Chapter 106. Plasma Cell Disorders (Part 3)

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Incidence and Prevalence About 19,900 cases of myeloma were diagnosed in 2007, and 10,790 people died from the disease in the United States. Myeloma increases in incidence with age. The median age at diagnosis is 68 years; it is uncommon under age 40. The yearly incidence is around 4 per 100,000 and remarkably similar throughout the world. Males are more commonly affected than females, and blacks have nearly twice the incidence of whites. Myeloma accounts for ~1% of all malignancies in whites and 2% in blacks; 13% of all hematologic cancers in whites and 33% in blacks. The incidence of...

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Chapter 106. Plasma Cell Disorders (Part 3) Incidence and Prevalence About 19,900 cases of myeloma were diagnosed in 2007, and 10,790 people died from the disease in the United States. Myeloma increases in incidence with age. The median age at diagnosis is 68 years; it is uncommon under age 40. The yearly incidence is around 4 per 100,000 and remarkably similar throughout the world. Males are more commonly affected than females, and blacks have nearly twice the incidence of whites. Myeloma accounts for ~1% of all malignancies in whites and 2% in blacks; 13% of all hematologic cancers in whites and 33% in blacks. The incidence of myeloma is highest in African-American and Pacific islanders; intermediate in Europeans and North American Caucasians; and lowest in developing countries including Asia. The higher incidence in more developed countries may result from the combination of a longer life expectancy and more
frequent medical surveillance. Incidence of multiple myeloma in other ethnic groups including native Hawaiians, female Hispanics, American Indians from New Mexico, and Alaskan natives is higher relative to U.S. Caucasians in the same geographic area. Chinese and Japanese populations have a lower incidence than Caucasians. Immunoproliferative small intestinal disease with alpha heavy chain disease is most prevalent in the Mediterranean area. Despite these differences in prevalence, the characteristics, response to therapy, and prognosis of myeloma are similar worldwide. Pathogenesis and Clinical Manifestations (Table 106-1) Multiple myeloma (MM) cells bind via cell-surface adhesion molecules to bone marrow stromal cells (BMSCs) and extracellular matrix (ECM), which triggers MM cell growth, survival, drug resistance, and migration in the bone marrow milieu (Fig. 106-3). These effects are due both to direct MM cell– BMSC binding and to induction of various cytokines including IL-6, insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and stromal cell–derived growth factor (SDF)-1α. Growth, drug resistance, and migration are mediated via Ras/Raf/mitogen-activated protein kinase, PI3-K/Akt, and protein kinase C signaling cascades, respectively.
Figure 106-3 Pathogenesis of multiple myeloma. Multiple myeloma cells interact with bone marrow stromal cells and extracellular matrix proteins via adhesion molecules, triggering adhesion-mediated signaling as well as cytokine production. This triggers cytokine-mediated signaling that provides growth, survival, and anti- apoptotic effects as well as development of drug resistance. HSP, heparin sulfate proteoglycan. Table 106-1 Clinical Features of Multiple Myeloma
Clinical Finding Underlying Cause and Pathogenetic Mechanism Hypercalcemia, Tumor expansion, production of osteoclast osteoporosis, pathologic activating factor by tumor cells, osteoblast fractures, lytic bone lesions, inhibitory factors bone pain Renal failure Hypercalcemia, light chain deposition, amyloidosis, urate nephropathy, drug toxicity (nonsteroidal anti-inflammatory agents, bisphosphonates), contrast dye Easy fatigue—anemia Bone marrow infiltration, production of inhibitory factors, hemolysis, decreased red cell production, decreased erythropoietin levels Recurrent infections Hypogammaglobulinemia, low CD4 count, decreased neutrophil migration
Neurologic symptoms Hyperviscosity, cryoglobulinemia, amyloid deposits, hypercalcemia, nerve compression, anti- neuronal antibody, POEMS syndrome, therapy- related toxicity Nausea and vomiting Renal failure, hypercalcemia Bleeding/clotting Interference with clotting factors, antibody disorder to clotting factors, amyloid damage of endothelium, platelet dysfunction, antibody coating of platelet, therapy-related hypercoagulable defects Note: POEMS, polyneuropathy, organomegaly, endocrinopathy, multiple myeloma, and skin changes.