BACKGROUND: The effect of natural killer (NK) cell alloreactivity on outcome of unrelated stem cell transplantation (SCT) remains controversial. Killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen C and B epitopes on target cells, thereby regulating NK cell activity. The KIR genes are polymorphic and two broad haplotypes exist: KIR-haplotype A mainly encode for inhibitory receptors and only for one activating (KIR2DS4), whereas the group B haplotype encodes more for activating KIRs (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DS5 und KIR3DS1). METHODS: The impact of KIR ligand mismatch on the number of activating and inhibitory donor KIR genes and on KIR-haplotype was studied on outcome of 142 patients with leukemia, who received standard myeloablative conditioning followed by in vivo T-cell depleted (ATG) unrelated SCT. RESULTS: In a multivariate analysis KIR ligand mismatch had significantly higher treatment related mortality (RR 2.206, P = 0.03), resulting in reduced overall (RR 2.015, P = 0.02) and disease-free survival (RR 1.924, P = 0.03). In contrast, SCT from donors with group A haplotype (P = 0.003) or with low number of activating KIR genes (P = 0.005) resulted in reduced relapse rate with improved disease-fee survival (P = 0.04). This effect was seen only in acute myeloid leukemia/myelodysplastic syndrome and to a less extent in chronic myeloid leukemia. No effect was seen for acute lymphoblastic leukemia. CONCLUSIONS: After in vivo T-cell depleted (ATG) unrelated stem cell transplantation with donors carrying low number of activating KIR genes (group A KIR haplotype), the risk of relapse is reduced and resulted in a significantly better disease-free survival.
