Non-myeloablative allogeneic stem cell transplant: Achievements and perspectives

In the past concept, conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) were assumed to have two roles: myeloablation and immunosuppression. Recent clinical and experimental data have shown that intense immunosuppression, rather than myeloablation, is the primary requirement for stable engraftment and that the main therapeutic component of allogeneic HSCT is attributed to graft-versus-leukemia/tumor (GVL/T) effect mediated by donor-derived T cells. Based on these findings, a new strategy of non-myeloablative stem cell transplantation (NST) has been developed for patients who are ineligible for conventional stem cell transplantation (CST) because of the old age or organ dysfunction. Recent reports from many transplant centers have shown that application of NST decreased regimen-related toxicities (RRT), while associated with consistent stable engraftment. In this review we overview the clinical development (background, clinical experience), remaining problems and future directions of NST.