High-dose chemotherapy in multiple myeloma

The median survival of conventionally treated patients with multiple myeloma is 3 years. Modifications of conventional chemotherapy have failed to show an improved survival rate in most randomized trials. Therapy regimens with dose-escalated alkylating agents (ie melphalan) have induced higher remission rates in comparison to conventional treatment modalities. With the support of autologous or allogeneic hematopoietic progenitor cells, it has been possible to reduce the hematoxicity of these dose-escalated treatments. The transplantation of autologous peripheral blood progenitor cells results in faster hematopoietic reconstitution with decreased high-dose therapy-related morbidity compared to autologous bone marrow. The randomized French myeloma trial and the pair-mate analysis of the results of the 'total therapy' including double autografting of the Barlogie group with data from the South Western Oncology Group (SWOG) showed a significant survival advantage for patients following autologous transplantation. Although a graft-versus-myeloma effect was described, the benefit of high-dose treatment with allogeneic transplantation is less clear, mainly due to the high transplantation-related mortality rate. In this paper, results of transplantation trials are summarized. Prognostic factors and future treatment modalities for myeloma are discussed.