Reduced-intensity allogeneic stem cell transplantation

The aim of reduced-intensity allogeneic stem cell transplantation is to exploit the graft-versus-tumor effect and reduce the toxicity associated with traditional ablative preparative regimens. Reduced-intensity regimens often use a purine analog with chemotherapeutic agents or low-dose total body irradiation. Postgrafting immunosuppression is variable and often consists of cyclosporine or tacrolimus plus methotrexate or mycophenolate mofetil. Regimen-related toxicity may be reduced using this approach, with a reduction in early mortality. Acute and chronic graft-versus-host disease continue to be problematic and are the primary causes of treatment-related mortality. The degree of myelosuppression is dependent on the regimen and the postgrafting immunosuppression. Myelosuppression is modest after 200 cGy of total body irradiation (with or without fludarabine), but it is more significant after regimens that use a purine analog with robust doses of chemotherapy. Stable mixed or full donor chimerism occurs with most regimens and graft rejection is more common in recipients of unrelated grafts. Reduced-intensity regimens are active in most hematologic malignancies and in some solid tumors, although the data in solid tumors are limited. Data suggest that rapidly growing malignancies require a more intensive regimen than indolent malignancies or those in remission. Reduced-intensity approaches have an appeal for nonmalignant diseases treated by allotransplantation. No prospective randomized trials have compared reduced-intensity approaches with conventional allotransplant preparation or postgrafting immunosuppression after reduced-intensity allografting. However, the strategy holds great promise and offers the possibility of curative therapy for patients who are ineligible for an ablative transplant.