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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, Vol. 12, 771449, 2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tsamadou, C, Engelhardt, D, Platzbecker, U, Sala, E, Valerius, T, Wagner-Drouet, E, Wulf, G, Kröger, N, Murawski, N, Einsele, H, Schaefer-Eckart, K, Freitag, S, Casper, J, Kaufmann, M, Dürholt, M, Hertenstein, B, Klein, S, Ringhoffer, M, Frank, S, Neuchel, C, Schrezenmeier, H, Mytilineos, J & Fuerst, D 2021, 'HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation', FRONT IMMUNOL, vol. 12, 771449. https://doi.org/10.3389/fimmu.2021.771449

APA

Tsamadou, C., Engelhardt, D., Platzbecker, U., Sala, E., Valerius, T., Wagner-Drouet, E., Wulf, G., Kröger, N., Murawski, N., Einsele, H., Schaefer-Eckart, K., Freitag, S., Casper, J., Kaufmann, M., Dürholt, M., Hertenstein, B., Klein, S., Ringhoffer, M., Frank, S., ... Fuerst, D. (2021). HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation. FRONT IMMUNOL, 12, [771449]. https://doi.org/10.3389/fimmu.2021.771449

Vancouver

Tsamadou C, Engelhardt D, Platzbecker U, Sala E, Valerius T, Wagner-Drouet E et al. HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation. FRONT IMMUNOL. 2021;12. 771449. https://doi.org/10.3389/fimmu.2021.771449

Bibtex

@article{a5ee98e139964a1288b6244516d429e5,
title = "HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation",
abstract = "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.",
author = "Chrysanthi Tsamadou and Daphne Engelhardt and Uwe Platzbecker and Elisa Sala and Thomas Valerius and Eva Wagner-Drouet and Gerald Wulf and Nicolaus Kr{\"o}ger and Niels Murawski and Hermann Einsele and Kerstin Schaefer-Eckart and Sebastian Freitag and Jochen Casper and Martin Kaufmann and Mareike D{\"u}rholt and Bernd Hertenstein and Stefan Klein and Mark Ringhoffer and Sandra Frank and Christine Neuchel and Hubert Schrezenmeier and Joannis Mytilineos and Daniel Fuerst",
note = "Copyright {\textcopyright} 2021 Tsamadou, Engelhardt, Platzbecker, Sala, Valerius, Wagner-Drouet, Wulf, Kr{\"o}ger, Murawski, Einsele, Schaefer-Eckart, Freitag, Casper, Kaufmann, D{\"u}rholt, Hertenstein, Klein, Ringhoffer, Frank, Neuchel, Schrezenmeier, Mytilineos and Fuerst.",
year = "2021",
doi = "10.3389/fimmu.2021.771449",
language = "English",
volume = "12",
journal = "FRONT IMMUNOL",
issn = "1664-3224",
publisher = "Lausanne : Frontiers Research Foundation",

}

RIS

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 -