Intensive therapy in multiple myeloma

Multiple myeloma is still an iocurable disease. With combioation chemotherapy the median survival is about 3 years. High-dose therapy with autologous or allogeneic stem cell support has been used in an attempt to improve response rate and survival. Promising results of this approach have led to even further dose iotensification with double highdose therapy end stem eel! support. Randomized studies are needed to address the issue of who might benefit from different treatment modalities. On this basis we conducted a prospective, randomized, multicenter phase III study of high-dose therapy io previously untreated multiple myeloma. In chapter 2 the feasibility of viocristine, adriarnycin and dexamethasone (V AD) administered as rapid iofusion is described as a fast ioduction regimen io multiple myeloma. In chapter 3 a potential explanation for failure of response to dexamethasone is described. The role of a glucocorticoid receptor splice variant in resistance to dexamethasone containing regimen will be discussed. In chapter 4 the results are presented of a prospective randomized multicenter study compariog iotensified chemotherapy treatment with iotensified chemotherapy followed by myelo-ablative therapy io untreated multiple myeloma. In chapter 5 the outcome of high-dose therapy with allogeneic stem cell transplantation as compared to iotensive treatment alone is described. In chapter 6 describes the feasibility of high-dose melphalan divided io 2 cycles to avoid the necessity ofreiofusion of tumor contaminated stem cel!s. In chapter 7 the prognostic relevance of cytogenetic analysis io multiple myeloma is discussed. In chapter 8 the iofluence of high-dose therapy on quality oflife is evaluated. In chapter 9 the cost aspects of high-dose therapy are described. In chapter 10 the results and relevance of the presented data will be discussed

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