Multiple Myeloma

 Multiple myeloma is caused by a neoplastic plasma cell that continually proliferates and produces a monoclonal antibody.  The clones of the neoplastic plasma cell proliferate in the bone marrow, disrupting hematopoiesis and causing extensive bone damage, and can lead to pathologic fractures, anemia, hypercalcemia, kidney damage, and occasionally blood hyperviscosity.  The cause of multiple myeloma is currently unknown.  The annual incidence of multiple myeloma in the U.S. is approximately 5 per 100,000.[1]  The disease is slightly more common in males and twice as common in blacks than whites.[2]  Multiple myeloma is most commonly diagnosed in the seventh decade of life.[3]

The signs and symptoms of multiple myeloma may include bone pain induced by movement, usually in the back or chest, weakness, pallor, fatigue, weight loss, radiculopathy, and cord compression.

The diagnosis can be suspected by correlating the above signs and symptoms with radiographic imaging, increased serum or urinary protein, the presence of Bence Jones proteins in the urine, and serum protein electrophoresis with immunostaining for increased paraprotein, but is typically confirmed by bone marrow biopsy.  A metastatic bone survey with plain radiographs including the humerus and femur should be performed in all patients suspected of having multiple myeloma in order to identify the extent of their disease.  The Mayo Clinic and the International Myeloma Working Group have established three criteria which all must be met for the diagnosis ofmultiple myeloma: the presence of M-protein in serum or urine, a bone marrow biopsy containing more than ten percent clonal plasma cells, and the presence of organ or tissue dysfunction.[4,5]

The prognosis for patients with multiple myeloma can be determined by the International Stageing System using only levels of beta-2 microglobulin (B2M) and serum albumin.  Stage 1 is defined as B2M less than 3.5 mg/L and serum albumin greater than or equal to 3.5 g/dL.  Stage 2 is neither stage 1 or 3.  Stage 3 is B2M greater than or equal to 5.5 mg/L.  Those with stage 1 disease have a median survival of 62 months, stage 2 have a median survival of 45 months, and stage 3 have a median survival of 29 months.[6]  Cytogenetic analysis may provide further prognostic clues with chromosome 13 deletion and non-hyperdiploidy associated with a poorer prognosis.[7]

Treatment is commonly a chemotherapeutic regiment including combinations of dexamethasone, thalidome, cyclophosphamide, vincristine, and adriamycin.  Plasmapheresis can treat hyperviscosity syndrome from the hyperproteinemia.  Allogeneic stem cell transplant is currently an experimental therapy that offers the possibility of a cure, but has a high mortality associated with the procedure.