Multiple Myeloma
Multiple myeloma is a cancer of plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body.
Typically, multiple myeloma occurs in people at least 60 years of age. Although its cause is not certain, the increased occurrence of multiple myeloma among close relatives indicates that heredity plays a role. Exposure to radiation is thought to be a possible cause, as is exposure to benzene and other solvents. A herpesvirus, HHV-8, may play some role in the disease.
Normally, plasma cells make up less than 1% of the cells in the bone marrow; in multiple myeloma, typically the vast majority of bone marrow elements are cancerous plasma cells. The overabundance of these cancerous plasma cells in the bone marrow leads to the increased production of proteins that suppress the development of other normal bone marrow elements, including white blood cells, red blood cells, and platelets (cell-like particles that help the body form blood clots). In addition, the abnormal plasma cells almost always produce a large amount of a single type of antibody accompanied by a markedly reduced amount of all other types of normal antibodies.
Often, collections of cancerous plasma cells develop into tumors that lead to loss of bone, most commonly in the pelvic bones, spine, ribs, and skull. Infrequently, these tumors develop in areas other than bone, particularly in the lungs, liver, and kidneys.
Symptoms and Complications
Because plasma cell tumors often invade bone, bone pain, often in the back, ribs, and hips, may occur. Loss of bone density (osteoporosis) resulting from plasma cell tumors weakens bones, which can lead to fractures. In addition, calcium released from the bones may result in abnormally high levels of calcium in the blood, possibly causing constipation, increased frequency of urination, weakness, and confusion.
The reduced production of red blood cells often leads to anemia, which causes fatigue, weakness, and pallor, and may lead to heart problems. Decreased production of white blood cells leads to repeated infections, which may cause fever and chills. Decreased platelet production impairs the blood's ability to clot and results in easy bruising or bleeding.
Pieces of monoclonal antibodies, known as light chains, frequently end up in the collecting system of the kidneys, sometimes permanently damaging them by interfering with their filtering function and leading to kidney failure. The light chain pieces of the antibody in the urine (or blood) are called Bence Jones proteins. The increased number of growing cancerous cells can lead to the overproduction and excretion of uric acid in the urine, which can lead to kidney stones. Calcium levels may become high, affecting the heart, kidneys, and brain. Deposits of certain types of antibody pieces in the kidneys or other organs can lead to amyloidosis (see Section 25, Chapter 304), another serious disorder found in a small number of people with multiple myeloma.
In rare instances, multiple myeloma interferes with blood flow to the skin, fingers, toes, nose, kidneys, and brain because the blood thickens (hyperviscosity syndrome (see Section 14, Chapter 175)).
Diagnosis
Multiple myeloma may be discovered even before a person has symptoms, when an x-ray performed for another reason shows a loss of bone density. Bone loss may be widespread or limited to scattered punched-out areas of a few bones.
Multiple myeloma is sometimes suspected because of symptoms, such as back pain or other sites of bone pain, fatigue, fevers, and bruising. Blood tests performed to investigate such symptoms may reveal that a person has anemia, a decreased white blood cell count, a decreased platelet count, or kidney failure.
The two most useful blood tests are serum protein electrophoresis and immunoelectrophoresis. They detect and identify an overabundance of a single type of antibody found in most people who have multiple myeloma. Doctors also measure the different types of antibodies, especially IgG, IgA, and IgM.
Calcium levels are usually measured as well. A 24-hour collection of urine is analyzed for the amount and types of protein in it. Bence Jones proteins are found in the urine of half of the people who have multiple myeloma.
A bone marrow biopsy (see Section 14, Chapter 170) is almost always performed to confirm the diagnosis. When a person has multiple myeloma, the biopsy shows a large number of plasma cells abnormally arranged in sheets and clusters; the individual cells also may appear abnormal.
In addition, other blood tests are useful in determining the overall outlook for the person. Higher levels of beta2-microglobulin and C-reactive protein in the person's blood when the disease is diagnosed usually indicate the likelihood of a shortened survival and are likely to affect treatment decisions.
Treatment and Prognosis
Multiple myeloma remains incurable despite recent advances in therapy. Treatment is aimed at preventing or relieving symptoms and complications, destroying abnormal plasma cells, and slowing progression of the disorder.
The most consistently helpful group of drugs for multiple myeloma is corticosteroids, such as prednisone or dexamethasone. In addition, chemotherapy slows the progression of multiple myeloma by killing the abnormal plasma cells. Because chemotherapy kills normal cells as well as abnormal ones, the blood cells are monitored and the dose is adjusted if the number of normal white blood cells and platelets decreases too much. Melphalan, and less often cyclophosphamide, are the chemotherapy drugs most often added to corticosteroids. Vincristine and doxorubicin are also effective and may have less severe side effects, particularly on the bone marrow, than melphalan and cyclophosphamide. Thalidomide may help nearly one third of people whose multiple myeloma is worsening with other treatments. For people who have a good response to chemotherapy, the drug interferon may prolong the response somewhat but has little impact on survival.
Many new combinations of treatment are being used. One involves several months of conventional chemotherapy followed by high-dose chemotherapy. Because this high-dose treatment is also toxic to normal blood cells made in the bone marrow, stem cells (unspecialized cells that transform into immature blood cells, which eventually mature to become red blood cells, white blood cells, and platelets) are collected from the person's blood before the high-dose chemotherapy is administered. These stem cells are then returned (transplanted) to the person after the high-dose treatment (see Section 16, Chapter 187). Generally, this procedure is reserved for people who are younger than 70.
Strong analgesics and radiation therapy directed at the affected bones can help relieve bone pain, which can be severe. Radiation therapy may also prevent the development of fractures. Monthly intravenous administration of pamidronate (a bisphosphonate) and the more potent drug zoledronic acid can reduce the development of bony complications, and most people with multiple myeloma receive these drugs as part of their treatment forever. Staying active is also important; prolonged bed rest tends to accelerate bone loss and makes the bones more vulnerable to fractures. Most people can enjoy a normal lifestyle that includes most activities. Drinking plenty of fluids dilutes the urine and helps prevent dehydration, which can make kidney failure more likely.
People who have signs of infection--fever, chills, cough productive of sputum, or reddened areas of the skin--should seek attention from a doctor promptly because they may need antibiotics. Those who have severe anemia may need transfusions of red blood cells. Erythropoietin or darbepoietin, drugs that stimulate red blood cell formation, may adequately treat the anemia in some people. High levels of calcium in the blood can be treated with intravenous fluids and often require intravenous bisphosphonates. People who have high levels of uric acid in the blood may benefit from allopurinol, a drug that blocks the body's production of uric acid.
Currently, no cure is available for multiple myeloma. However, treatment slows disease progression in more than 60% of people. The average survival is more than 3 years after the disorder is diagnosed, but survival time varies widely depending on the features at the time of diagnosis and the response to treatment. Importantly, bisphosphonates to reduce bony complications, substances that stimulate the production of blood cells (growth factors) to increase the number of red and white blood cells, and better pain relievers have greatly improved the quality of life of these people. Occasionally, people who survive for many years after successful treatment of multiple myeloma develop leukemia or irreversible loss of bone marrow function. These late complications may result from chemotherapy and often lead to severe anemia and an increased susceptibility to infections and bleeding.
Because multiple myeloma is ultimately fatal, people with multiple myeloma are likely to benefit from discussions of end-of-life care that involve their doctors and appropriate family and friends. Points for discussion may include advance directives (see Section 1, Chapter 9), the use of feeding tubes, and pain relief (see Section 1, Chapter 8).
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