Synergistic Effect of KIR Ligands Missing and Cytomegalovirus Reactivation in Improving Outcomes of Haematopoietic Stem Cell Transplantation from HLA-matched Sibling Donor for Treatment of Myeloid Malignancies

The goal of this study was to evaluate the influence of KIR-HLA genotypes on the outcome of patients undergoing treatment for haematological malignancies by non-T-depleted lymphocyte haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donors. The prospective study was conducted at the Center of Hematology, University of Campinas, and 50 patients and their donors were followed up from 2008 to 2014. KIR and HLA class I genes were genotyped and patients grouped based on the presence of KIR ligands combined with KIR genotype of their respective donors. Patients with all KIR ligands present (n=13) had a significantly higher (p=0.04) incidence of acute graft-versus-host-disease (GVHD) than patients with one or more KIR ligands missing (n=37). The overall survival following transplantation of patients with myeloid malignancies (n=27) was significantly higher (p=0.035) in the group with one or more KIR ligands missing (n=18) than in the group with all ligands present (n=9). Presence of KIR2DS2 was associated with a worsening of HSCT outcome while reactivation of cytomegalovirus (CMV) infection improved the outcome of patients with one or more KIR ligands missing. Our results indicate that KIR-HLA interactions affect the outcome of the HLA-matched transplantation, particularly in patients with myeloid malignancies.