High-dose melphalan with autologous hematopoietic SCT (HSCT) improves response rates and survival in myeloma. This is despite the fact that unlike other hematologic malignancies treated with high-dose therapy and autotransplantation, autografted myeloma patients continue to relapse several years after transplantation and the procedure is not curative in the majority of patients. However, patients surviving for several years with essentially normal quality of life may be considered to be 'operationally cured.' Also, unlike with other hematologic malignancies relapsing after an autograft, recurrent disease can be treated with novel agents or repeat high-dose chemotherapy and autologous or allogeneic HSCT-and long-term survival is seen in a number of patients after relapse. Although tandem transplantation is clearly superior to a single autograft, it is unclear if this should be offered to all patients routinely or only to those not attaining CR after one transplant. It is also unclear if novel agents should be used before transplantation or reserved for relapse. Despite their excellent activity, there is no evidence that novel agents such as thalidomide, bortezomib and lenalidomide can replace high-dose chemotherapy and HSCT, and the best strategy is to use all options in all eligible patients at appropriate stages of the disease.
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