Genetic predisposition of acute graft-versus-host disease after hematopoietic stem cell transplantation from an HLA-identical sibling donor: a retrospective and multicenter cohort study

Abstract

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a very used treatment for several hematological disorders, especially for acute leukemia. But this type of HSCT is associated with a high incidence of morbidity and mortality. The main complication of HSCT is the graft-versus-host disease (GVHD), an immunological disorder that affects many organs systems. The frequency of GVHD is directly related to the degree of mismatch between patient-donor HLA proteins. The ideal donor has to be HLA-identical with the patient to avoid GVHD. But 40% of recipients of HLA-identical grafts develop systemic GVHD. Thus, there are other disparities that can be associated with GVHD, such as hidden HLA disparities or minor histocompatibility antigens mismatches. Objectives To determine the incidence of acute GVHD and overall survival (OS) and disease-free survival (DFS) after allogeneic HSCT from an HLA-identical sibling donor with: - HLA-DPB1 mismatch - mHag HA-1 mismatch - Male-specific HY-antigens mismatch Methods A longitudinal retrospective and multicenter cohort composed by 1377 patients receiving an allogeneic HSCT from an HLA-identical sibling donor between 1992 and 2014. All the data are already collected in the Biobank of IDIBGI. Results Our preliminary results showed that mHag HA-1 and HY-antigens disparities are significant risk factors of grades II-IV acute GVHD after HLA-identical sibling donor HSCT. Nevertheless, only HY-antigens mismatch influences OS and DFS at 10 years. We did not find association between HLA-DPB1 mismatch and grades II-IV acute GVHD