HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
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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.
in: FRONT IMMUNOL, Jahrgang 12, 771449, 2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation
AU - Tsamadou, Chrysanthi
AU - Engelhardt, Daphne
AU - Platzbecker, Uwe
AU - Sala, Elisa
AU - Valerius, Thomas
AU - Wagner-Drouet, Eva
AU - Wulf, Gerald
AU - Kröger, Nicolaus
AU - Murawski, Niels
AU - Einsele, Hermann
AU - Schaefer-Eckart, Kerstin
AU - Freitag, Sebastian
AU - Casper, Jochen
AU - Kaufmann, Martin
AU - Dürholt, Mareike
AU - Hertenstein, Bernd
AU - Klein, Stefan
AU - Ringhoffer, Mark
AU - Frank, Sandra
AU - Neuchel, Christine
AU - Schrezenmeier, Hubert
AU - Mytilineos, Joannis
AU - Fuerst, Daniel
N1 - 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.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2021.771449
DO - 10.3389/fimmu.2021.771449
M3 - SCORING: Journal article
C2 - 34970261
VL - 12
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 771449
ER -