Role Of Kir Genotype In Acute Myeloid Leukemia Treated With Stem Cell Transplant

Context: Natural killer (NK) cells play a major role in tumor surveillance, defense against viruses, and graft-versus-tumor effects after stem cell transplant (SCT). In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), the donor KIR genotype is not routinely considered when choosing a donor. Objective: To evaluate the relevance of the KIR genotype in a series of patients with AML/MDS submitted to SCT. Design: Retrospective cohort. Setting: Single-center study in a private referral hospital. Patients or Other Participants: Donors of any age and adult patients with a diagnosis of AML or MDS; 17 patients underwent haploidentical-SCT, and 18 patients underwent unrelated histoidentical-SCT, from 2015 to 2020. KIR genotype was assessed in donors. Main Outcome Measures: The association of KIR genotype and OS, RFS, EFS, and GVHD (III/IV and/or chronic). We consider patient ligands, donor KIR haplotype, B content, KIR inhibitor mismatches, presence of KIR2DS1 or KIR3DS1, activating KIRs matches, mismatching in KIR ligands, and the KIR-score. Secondary outcomes included KIR haplotype and GVHD and the association of KIR2DS2, KIR2DS4, and KIR2DL2 mismatch and KIR3DL2 with cytomegalovirus (CMV) reactivation. Results: Thirty-five patients and donors were included; median follow-up was 388 days. Median patient age was 51 years (range 19–71); median donor age was 32 years (range 13–48). Diagnoses were AML (n=30) and SMD (n=5). One-year OS was 64% in haploidentical-SCT and 80% in unrelated histoidentical-SCT. KIR genotype was Bx in 75% of donors. KIR2DL1-mismatch was associated with non-significant improvements in 2-year OS (84% vs 55%, p=0.18) and PFS (84% vs 60%, p=0.21). Regarding mismatches in KIR ligands, the presence of mismatches in the GVH direction was associated with an increased risk of GVHD (50% vs 14%; P=0.08). The absence of the KIR2DS2 gene resulted in a higher risk of CMV reactivation, 80% (12/15) vs 45% (9/20) in the KIR2DS2-positive group (p=0.005). Patients with CMV reactivation had a trend toward higher incidence of GVHD (28% vs 7%, p=0.20). Conclusions: KIR genotyping can provide useful information to select donors in AML/MDS. Larger cohort studies are needed to confirm these findings.