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Clinical Description
Multiple myeloma is a cancer of the plasma cell, a type of lymphocyte that produces antibodies, proteins that normally fight infections. These abnormal plasma cells proliferate and accumulate in the marrow, thereby interfering with normal bone marrow function. Furthermore, instead of producing normal, fully formed antibodies to fight infections like normal plasma cells do, these abnormal plasma cells secrete abnormally large amounts of a single type of protein (“monoclonal immunoglobulin”) derived from one cell population (“monoclonal”). The plasma cells continuously make these proteins, which are in turn excreted by the kidneys. These proteins may directly harm the kidney, or deposit in the kidneys and cause kidney disease. Lastly, these abnormal myeloma cells also produce chemicals that stimulate other cells to dissolve bone. This causes bones to develop “holes”, or lytic lesions.
There are several types of myeloma. Most cases have multiple marrow sites and the term “multiple myeloma” is used. Solitary myeloma is when only one site is evident, localized myeloma when there are a few nearby sites, and extramedulluary myeloma is when tissues other than marrow are involved. Tumors of plasma cells are known as plasmacytomas.
Symptoms of Multiple Myeloma
Since multiple myeloma often involves bone lesions, the most common early symptom of multiple myeloma is bone pain, which usually occurs in the lower back or ribs but may involve any bone. The bony lesions release calcium from the bone into the blood, and can cause high calcium levels. Since the abnormal plasma cells in multiple myeloma produce proteins in an uncontrolled manner which can cause kidney dysfunction, patients may experience symptoms of kidney failure, such as fatigue, decreased urination and swelling of the feet.
Since multiple myeloma involves abnormal plasma cells that accumulate and crowd out the normal marrow, patients may have a marrow that does not function properly. This leads to patients having low red blood cell levels (anemia), and low levels of white blood cells and platelets. Such patients can experience fatigue, weakness and shortness of breath on exertion due to anemia. When the white blood cells (which fight infection) are too low, patients may experience recurrent infections. When the platelets (which clot blood) become too low, patients may experience easy bruising, nose or gum bleeding and coughing up blood, or blood in the stool or urine.
Risk Factors of Multiple Myeloma
Myeloma rarely occurs in people younger than 40 yrs. Most cases occur after age 60. African-Americans have a higher rate of myeloma. Previous radiation and chemotherapy has not been shown to cause myeloma.
How Multiple Myeloma is Diagnosed
Multiple myeloma can be diagnosed by examining the blood, urine and the bone marrow, and by X-rays of the skeleton. The diagnosis of multiple myeloma depends on finding increased bone marrow myeloma cells (malignant plasma cells) by bone marrow aspiration and biopsy, and either increased “monoclonal” proteins (“M” component) in the blood/urine, or bony lesions on X-ray.
Other simple tests may aid as well. Blood cell counts are measured and may show low red blood, white blood and platelet cell counts, showing the degree which to bone marrow is affected. Calcium due to bone destruction can be high, and the protein albumin may be low. Beta-2 microglobulin is a protein that is an indirect measure of the size and growth rate of myeloma. Lastly, kidney function is determined by blood tests.
Treatment Options for Multiple Myeloma at Tufts Medical Center
Patients should first be evaluated by a specialist to determine the stage of myeloma. Some patients with a mild elevation of the paraprotein in the blood can be closely followed. Their disease may never turn into myeloma. This disorder is called MGUS, which stands for “Monoclonal Gammopathy of Undetermined Significance”. Patients with MGUS have an increased risk of eventually progressing to myeloma.
For the majority of patients, myeloma cannot be cured, so the goal of treatment is to prolong survival and alleviate symptoms. For more severe forms or myeloma, therapy with combinations of several drugs has been the mainstay. A specialist should determine if traditional drugs such as melphalan and dexamethasone or newer drugs such as lenalidomide (Revlimid) and/or bortezomib (Velcade) are appropriate. Most patients, even when they are older (up to 80 years), should be considered for an autologous stem cell transplant when the myeloma is at a minimal stage following initial therapy. The stem cells are collected from the patient by a process called leukapheresis and returned to him/her after a round of high dose chemotherapy. This treatment is generally well-tolerated and can keep the myeloma in a remission for a number of years. In some patients this transplant can be repeated when the disease comes back.
Another option especially for younger patients is to get a stem cell transplant from a sibling or unrelated donor. These “standard of care” therapies are all available at Tufts Medical Center. The Stem Cell Transplant program at Tufts also offers a novel treatment with a radioactively labeled monoclonal antibody (Zevalin) that is given to eligible patients, where the goal is to eliminate the stem cell that causes myeloma.
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