Bone marrow transplantation in multiple myeloma

Modifications of standard therapy with melphalan and prednisone have not improved the prognosis of patients with multiple myeloma. Encouraging results with high doses of intravenously administered melphalan have generated interest in marrow-ablative therapy with hemopoietic stem cell support. Experience in about 400 patients receiving alkylating agents, sometimes with added total body irradiation, demonstrates partial remissions in virtually all patients with advanced and refractory myeloma, but complete remissions (CR) in less than one-half, even when transplants were performed for responsive disease with low tumor burden. Despite patient and disease heterogeneity, different sources of hemopoietic stem cells (allogeneic or autologous, bone marrow or blood), ex vivo purging of autografts, and different preparative regimens, some general recommendations can be made: (1) Allogeneic BMT should be reserved for patients under age 50, where transplant-related mortality can be expected not to exceed 30%; 40% will achieve CR with a 3-year relapse-free survival expectation of 70%, and (2) With autologous transplantation, low mortality under 10% and marked therapeutic benefit (> 30% CR, 80% overal survival at > 3 years) seem to be achievable mainly if performed when tumor bulk is low and standard doses of therapy are still effective. Because of the encouraging results even in patients older than 60 years, hemopoietic stem cell grafting should be seriously considered as part of an overall treatment strategy, in order to avoid irreversible normal hemopoietic stem cell damage from nitrosoureas and radiation to marrow-containing bones.