Individual HLA alleles and risk of graft-versus-host disease after haematopoietic stem cell transplantation from HLA-ide

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ORIGINAL ARTICLE

Individual HLA alleles and risk of graft-versus-host disease after haematopoietic stem cell transplantation from HLA-identical siblings Ivana Shawkatová 1 Monika Homolová 1

&

Eva Bojtárová 2 & Monika Kováčová 2 & Kristína Klučková 1 & Mária Kušíková 2 & Martin Mistrík 2 &

Received: 7 February 2020 / Accepted: 30 April 2020 # Institute of Molecular Biology, Slovak Academy of Sciences 2020

Abstract Graft-versus-host disease (GVHD) in its acute (aGVHD) and chronic (cGVHD) form remains one of the most serious complications of allogeneic haematopoietic stem cell transplantation (allo-HSCT). There are several risk factors known to be associated with GVHD development. Some reports suggest that certain human leukocyte antigen (HLA) variants may influence the incidence of GVHD. The aim of our study was to analyse possible association between individual HLA alleles and the occurrence of aGVHD and cGVHD in patients following allo-HSCT from HLA-identical sibling donors. We have retrospectively reviewed medical records of 96 patients who received a transplant in the years 1994–2008. Cumulative incidence of acute GVHD was 31.3% and that of chronic GVHD was 26.0%. Recipients carrying the HLA-A*01, -DRB1*03 and -DQB1*03 alleles showed a statistically significantly lower incidence of aGVHD. Furthermore, the HLA-DQB1*06 allele was associated with a higher incidence of cGVHD. Each of these alleles was confirmed by logistic regression analysis as an independent factor with impact on GVHD development. Our results support findings of authors showing an association between certain HLA variants and GVHD appearance. However, other authors assume that there is no convincing evidence for such an association. Therefore, when taking into account limitations of our study design and the significant inconsistency in the results of the previous reports, a careful approach in judgement is required. To conclude, in our view, the prognostic value of individual HLA variants for GVHD development in a setting of HLA-identical allo-HSCT does not seem to be of great clinical relevance. Keywords Haematopoietic stem cell transplantation . Human leukocyte antigens . Graft-versus-host disease

Abbreviations aGVHD Acute graft-versus-host disease allo-HSCT Allogeneic haematopoietic stem cell transplantation cGVHD Chronic graft-versus-host disease CI Confidence interval CsA Cyclosporin A HLA Human leukocyte antigens

* Ivana Shawkatová [email protected] 1

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia

2

Department of Hematology and Transfusiology, Faculty of Medicine, Comenius University in Bratislava, Slovak Medical University and University Hospital in Bratislava, Bratislava, Slovakia

HSCT miHA MTX

Haematopoietic stem cell transplantation Minor histocompatibility antigens Methotrexate

Introduction Allogeneic haematopoietic stem cell transplantation (alloHSCT) is currently a well-established treatment procedure for a variety of haematological and non-haematological l