Hematopoeitic stem cell transplantation (HSCr) using a hap-loidentical family donor (HAPLO) was long thought to be non-fea-sible,essentially because of HLA incompatibility leading to graft rejection,severe acute (aGVH) and chronic (cGVH) graft versus host disease (GVH),severe infections and unacceptable non-relapse mortality (NRM).rnThe group in Perugia in the last decade of the past century[1],was the first to be successful by initiating a positive selection of CD34+ cells from peripheral blood stem cell (PBSC) collections,pro-viding T cell depleted grafts with very high doses of CD34+ cells to be infused.When combined with intensive conditioning regimen and profound immunosuppression,the Perugia group obtained the first demonstration of feasibility and efficacy.They later improved their results in acute myeloid leukemia (AML) by show-ing that a mismatch for natural killer (NK) cells in the killer-cell immunoglobulin-like receptor (KIR)-human leukocyte-antigen class Ⅰ (HLA1) donor to recipient direction[2]decreased consider-ably the relapse incidence (RI).Unfortunately this approach was associated with severe infections,a high NRM and in addition was cumbersome and difficult to reproduce in other non-expert centers.