The first of these trials was conducted by the Intergroupe Français du Myélome (IFM) in which 200 untreated multiple myeloma patients under 65 years of age were randomized to receive either conventional chemotherapy or high dose chemotherapy in combination with ASCT. Since its initial description, there have been seven randomized clinical trials comparing high-dose ASCT to conventional chemotherapy ( Table 1). The observation that high-dose melphalan had significant anti-tumor activity and could overcome primary drug resistance was confirmed in a later study. High-dose chemotherapy was initially explored as a therapeutic approach in the 1980’s after a landmark study demonstrated its effectiveness in inducing 100-percent complete remission rates in nine high-risk multiple myeloma and plasma cell leukemia patients after preconditioning with high-dose melphalan. Treatment complications and later resistance were associated with poor outcomes with median overall survival ranged between two and three years. The standard of care for multiple myeloma patients prior to the incorporation of ASCT was conventional chemotherapy using melphalan and prednisone with the primary goals of treatment being achievement of partial response or disease stabilization. The advent of autologous stem cell transplantation has changed the therapeutic landscape for the management of multiple myeloma and has been the standard frontline therapy for younger patients with normal renal function since the 1990’s. The role of autologous stem cell transplantation in multiple myeloma
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