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| Multiple myeloma (also known simply as myeloma or plasma cell myeloma) is a hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. Although it initially develops in the bone marrow, it spreads to the peripheral blood, lymph nodes and other organs. Its prognosis despite therapy is generally poor. |
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Signs and symptoms
Symptoms can include: malaise, anemia, infections (due to decreased immunity) and fractures (due do breakdown of bone by malignant cells). Often, the diagnosis of multiple myeloma is made incidentally during routine blood tests for other conditions. Osteoporosis is often present in an accelerated form in myeloma patients.
Diagnosis
The existence of unexplained anemia, a high erythrocyte sedimentation rate (ESR) and a high serum protein (especially raised globulin) may suggest further testing. A doctor will then order protein electrophoresis, on which a paraprotein band can be noticed. Quantitative measurements of the paraprotein are necessary to determine the seriousness of the disease. The paraprotein is a deviant immunoglobulin produced by the tumour clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins). In theory, myeloma can produce all classes of immunoglobulin, but IgE and IgD myeloma are very rare.
Additional findings are: a raised calcium (when myeloma cells are breaking down bone, releasing calcium into the bloodstream) and decreased renal function (due to amyloid of the kidney).
A bone marrow biopsy is required for a complete diagnosis. This shows over 10% plasma cells. Immunohistochemistry can confirm the plasma cell character of uncertain cells. Cytogenetics is generally not performed in myeloma, although particular abberations have been reported (see below).
Types
There are at least two forms of myeloma:
* Secretory - where enzymes are released that allow blood testing for diagnosis and progression monitoring.
* Non-secretory - where enzymes are not released and are thus not available for blood testing. Progression in these cases is monitored through bone marrow biopsy. It is rare compared to the secretory forms.
Related conditions are solitary plasmacytoma (a single tumor of plasma cells producing antibodies, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g. amyloidosis) and monoclonal gammopathy of unknown significance (MGUS).
Pathophysiology
The accepted theory is that myeloma develops when a chromosomal translocation occurs between the immunoglobulin heavy chain gene (on the fourteenth chromosome) and a gene that produces an oncogene. The result is proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations.
Production of cytokines by the plasma cells causes much of their localised damage, such as osteoporosis. In contrast, the antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other myeloma-associated symptoms.
Epidemiology
There are approximately 45,000 people in the United States living with multiple myeloma, and the American Cancer Society estimates that approximately 14,600 new cases of myeloma are diagnosed each year in the United States.
Multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset.
Multiple myeloma affects slightly more men than women. African Americans and Native Pacific Islanders have the highest reported incidence of this disease and Asians the lowest. Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans, myeloma is one of the top 10 leading causes of cancer death.
Treatment
Treatment for multiple myeloma is focused on disease containment and suppression, as no reliable cure has been found.
Some of these treatments are:
* thalidomide with steroids
* chemotherapy regimens:
o vincristine, adriamycin (doxorubicin) and dexamethasone (abbreviated VAD).
o high-dose chemotherapy (melphalan) with stem cell transplant
o low-dose therapy with melphalan (essentially palliative)
* immunotherapy with bortezimib
Chemotherapy and stem-cell transplants are generally only administered to patients who can tolerate these (potentially toxic) treatments.
History
In some countries multiple myeloma is referred to as "Kahler's (http://www.whonamedit.com/synd.cfm/1595.html) disease", after the Austrian internist Otto Kahler (1849-1893).
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Multiple myeloma". |
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