T-cell-depleted hematopoietic stem cell (HSC) transplantation from an HLA-haploidentical relative (Haplo HSCT) may represent a suitable and effective transplant option, as it is capable of rescuing not only adult patients with high-risk acute myeloid leukemias (AML) but also children with relapsed acute lymphoblastic leukemia (ALL), as shown by the two representative cases presented in this study. In Haplo HSCT, the anti-leukemia effect is mediated by "alloreactive" (i.e. KIR/HLA-mismatched) NK cells originated from donor HSCs. The availability of suitable KIR-specific monoclonal antibodies allows the prompt identification of alloreactive NK cell subsets as well as their quantification. This is important for selection of the most suitable donor and evaluation of the generation and persistence of these alloreactive NK cells after transplantation. In view of the favorable clinical outcome of children with chemo-resistant ALL, Haplo HSCT from an NK-alloreactive relative could become a first option in these high-risk leukemia patients.