Nonmyeloablative stem cell transplants

Allogeneic stem cell transplantation (SCT) is a curative procedure in a number of hematologic malignancies, but its efficacy is limited by its toxicity, much of which is consequent upon the myeloablative conditioning regimens currently used. The recent demonstration that an immunologically mediated graft-versus-leukemia effect plays a central role in delivering the anti-leukemic effect of an allograft has led to a fundamental reevaluation of the role of conditioning therapy in allogeneic transplantation. Recent animal studies have demonstrated that stem cell engraftment can occur using conditioning regimens that are minimally myelotoxic. This has prompted the development of less toxic nonmyeloablative conditioning protocols, the goal of which is to achieve donor stem cell engraftment allowing the graft-versus-tumor effect of the allograft to be exploited as the primary anti-leukemic strategy. Preliminary results using such nonmyeloablative clinical protocols confirm that durable engraftment of allogeneic stem cells can be achieved with a marked reduction in the immediate toxicity of transplantation. The extent to which this radically different transplant strategy allows the delivery of a sustained anti-leukemic effect is unclear at present, but it is likely that this approach will make an important contribution to allogeneic SCT in the future.