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Multiple Myeloma

Multiple myeloma is a malignant proliferation of plasma cells. The tumor, its products, and the host response to it result in a number of organ dysfunctions and symptoms of bone pain or fracture, renal failure, susceptibility to infection, anemia, hypercalcemia.

Etiology The cause of myeloma is not known. Myeloma occurred with increased frequency in those exposed to the radiation of nuclear multiple myeloma.

Incidence And Prevalence About 14,400 cases of myeloma were diagnosed in 2006, and 10,400 people died from the disease. Myeloma increases in incidence with age. The median age at diagnosis is 68 years. It is rare under age 40.

Pathogenesis And Clinical Manifestations Bone pain is the most common symptom in myeloma, affecting nearly 70 percent of patients. The pain usually involves the back and ribs, and unlike the pain of metastatic carcinoma, which often is worse at night, the pain of myeloma is precipitated.

The next most common clinical problem in patients with myeloma is susceptibility to bacterial infections. The most common infections are pneumonias and pyelonephritis, and the most frequent pathogens are Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae in the lungs and Escherichia coli and other gram-negative organisms in the urinary tract. In about 25 percent of patients, recurrent infections are multiple.

Renal failure occurs in nearly 25 percent of myeloma patients, and some renal pathology is noted in over half. There are many contributing factors. Hypercalcemia is the most common cause of renal failure. Glomerular deposits of amyloid, hyperuricemia, recurrent infections.

Anemia occurs in about 80 percent of myeloma patients. It is usually normocytic and normochromic and related both to the replacement of normal marrow by expanding tumor cells and to the inhibition of hematopoiesis by factors made by the tumor. In addition, mild hemolysis may contribute to the anemia.

TREATMENT

About 10 percent of patients with myeloma will have an indolent course demonstrating only very slow progression of disease over many years. Such patients only require antitumor therapy when the serum myeloma protein level rises above 50 g/L (5 g/dL) or progressive bone lesions develop.

The vast majority of patients with myeloma require therapeutic intervention. In general, such therapy is of two sorts: systemic chemotherapy to control the progression of myeloma, and symptomatic supportive care to prevent serious morbidity from the complications of the disease. All patients with stage II or III disease and stage I patients exhibiting Bence Jones proteinuria, progressive lytic bone lesions, vertebral compression fractures, recurrent infections.

The standard treatment has consisted of intermittent pulses of an alkylating agent [L-phenylalanine mustard (L-PAM, melphalan), cyclophosphamide, or chlorambucil] and prednisone administered for 4 to 7 days every 4 to 6 weeks. The alkylating agents appear to be roughly equally active, but resistance to one agent is often accompanied by resistance to Melphalan is used most commonly, but because of their near equivalence in antitumor efficacy, we favor cyclophosphamide.

The ideal duration of therapy has not been determined. Most physicians treat every 4 to 6 weeks for 1 or 2 years. Cessation of therapy is followed by relapse, usually within a year. Retreatment may be associated with a second response in up to 80 percent of patients. Maintenance therapy (e.g., with IFNa) may prolong the duration of response, but this therapy is toxic and has generally not prolonged survival. The regrowth rate of the tumor during relapse accelerates with each relapse.

About 15 percent of patients die within the first 3 months after diagnosis, and subsequently, the death rate is about 15 percent per year. The disease usually follows a chronic course for 2 to 5 years before developing.