Integrating killer cell immunoglobulin-like receptor highresolution genotyping for predicting transplant outcomes in allogeneic hematopoietic stem cell transplantation.

The success of hematopoietic stem cell transplantation (HSCT) partly relies on the beneficial graft-versus-leukemia effect, mediated by alloreactive natural killer cells through their killer cell immunoglobulin-like receptors (KIR). Conflicting results have been reported regarding the impact of the KIR immunogenetic system on HSCT outcomes with a scarcity of data interrogating the effect of KIR allelic polymorphism. With the aim of filling this gap, donor KIR genes derived from a national cohort of 1,247 HLA-matched transplanted donor/recipient pairs were determined at a high-resolution and tested in Cox proportional hazards models. Donor/recipient pairs bearing a KIR2DS4*00101-HLA-C1/C2/A11 interaction showed a significant detrimental impact on progression-free survival, overall survival, transplant-related mortality and chronic graft-versus-host disease in multivariable analysis. Strong KIR2DL2/L3-HLA-C1 and especially KIR2DL3*00501 and *015 interactions showed a significant increase in the incidence of chronic graft-versus-host disease compared to donor/recipient pairs with missing ligands. Strongly inhibiting KIR3DL1-HLA-B and HLA-A (Bw4) interactions were associated with a reduced relapse incidence as compared to weak and non-inhibiting interactions. Our study indicates that high-resolution KIR genotyping informs post-transplant outcomes with a seemingly higher protection of educated natural killer cells.