Stem cell transplantation-harnessing of graft-versus-malignancy

Allogeneic transplantation can cure a number of hematologic malignancies; however, the cost in morbidity and mortality is high. Much of the toxicity is a direct consequence of the intensity of the conditioning regimen. It has gradually been recognized that the conditioning regimen is important but not critical for the success of transplantation, particularly in the less aggressive hematologic malignancies. The graft-versus-malignancy effect, that is, the recognition of residual cancer cells by the T cells of the donor, is a critical component of the transplantation process.

This effect has been emphasized over high-dose therapy by using less intensive, and therefore less toxic conditioning regimens, thus allowing the graft-versus-malignancy effect to predominate. Reduced-intensity conditioning regimens have allowed the application of transplantation to older patients and to patients with underlying medical problems that preclude full-dose transplantation.

Although the long-term results of this type of approach have not yet been defined, it appears to be effective in diseases such as chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphomas that are not intrinsically very aggressive. Although the therapy appears to be valuable, concerns about delayed immune reconstitution and graft-versus-host disease remain.