In this article, Pandit and Vesole present a focused overview of allogeneic transplantation for multiple myeloma. Additionally, this article addresses the challenges of allogeneic transplantation, including continued relapse and treatment-related toxicity and mortality.
Shortcomings of Current Therapy
Multiple myeloma remains an incurable disease despite advances in systemic therapy and supportive care. Although standard-dose chemotherapy provides palliative benefit, the median survival is approximately 29 months, and few patients achieve a complete remission. Randomized trials have demonstrated improved response rates, low toxicity, and increased survival with autologous transplant as consolidation, compared with standard chemotherapy. Tandem autologous transplants produce a superior complete remission rate compared to single transplants, but overall survival is equivalent (with the exception of patients with low beta-2-microglublin, in whom overall survival is improved). Nevertheless, relapse due to minimal residual disease continues to be the main reason for failure.
New insights into factors that control the growth and survival of plasma cells as well as their critical interaction with the microenvironment have led to innovative therapies with thalidomide (Thalomid), proteasome inhibitors, and bisphosphonates. While unlikely to cure myeloma, these agents offer the possibility of stabilizing minimal residual disease.
The current staging system for multiple myeloma groups patients into three categories based on paraprotein volume, skeletal lesions, and laboratory parameters. However, the highly variable clinical course of similarly staged patients underscores the need to revise this classification system.
Modification of the current system to incorporate such characteristics as chromosome 13 abnormalities and beta-2-microglobulin levels should provide the framework for a prognostic model to discriminate between low-, intermediate-, and high-risk patient groups. Gene expression profiles generated by DNA microarray analysis will likely emerge as a method to identify clinically relevant subsets among patients with otherwise indistinguishable myeloma.
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