Abstract The Bone Marrow Transplant (BMT)/Leukemia Program at Washington University ranks among the largest in the United States, performing over 400 transplants annually, including over 200 allogeneic transplants. The program has been affiliated with the BMT Clinical Trials Network (CTN) since its inception, initially as part of the Case Western Consortium, and more recently as a Core Center since 2011. During this time, our institution has made significant contributions to CTN through clinical trials accrual and trial design input. As part of this application for renewal as a Core Clinical Center, we propose a phase II clinical trial incorporating the use of a novel cellular therapy into a haploidentical transplant platform for elderly patients with relapsed refractory AML. The basis for this proposal is the demonstration that NK cells stimulated ex vivo with a cocktail of cytokines (IL12, IL15, IL18), exhibit an enhanced memory–like response to subsequent AML cell exposure both in vitro and in vivo in a mouse xenograft model. These observations led to a phase I dose- finding clinical trial to establish safety of haploidentical cytokine-induced memory-like (CIML) NK cells as therapy for elderly adults with relapsed AML, which has been concluded, and an ongoing phase II trial to define efficacy, with favorable preliminary results. On this basis, we propose to incorporate this CIML NK cell approach into a backbone of haploidentical donor stem cell transplantation with reduced intensity conditioning and post-transplant cyclophosphamide for elderly adults with relapsed AML. Our hypothesis is that this strategy will lower the incidence of relapse in this high risk population while preserving the tolerability of the reduced intensity conditioning approach. Completion of this study would require accrual of 30 patients, anticipated over a 2-year period in the context of a multi-center trial.