Reduced human leukocyte antigen mismatching is associated with more favourable outcomes after unrelated donor haematopoietic stem cell transplantation

Author:

Valatkaite‐Rakstiene Beatrice12ORCID,Cekauskiene Rita12,Zvirblis Tadas3,Jakubauskas Arturas12ORCID

Affiliation:

1. State Research Institute Centre for Innovative Medicine Vilnius Lithuania

2. Hematology, Oncology and Transfusion Medicine Centre Vilnius University Hospital Santaros Klinikos Vilnius Lithuania

3. Department of Human and Medical Genetics Institute of Biomedical sciences Faculty of Medicine Vilnius University Vilnius Lithuania

Abstract

AbstractThe patient–donor human leukocyte antigen (HLA) match remains the most important prognostic factor for successful unrelated donor haematopoietic stem cell transplantation (UD‐HSCT). This single‐centre study comprised 125 adult patients with malignant haematological diseases undergoing their first UD‐HSCT. The primary goal of this study was to validate the impact of HLA matching on HSCT outcomes, specifically at the HLA‐DPB1 and HLA‐DRB3/4/5 loci. A multivariable Cox regression analysis with a backward selection algorithm was employed to assess the associations of selected prognostic factors with outcomes after UD‐HSCT. Any HLA locus mismatch was found to be associated with an increased incidence of grade II–IV acute graft versus host disease (aGvHD) at 100 days (p = .031; hazard ratio [HR] 1.935) and 6 months (p = .004; HR 2.284) after HSCT. The results of the following analyses also confirmed the strong impact of HLA‐DPB1‐only mismatch on the incidence of grade II–IV aGvHD at 100‐day (p = .006; HR 2.642) as well as at 6‐month (p = .007; HR 2.401) time periods. The HLA‐DPB1‐only mismatch was also shown to be statistically significantly associated with lower relapse incidence (p = .034; HR 0.333). The impact of the HLA‐DRB3/4/5 mismatch on outcomes was inconclusive, though the two and more HLA‐DPB1 + DRB3/4/5‐only mismatches showed a trend towards worse outcomes than a single mismatch. Based on our findings and those of more comprehensive studies, the extended HLA loci typing of patients and donors is suggested to avoid unexpected HLA mismatches during the UD selection.

Publisher

Wiley

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine,Immunology

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