multiple myeloma- Notes

[Anonymous]

Multiple myeloma is a plasma cell cancer in which a clone of abnormal plasma cells multiplies, forms tumors in the bone marrow, and produces a large quantity of abnormal antibodies that accumulate in the blood or urine.

In the United States, multiple myeloma accounts for about 1 percent of all cancers; about 12,500 new cases are diagnosed every year. This uncommon cancer affects men and women equally and usually is seen in people over 40 years old. Its cause is unknown.

Plasma cell tumors (plasmacytomas) are most common in the pelvic bones, spine, ribs, and skull. Occasionally, they develop in areas other than bones, particularly in the lungs and reproductive organs.

The abnormal plasma cells almost always produce a large quantity of abnormal antibodies, and the production of normal antibodies is reduced. As a result, people who have multiple myeloma are especially susceptible to infections.

Pieces of the abnormal antibodies frequently end up in the kidneys, damaging them and sometimes causing kidney failure. Deposits of antibody pieces in the kidneys or other organs can lead to amyloidosis, (see page 690 in Chapter 142, Amyloidosis) another serious disorder. Abnormal antibody pieces in the urine are called Bence Jones proteins.

Symptoms and Diagnosis
Sometimes multiple myeloma is diagnosed before a person has any symptoms--for instance, when an x-*** performed for other reasons reveals punched-out areas in the bones that are typical of this disorder.

Multiple myeloma often causes bone pain, especially in the spine or ribs, and weakens bones, which may fracture easily. Although bone pain is usually the first symptom, occasionally the disorder is diagnosed only after anemia (too few red blood cells), recurring bacterial infections, or kidney failure develops. Anemia results when the abnormal plasma cells crowd out the normal cells that produce red blood cells in the bone marrow. Bacterial infections result because abnormal antibodies are ineffective against infections. Kidney failure results when pieces of the abnormal antibodies (Bence Jones proteins) damage the kidneys.

In rare instances, multiple myeloma interferes with blood flow to the skin, fingers, toes, and nose because the blood thickens (hyperviscosity syndrome). Inadequate flow of blood to the brain can result in neurologic symptoms, such as confusion, visual problems, and headaches.

Several blood tests may help a doctor diagnose this disorder. A complete blood cell count may detect anemia and abnormal red blood cells. Usually, the erythrocyte sedimentation rate, a test that measures how quickly red blood cells (erythrocytes) settle to the bottom of a test tube, is abnormally high. Calcium levels are abnormally high in one third of the people who have this disorder because changes in the bone result in calcium leaking into the bloodstream. However, the key diagnostic tests are serum protein electrophoresis and immunoelectrophoresis, blood tests that detect and identify the abnormal antibody that's the telltale sign of multiple myeloma. This antibody is found in about 85 percent of the people who have this disorder. Also, urine electrophoresis and immunoelectrophoresis can detect Bence Jones proteins, which are found in 30 to 40 percent of the people who have multiple myeloma.

Often, x-rays show loss of bone density (osteoporosis) and punched-out areas of bone destruction. A bone marrow biopsy, in which a sample of marrow is obtained with a needle and syringe and examined under a microscope, shows a large number of plasma cells abnormally arranged in sheets and clusters; the cells also may appear abnormal.

Treatment
Treatment is aimed at preventing or relieving symptoms and complications, destroying abnormal plasma cells, and slowing progression of the disorder.

Strong analgesics and radiation therapy directed at the affected bones can help relieve bone pain, which can be severe. People who have multiple myeloma, especially with Bence Jones proteins in the urine, need to drink plenty of fluids to dilute the urine and help prevent dehydration, which can make kidney failure more likely. Staying active is important; prolonged bed rest tends to accelerate osteoporosis and make the bones more vulnerable to fractures. However, running and heavy lifting should be avoided because the bones are weakened.

People who have signs of infection--fever, chills, or reddened areas of the skin--should see a doctor promptly because they may need antibiotics. Those who have severe anemia may need red blood cell transfusions, although for some, erythropoietin--a drug that stimulates red blood cell formation--may adequately treat the anemia. High calcium levels in the blood can be treated with prednisone and intravenous fluids and sometimes with diphosphonates, drugs that lower calcium levels. People who have high levels of uric acid in the blood may benefit from allopurinol.

Chemotherapy slows the progression of multiple myeloma by killing the abnormal plasma cells. The drugs most frequently used are melphalan and cyclophosphamide. 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. Corticosteroids such as prednisone or dexamethasone are also given as part of the chemotherapy. For those who have a good response to chemotherapy, the drug interferon may enable the response to last longer.

High-dose chemotherapy combined with radiation therapy is still experimental. Because this combination is so toxic, stem cells must be collected from a person's blood or bone marrow before treatment; these cells are then returned (transplanted) to the person after treatment. Generally, this procedure is reserved for people who are under 50 years old.

Currently, no cure is available for multiple myeloma. However, treatment slows its progress in more than 60 percent of its victims. Those who respond to chemotherapy can expect to live for 2 to 3 years after the disorder is diagnosed, sometimes much longer. Occasionally, people who survive for many years after successful treatment of multiple myeloma develop leukemia or fibrous tissue (scarring) in the bone marrow. These late complications may result from chemotherapy and often lead to severe anemia and an increased susceptibility to infections.

Macroglobulinemia
Macroglobulinemia (Waldenström's macroglobulinemia) is a disorder in which plasma cells produce an excessive quantity of macroglobulins (large antibodies) that accumulate in the blood.

Macroglobulinemia results from a group (clone) of abnormal, cancerous lymphocytes and plasma cells. Men are affected more often than women, and the average age at which the disorder appears is 65 years. Its cause is unknown.

Symptoms and Diagnosis
Many people who have macroglobulinemia have no symptoms. Others, whose blood has thickened (hyperviscosity syndrome) because of the large quantity of macroglobulins, have reduced blood flow to the skin, fingers, toes, and nose as well as a variety of other symptoms. These symptoms include abnormal bleeding from the skin and mucous membranes (such as the lining of the mouth, nose, and intestinal tract), fatigue, weakness, headache, dizziness, and even coma. The thickened blood also may aggravate heart conditions and cause increased pressure in the brain. Tiny blood vessels in the back of the eyes can become engorged and may bleed, resulting in damage to the retina and impaired eyesight.

People who have macroglobulinemia may also have swollen lymph nodes, rashes, an enlarged liver and spleen, recurring bacterial infections, and anemia.

Macroglobulinemia often produces cryoglobulinemia, a condition characterized by cryoglobulins, which are abnormal antibodies that precipitate (form solid particles) in the blood when cooled below body temperature and dissolve when warmed. People who have cryoglobulinemia may become very sensitive to cold or develop Raynaud's phenomenon, in which the hands and feet become very painful and turn white when they're exposed to cold.

Blood tests detect abnormalities in people who have macroglobulinemia. The number of red and white blood cells and platelets may be abnormally low, and the erythrocyte sedimentation rate, which measures how quickly red blood cells (erythrocytes) settle to the bottom of a test tube, usually is abnormally high. Blood clotting test results may be abnormal, and other tests may detect cryoglobulins. Bence Jones proteins (pieces of abnormal antibodies) may be found in the urine. But the most useful diagnostic tests are serum protein electrophoresis and immunoelectrophoresis, which detect the large quantity of abnormal macroglobulins in a blood sample.

X-rays may show a loss of bone density (osteoporosis). A bone marrow biopsy, in which a sample of marrow is obtained with a needle and syringe and examined under a microscope, may reveal an increased number of lymphocytes and plasma cells, which helps confirm the diagnosis.

Prognosis and Treatment
The course of the disorder varies from person to person. Even without treatment, many people survive for 5 years or more.

A person whose blood is thickened must be treated promptly with plasmapheresis, a procedure in which blood is withdrawn, the abnormal antibodies are removed from it, and the red blood cells are returned to the person. Chemotherapy, usually with chlorambucil, can slow the growth of abnormal plasma cells but doesn't cure macroglobulinemia. Alternatively, melphalan or cyclophosphamide may be used as well as various other drugs, alone or in combinations.