CT-163: Role of KIR Genotype in Haploidentical Stem Cell Transplant

Abstract

Context Natural killer cells (NK) play a major role in defense against viruses and graft-versus-tumor effect. NK functions are regulated by killer-cell-immunoglobulin-like-receptor (KIRs) and their ligands (HLA class I molecules). In haploidentical stem cell transplantation (Haplo-SCT), donor KIR genotype is not routinely considered when choosing an “ideal donor”. Objective Evaluate the relevance of KIR genotype in a series of patients with hematologic malignancies submitted to Haplo-SCT. Design Retrospective cohort study. Setting Single-center study in a private referral hospital. Patients or other participants Donors and patients over 18 years old submitted to Haplo-SCT with post-transplantation cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis, from 2015-2020. KIR genotype was studied in donors. Patients whose donors' blood samples were insufficient to determine KIR genotype were excluded. Main outcome measures We analyzed the impact of the KIR genotype on overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), and GVHD. The variables include: patient ligands (C1×/C2, Bw4, and HLA 3-11), donor KIR haplotype, B content, KIR inhibitor mismatches, presence of KIR2DS1 or KIR3DS1, activating KIRs matches, mismatching in KIR ligands, and the iKIR score. Secondary outcomes included the impact of KIR2DS2, KIR2DS4, KIR2DL2 mismatch, and KIR3DL2 on cytomegalovirus (CMV) reactivation. Results Thirty patients and donors were included, with a median follow-up of 532 days. Median age of patients and donors were 45 years and 37 years, respectively. The main diagnosis was acute myeloid leukemia (40%). The cohort's 2-year OS was 63%. Patients with C1/x ligands (70%, n=21) presented a higher 1-year EFS than patients with C2/2 (75% vs 23% p=0.015). KIR2DL2 mismatch showed an improvement in 1-year OS (84% vs 20%, p Conclusions KIR genotyping can provide useful information to select the donor for Haplo-SCT. Larger cohort studies are needed to confirm these findings.