The role of hematopoietic stem cell transplantation in the treatment of multiple myeloma.

The treatment of multiple myeloma has dramatically improved in the past 10 years. The availability of new drugs has broadened chemotherapy options; however, complete remissions (CR) are infrequent, and cure is still rare. High-dose therapy followed by autologous or allogeneic stem cell transplant has emerged as a promising means to increase remission rates and improve survival. Autologous transplants have not always shown survival benefits in randomized studies because the majority of patients who undergo transplant relapse, and patients given conventional therapy can receive salvage transplants at the time of relapse. CR has been found to reliably predict survival and thus the efforts to improve remission rates using autologous transplant include tandem transplants, targeted radiation, cytoprotective agents, or posttransplant immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, because of an immunologic graft-versus-myeloma effect. High transplant-related mortality associated with allogeneic stem cell transplantation is currentlythe major limitation to wider use of this modality. Although patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3- to 5-year survivals, only allograft recipients appear to enjoy long-term disease-free survival. Promising approaches designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies such as bone-seeking radioisotopes.