Nonmyeloablative Allogeneic Stem Cell Transplant Strategies and the Role of Mixed Chimerism

Abstract

Experimental and clinical experiences have demonstrated successsful donor engraftment following nonmyeloablative preparative regimens. These less toxic conditioning strategies may be better tolerated with diminished transplant-related morbidity and mortality. Importantly, the intentional induction of mixed chimerism can be established following nonmyeloablative conditioning. This approach has the potential advantages of inhibiting graft-versus-host disease, presumably secondary to the persistence of host immunoregulatory cells, and providing a platform for the delivery of adoptive cellular immunotherapy with donor leukocyte infusions for patients with an underlying malignancy. This review will describe the preclinical evolution of nonmyeloablative transplant strategies, the rationale for considering these approaches, and the preliminary clinical experience with this novel allogeneic stem cell therapy.