Definition of Multiple Myeloma
Multiple Myelomais a malignancy of terminally differentiated B cells (plasma cells) that produces a complete and/or partial (light chain) monoclonal immunoglobulin protein. Multiple Myeloma cells induce, in the context of the extracellular matrix, critical alterations in the marrow microenvironment, which, in turn, evoke cell-survival signals, contributing to resistance to therapy of this genomically complex and generally hypoproliferative tumor. The disease causes clinical symptoms by way of tumor mass effects (e.g., cord compression), cytokine production (e.g., anemia), bone destruction (e.g., pain), protein deposition in visceral organs (e.g., kidney and heart), and immunosuppression (e.g., infection).
Clinical manifestations of Multiple Myeloma
Clinical manifestations of Multiple Myeloma vary as a result of the heterogeneous biology, spanning the entire spectrum from indolent to highly aggressive disease with extramedullary features. Magnetic resonance imaging has become an important tool with which to stage the disease and to distinguish solitary plasmacytoma of bone from myeloma and, within the latter category, to document the extent and pattern of marrow involvement, which can be diffuse, micronodular, or macrofocal. Fluorodeoxyglucose positron emission tomography permits functional metabolic imaging of the entire body and, hence, detection of both intramedullary and extramedullary myeloma lesions.
Treatment of Multiple Myeloma with stem cell transplant
Autologous stem cell transplant within the first year of initiating treatment has been the standard of care for patients younger than 70 years of age with newly diagnosed myeloma. Although neither chemotherapy nor autologous stem cell transplant produces a cure, event-free and overall survival were prolonged following autologous stem cell transplant when compared to treatment with conventional chemotherapy alone.
Yet with the incorporation of the new chemotherapeutic agents (e.g., bortezomib, thalidomide, lenalidomide) as initial therapy, the response rate for patients with advanced stage Multiple Myeloma has improved and survival with chemotherapy alone is improving. Whether the use of these newer agents, alone or in combination, will delay or possibly even eliminate the need for stem cell transplant in patients with Multiple Myeloma is not known. In addition, survival with stem cell transplant is improving for certain populations with the incorporation of double (tandem) autologous stem cell transplant.
Consequently, the use of tandem transplantation is currently being compared to autologous transplantation followed by reduced-intensity conditioning allogeneic transplantation in patients with myeloma through the U.S. Clinical Trials Network.