HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation

Tsamadou C, Engelhardt D, Platzbecker U, Sala E, Valerius T, Wagner-Drouet E, Wulf G, Kroeger N, Murawski N, Einsele H, Schaefer-Eckart K, Freitag S, Casper J, Kaufmann M, Duerholt M, Hertenstein B, Klein S, Ringhoffer M, Frank S, Neuchel C, Schrezenmeier H, Mytilineos J, Fuerst D (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 12

Article Number: 771449

DOI: 10.3389/fimmu.2021.771449

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.

Involved external institutions

DRK-Blutspendedienst Baden-Württemberg - Hessen / German Red Cross Blood Donor Service Baden-Wuerttemberg – Hessen Germany (DE) Universität Ulm Germany (DE) Universität Leipzig Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) Germany (DE) Georg-August-Universität Göttingen Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Universitätsklinikum Würzburg Germany (DE) Klinikum Nürnberg Germany (DE) Universität Rostock Germany (DE) Klinikum Oldenburg Germany (DE) Robert-Bosch-Krankenhaus Germany (DE) Evangelische Kliniken Essen-Mitte Germany (DE) Klinikverbund Bremen (Gesundheit Nord) Germany (DE) Universitätsklinikum Mannheim Germany (DE) Städtisches Klinikum Karlsruhe Germany (DE) Deutsches Register für Stammzelltransplantationen e.V. (DRST) Germany (DE)

How to cite

APA:

Tsamadou, C., Engelhardt, D., Platzbecker, U., Sala, E., Valerius, T., Wagner-Drouet, E.,... Fuerst, D. (2021). HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.771449

MLA:

Tsamadou, Chrysanthi, et al. "HLA-DRB3/4/5 Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation." Frontiers in Immunology 12 (2021).

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