Autologous bone marrow transplantation for multiple myeloma

Intensive cytotoxic chemotherapy has proven feasible and capable of inducing more marked tumor cytoreduction including true complete remissions in a disease for which such an approach was almost unthinkable 10 years ago because of patients' advanced age and often debilitated clinical condition. Important for the development of such intensive therapy was the recognition that high doses of dexamethasone and VAD were capable of inducing substantial cytoreduction and bone marrow remission without compromising normal hemopoietic stem cell reserve. Autologous hemopoietic stem cells should be collected early in the disease course before major damage from alkylating agents has been inflicted. Utilization of hemopoietic growth factors, especially GM-CSF, both for the procurement of blood stem cells and after autotransplantation, to further accelerate hematologic reconstitution has reduced the risks of infection and severe extramedullary toxicities. When considering the indications for autotransplantation in multiple myeloma, an individual patient's prognosis with standard therapy has to be weighed against the potential gain from and risk associated with autologous transplantation. Relatively little benefit can be expected when several adverse features coincide, especially high-tumor burden, resistance to standard doses of therapy, and prolonged exposure to alkylating agents. In such a setting, it will be difficult to obtain hemopoietic stem cells of adequate quantity and quality, and the likelihood of major cytoreduction resulting in prolonged disease control of more than 1 year is low. Hemopoietic stem cells collected after limited prior drug exposure will ensure prompt and complete hematologic reconstitution. Remissions exceeding 24 months can be anticipated when tumor burden is low and/or myeloma is still sensitive to standard doses of therapy. Greatest benefit can be anticipated from transplantation early in remission. Based on more extensive experience in leukemia and lymphoma, primary responsive disease provides the only clinical setting in which the curative potential of autotransplant-supported intensive therapy can be assessed. To overcome patient selection bias, clinical trials comparing prospectively high-dose therapy with standard doses of treatment are warranted.