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Myeloma is a malignancy of terminally differentiated B cells (plasma cells) that produces a complete and/or partial (light chain) monoclonal immunoglobulin protein. 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 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. Prognosis has been correlated with serum levels of β2-microglobulin shed from the surface of myeloma cells and C-reactive protein, reflecting endogenous interleukin-6 activity, and with the myeloma cell labeling-index. The molecular analysis of myeloma, using gene expression profiling and other genetic techniques, indicates that myeloma is a heterogeneous disorder comprising at least 7 subentities. Gene expression profiling can identify 15 percent of patients with very aggressive myeloma who have a poor outcome with all current therapies. The immunomodulatory drugs, thalidomide and lenalidomide, and the proteasome inhibitor bortezomib have demonstrated the ability to ameliorate advanced and otherwise refractory disease, by cotargeting both myeloma and stromal cell components, and are now used in combination with melphalan and prednisone as initial therapy. Melphalan-based autologous hematopoietic stem cell transplantation (auto-HSCT) in combination with novel agent can achieve remarkable results in patients with good risk myeloma as defined by favorable gene expression profiles. Such patients can achieve a 10-year survival, exceeding 60 percent of patients. The duration of complete remission in these patients has been sustained, raising the hope that some of these patients are cured.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: auto-HSCT, autologous hematopoietic stem cell transplantation; β2M, β2-microglobulin; CT, computed tomography; del, deletion; FDG, fluorodeoxyglucose; FISH, fluorescence insitu hybridization; GVHD, graft-versus-host disease; GVM, graft-versus-myeloma effect; ISS, International Staging System; LCDD, light-chain deposition disease; MIP, macrophage inflammatory protein; MP, melphalan-prednisone; MRI, magnetic resonance imaging; PET, positron emission tomography; SCID, severe combined immunodeficiency; TGF-β, transforming growth factor-β; VTE, venous thromboembolism.

Myeloma accounts for approximately 1 percent of all malignancies and 10 percent of hematologic tumors, representing the second most frequently occurring hematologic malignancy in the United States.1 At any one time, 50,000 people suffer from myeloma, and approximately 15,000 cases are diagnosed ...

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