The role of high-dose chemotherapy in the treatment of multiple myeloma: a controversy

Abstract

Background: Minimal criteria for the diagnosis of multiple myeloma are provided. Monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, primary systemic amyloidosis and metastatic carcinoma must be included in the differential diagnosis. Patients with multiple myeloma should not be treated unless they have an increasing M-protein in the serum or urine, development of anemia, hypercalcemia, renal insufficiency, lytic lesions, fractures or extra-medullary plasmacytomas.

Patients and methods: This is a review of patients treated with chemotherapy, autologous stem-cell transplantation and allogeneic transplantation.

Results: Comparisons of melphalan and prednisone with a variety of combinations of therapeutic agents produces a higher response rate than with melphalan and prednisone but no significant difference in overall survival. Autologous stem-cell transplantation produces a higher response rate and some prolongation of survival but is not curative. Allogeneic transplantation is associated with a mortality of 40% and is not curative.

Conclusions: If the patient is younger than 70 years, the physician should consider the possibility of an autologous peripheral blood stem-cell transplant. Ideally, this should be done as part of a prospective study. Hematopoietic stem cells are damaged by alkylating agents so they must be collected before these agents are given. Autologous stem-cell transplantation does not produce a cure and most patients will relapse. The appropriate timing of an autologous stem-cell transplant has not been ascertained. Hopefully, better preparative regimens and the removal of contaminated tumor cells from the peripheral blood will make an autologous transplant more effective. Another major question is whether double (tandem) transplants are superior to a single autologous stem-cell transplant. A current French Myeloma Group Study randomized study should answer this question. Allogeneic transplantation for multiple myeloma must be made safer because the transplant-related mortality is 40%. The relapse of multiple myeloma following allogeneic transplant is a major problem and consequently the preparative regimens must be improved. The infusion of donor lymphocytes following relapse after an allogeneic transplant is useful. New approaches with immunologic aspects including the use of dendritic cells and vaccines are of potential importance for the future.