Donor-versus-recipient natural killer (NK) cell alloreactivity derives from a mismatch between donor NK clones, carrying specific inhibitory receptors for self MHC class I molecules, and MHC class I ligands on recipient cells. When faced with mismatched allogeneic targets, these donor NK clones sense the missing expression of self HLA class I alleles and mediate alloreactions. Transplantation from NK alloreactive haploidentical donors controls acute myeloid leukemia relapse and improves engraftment without causing graft-versus-host disease.