The Pathophysiology of Multiple Myeloma
A Malignancy of Marrow Plasma Cells With Overproduced Antibodies
Jul 26, 2008
Multiple myeloma is the cancerous growth of white blood cells called plasma cells. Although one might think of such a condition as a type of leukemia, multiple myeloma has a few unique features that tend to make the disease stand on its own. This requires an understanding of the disease process.
Pathophysiology
Plasma cells are mature forms of lymphocytes, a subclass of white blood cells responsible for providing the antibody component of the immune system. Plasma cells actively produce antibodies against certain pathogens. These cells, like all blood cells, are produced in the bone marrow.
In multiple myeloma, which may be due to radiation, benzene, or other chemical exposures, a specific plasma cell in the bone marrow becomes cancerous and grows uncontrollably, filling the inner spaces of the bone. This happens within the marrow of several bones, hence the term "multiple myeloma." Rarely, plasma cells flourish and fill the bloodstream in a variant of multiple myeloma called plasma cell leukemia.
These rapidly growing plasma cells produce antibodies in now excessive amounts. In fact, these antibodies are all of a specific type and are called monoclonal antibodies, because these cells are stemming from the same original plasma cell. Besides effects from overcrowding in the bone marrow, multiple myeloma also has clinical manifestations that result from monoclonal gammopathy, the presence of these monoclonal antibodies.
Clinical Manifestations
As a result of plasma cell overgrowth in the bone marrow, patients with multiple myeloma often complain of pain in areas such as the chest and back. They may also have fatigue because of inefficient production of red blood cells, infections because of inadequate circulating white blood cells, and proneness to bleeding and bruising because of a low blood platelet count. As for the monoclonal antibodies, they can form a protein deposit called amyloid, which can accumulate in peripheral nerves to produce neurological symptoms and in the kidneys to cause renal failure.
Laboratory Tests
Besides key findings on the patient history and physical examination, multiple myeloma requires several tests for diagnosis. X-rays of the entire skeleton reveal abnormalities where the myeloma is active. Blood tests will show low counts of red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia) as well as elevated blood calcium levels (hypercalcemia) due to bone destruction.
Two steps are important for diagnosis of multiple myeloma. One is electrophoresis, which finds excess protein in the blood from monoclonal antibodies and detects the light-chain component of these antibodies in urine, which is called Bence-Jones protein in this context. The other is a pathologist examination of bone marrow tissue following its aspiration from the bone itself..
Treatment
The treatment of multiple myeloma includes chemotherapy and bone marrow transplantation. Chemotherapeutic drugs to treat multiple myeloma are used in combination and include melphalan, prednisone, vincristine, carmustine, doxorubicin, cyclophosphamide, thalidomide, bortezomib, lenalidomide, and other agents. For bone marrow transplantation, this can be performed with marrow tissue from another person (allogeneic) or from the patient with extensive treatment of the tissue prior to reimplantation back into the patient (autologous).
Prognosis
Patients generally relapse after initial treatment for multiple myeloma. A variety of factors predict survival and are determined by particular serum, immunologic, and chromosomal studies.
References
- Rajkumar, S. Vincent. "Clinical and Laboratory Manifestations of Multiple Myeloma." In: Rose, Burton D., editor. UpToDate. Waltham, MA: UpToDate, 2008.
- Rajkumar, S. Vincent. "Diagnosis and Differential Diagnosis of Multiple Myeloma." In: Rose, Burton D., editor. UpToDate. Waltham, MA: UpToDate, 2008.
- Rajkumar, S. Vincent. "Treatment of Relapsed or Resistant Multiple Myeloma." In: Rose, Burton D., editor. UpToDate. Waltham, MA: UpToDate, 2008.
