Reducing transplant toxicity

Conventional myeloablative allogeneic hematopoietic cell transplantation produces considerable morbidity and mortality. These generally limit this treatment to patients in good medical condition who are younger than 55 years of age. T-cell-mediated graft-versus-tumor effects play a key role in the elimination of malignancy after allografting. Several investigators have sought to reduce regimen-related toxicities while optimizing graft-versus-tumor effects. Strategies can be broadly classified as (1) reduced-intensity regimens that retain some toxicity, and (2) minimally myelosuppressive regimens that rely on immunosuppression for allogeneic engraftment and resultant graft-versus-tumor effects. Although follow-up has been short, preliminary results are encouraging. Current challenges include defining a regimen that will facilitate full donor engraftment while minimizing toxicities and graft-versus-host disease. If long-term efficacy is demonstrated, such strategies will expand the options for patients who would not qualify for conventional allogeneic transplants.