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HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rat...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712639/ https://www.ncbi.nlm.nih.gov/pubmed/34970261 http://dx.doi.org/10.3389/fimmu.2021.771449 |
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author | Tsamadou, Chrysanthi Engelhardt, Daphne Platzbecker, Uwe Sala, Elisa Valerius, Thomas Wagner-Drouet, Eva Wulf, Gerald Kröger, Nicolaus Murawski, Niels Einsele, Hermann Schaefer-Eckart, Kerstin Freitag, Sebastian Casper, Jochen Kaufmann, Martin Dürholt, Mareike Hertenstein, Bernd Klein, Stefan Ringhoffer, Mark Frank, Sandra Neuchel, Christine Schrezenmeier, Hubert Mytilineos, Joannis Fuerst, Daniel |
author_facet | Tsamadou, Chrysanthi Engelhardt, Daphne Platzbecker, Uwe Sala, Elisa Valerius, Thomas Wagner-Drouet, Eva Wulf, Gerald Kröger, Nicolaus Murawski, Niels Einsele, Hermann Schaefer-Eckart, Kerstin Freitag, Sebastian Casper, Jochen Kaufmann, Martin Dürholt, Mareike Hertenstein, Bernd Klein, Stefan Ringhoffer, Mark Frank, Sandra Neuchel, Christine Schrezenmeier, Hubert Mytilineos, Joannis Fuerst, Daniel |
author_sort | Tsamadou, Chrysanthi |
collection | PubMed |
description | The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based next-generation sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLA-matched subgroup. The worse outcome was mainly driven by a significantly higher non-relapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future. |
format | Online Article Text |
id | pubmed-8712639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87126392021-12-29 HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation Tsamadou, Chrysanthi Engelhardt, Daphne Platzbecker, Uwe Sala, Elisa Valerius, Thomas Wagner-Drouet, Eva Wulf, Gerald Kröger, Nicolaus Murawski, Niels Einsele, Hermann Schaefer-Eckart, Kerstin Freitag, Sebastian Casper, Jochen Kaufmann, Martin Dürholt, Mareike Hertenstein, Bernd Klein, Stefan Ringhoffer, Mark Frank, Sandra Neuchel, Christine Schrezenmeier, Hubert Mytilineos, Joannis Fuerst, Daniel Front Immunol Immunology The HLA-DRB3/4/5 loci are closely linked to the HLA-DRB1 gene. Mismatches in these loci occur with a frequency of about 8%–12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates. The aim of this study was to analyze a large cohort of German patients and their donors for HLA-DRB3/4/5 compatibility and to correlate the HLA-DRB3/4/5 matching status with the outcome of unrelated hematopoietic stem cell transplantation (uHSCT). To this end, 3,410 patients and their respective donors were HLA-DRB3/4/5 and HLA-DPB1 typed by amplicon-based next-generation sequencing (NGS). All patients included received their first allogeneic transplant for malignant hematologic diseases between 2000 and 2014. Mismatches in the antigen recognition domain (ARD) of HLA-DRB3/4/5 genes were correlated with clinical outcome. HLA-DRB3/4/5 incompatibility was seen in 12.5% (n = 296) and 17.8% (n = 185) of the 10/10 and 9/10 HLA-matched cases, respectively. HLA-DRB3/4/5 mismatches in the ARD associated with a worse overall survival (OS), as shown in univariate (5-year OS: 46.1% vs. 39.8%, log-rank p = 0.038) and multivariate analyses [hazard ratio (HR) 1.25, 95% CI 1.02–1.54, p = 0.034] in the otherwise 10/10 HLA-matched subgroup. The worse outcome was mainly driven by a significantly higher non-relapse mortality (HR 1.35, 95% CI 1.05–1.73, p = 0.017). In the 9/10 HLA-matched cases, the effect was not statistically significant. Our study results suggest that mismatches within the ARD of HLA-DRB3/4/5 genes significantly impact the outcome of otherwise fully matched uHSCT and support their consideration upon donor selection in the future. Frontiers Media S.A. 2021-12-14 /pmc/articles/PMC8712639/ /pubmed/34970261 http://dx.doi.org/10.3389/fimmu.2021.771449 Text en Copyright © 2021 Tsamadou, Engelhardt, Platzbecker, Sala, Valerius, Wagner-Drouet, Wulf, Kröger, Murawski, Einsele, Schaefer-Eckart, Freitag, Casper, Kaufmann, Dürholt, Hertenstein, Klein, Ringhoffer, Frank, Neuchel, Schrezenmeier, Mytilineos and Fuerst https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Tsamadou, Chrysanthi Engelhardt, Daphne Platzbecker, Uwe Sala, Elisa Valerius, Thomas Wagner-Drouet, Eva Wulf, Gerald Kröger, Nicolaus Murawski, Niels Einsele, Hermann Schaefer-Eckart, Kerstin Freitag, Sebastian Casper, Jochen Kaufmann, Martin Dürholt, Mareike Hertenstein, Bernd Klein, Stefan Ringhoffer, Mark Frank, Sandra Neuchel, Christine Schrezenmeier, Hubert Mytilineos, Joannis Fuerst, Daniel HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title |
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title_full |
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title_fullStr |
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title_full_unstemmed |
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title_short |
HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation |
title_sort | hla-drb3/4/5 matching improves outcome of unrelated hematopoietic stem cell transplantation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8712639/ https://www.ncbi.nlm.nih.gov/pubmed/34970261 http://dx.doi.org/10.3389/fimmu.2021.771449 |
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