, Hermann Schrezenmeier, Hubert Mytilineos, Joannis Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title | Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title_full | Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title_fullStr | Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title_full_unstemmed | Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title_short | Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors—A Retrospective Study |
title_sort | impact of donor activating kir genes on hsct outcome in c1-ligand negative myeloid disease patients transplanted with unrelated donors—a retrospective study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249182/ https://www.ncbi.nlm.nih.gov/pubmed/28107369 http://dx.doi.org/10.1371/journal.pone.0169512 |
work_keys_str_mv | AT neuchelchristine impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT furstdaniel impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT niederwieserdietger impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT bunjesdonald impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT tsamadouchrysanthi impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT wulfgerald impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT pfreundschuhmichael impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT wagnereva impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT stuhlergernot impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT einselehermann impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT schrezenmeierhubert impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy AT mytilineosjoannis impactofdonoractivatingkirgenesonhsctoutcomeinc1ligandnegativemyeloiddiseasepatientstransplantedwithunrelateddonorsaretrospectivestudy |