LAG-3 genotype in haematopoietic stem cell transplant from HLA identical sibling donor

Abstract

BACKGROUND: Allogeneic Haematopoietic Stem Cell Transplant is the treatment of choice in various malignant hemopathies. Graft-versus-host-disease is the main complication, but a lack of clarity exists considering genetic differences between donor and recipient, or the mechanisms that modulate the immune outcome. LAG-3 (CD223) is a surface protein belonging to an

immunoglobulin superfamily and its function is to inhibit the immune response of T- lymphocytes. Researchers does not discuss whether the LAG-3 genotype conditions are related

the post-allogeneic Haematopoietic Stem Cell Transplant complications. HYPOTESIS AND OBJECTIVE: The aim of this retrospective multicenter single cohort study is to analyse the association of allogeneic Haematopoietic Stem Cell Transplant with incidence of acute Graft-versus-host-disease based on the donor’s LAG-3 genotype in 16 hospitals from Spanish Group of Haematopoietic Transplant (GETH) between 2000 and 2014, coordinated by ICO Girona. METHODS: A registry of 797 patients with an allogenic Haematopoietic Stem Cell Transplant from an HLA-identical sibling donor was described and analysed all the data collected. Polymorphism rs870849 C>T of the LAG-3 gene was analyzed in donors. Clinical events of patients whose donor was homozygous for allele C were compared against homozygous for the allele T or heterozygous C/T. This was done to determine polymorphism with Allelic discrimination being performed.

RESULTS: No statistically significant differences were found for the incidence of acute Graft- versus-host-disease between homozygous genotypes for allele C with respect to homozygous

for allele C or heterozygous C/T. In contrast, statistically significant differences were found in Disease-free-survival (55.3% vs 41%, p-0.02). Overall Survival was also worse in patients whose donor had CT/TT (57% vs 43.9%, p-0.003). Additionally, there is a higher increase in relapses for CC (29.4% vs 38.5, p-0.074), and also in transplant-related mortality in the same group (20.2% vs 31.7%, p-0.002). CONCLUSIONS: The donor's LAG-3 genotype is associated with differences in OS after an allogeneic Haematopoietic Stem Cell Transplant from an HLA-identical sibling donor. Therefore, it is associated with an increase in relapse and TRM. However, there are no significant differences in the incidence of acute Graft-versus-host-disease