Reinventing bone marrow transplantation. Nonmyeloablative preparative regimens and induction of graft-vs-malignancy effect.

The therapeutic benefit of allogeneic hematopoietic transplantation is due largely to an immune graft-vs-malignancy effect. Most of the evidence for such an effect has come from studies of allogeneic transplantation in leukemia. In patients with susceptible malignancies who relapse following an allogeneic transplant, infusion of donor lymphocytes can induce durable remissions. Use of less toxic, nonmyeloablative preparative regimens permits engraftment and generation of graft-vs-malignancy effects. This strategy permits allogeneic transplantation to be used in older patients and those with comorbidities who cannot tolerate conventional high-dose preparative regimens. The long-term efficacy of nonmyeloablative preparative regimens and induction of graft-vs-malignancy effects remains to be determined. Also, further clinical trials are required to address various unresolved issues and to compare this strategy with standard, myeloablative transplantation regimens.