Nonmyeloablative therapy and allogeneic hematopoietic stem cell transplantation

The toxicities associated with conventional myeloablative therapy and allogeneic hematopoietic stem cell transplantation (SCT) limit the use of this potentially curative approach to relatively healthy young patients. The risk of treatment-related morbidity and mortality with conventional allogeneic SCT ranges from 10% to 50%, depending on the age of the patient, HLA histocompatibility, diagnosis and disease status, and presence or absence of comorbid conditions. The main goals of conventional high-dose preparative regimens are to eradicate the malignancy and induce adequate host immunosuppression to prevent graft rejection. However, accumulated data indicate that the currently used myeloablative regimens frequently do not eradicate the malignant clone, and that an immune-mediated effect between donor immunocompetent T lymphocytes and host tumor cells seems to induce a major therapeutic benefit, accounting for the significantly lower incidence of leukemic relapse seen with allogeneic SCT compared to autologous or syngeneic SCT. These observations have led to the development of newer treatment modalities focusing on the induction of host tolerance to donor cells followed by the administration of scheduled donor T-lymphocyte infusions. Preliminary clinical data are encouraging but need to be confirmed in well-designed prospective controlled trials with direct comparison to conventional allogeneic SCT and extended follow-up to determine the durability of responses and the consequences of late complications such as chronic graft-vs-host disease on the patient's quality of life.