Multiple myeloma

Definition

Multiple myeloma is a disorder in which plasma cells are produced in an uncontrolled and invasive (malignant) fashion.

Description

Plasma cells develop from lymphocytes, a type of white blood cell. They are found primarily in the bone marrow and lymph nodes. The marrow is located in spaces within the bones, especially within the sternum (breast bone), spine, ribs, skull, pelvic bones, and the long bone of the thigh. Bone marrow is a very active tissue that is responsible for producing the different cells that circulate in blood. These include red blood cells, platelets, and the many types of white blood cells.

Plasma cells are responsible for helping the body fight infection. They produce substances called antibodies (also called immunoglobulins). Antibodies circulate within the blood and recognize markers, called antigens, on the cells of invading organisms (like bacteria). These antibodies have a variety of functions, all of which ultimately serve the purpose of defending the body against invading organisms.

Multiple myeloma occurs when the plasma cells in the bone marrow begin reproducing uncontrollably. While normal bone marrow contains less than 5% plasma cells, bone marrow in a patient with multiple myeloma contains over 10% plasma cells.

Multiple myeloma tends to be a disease of the elderly. The average patient is 68 years old when diagnosed. During the last 10 years, doctors have seen an increase in cases of multiple myeloma occurring at younger ages, but patients are usually over age 40. Men have a slightly increased chance of having multiple myeloma, and African-Americans are twice as likely as caucasians to develop the disease. Worldwide, the disease rates are about the same, with approximately four people in 100,000 developing multiple myeloma.

Although the exact cause of multiple myeloma has not been determined, researchers believe that there may be a link between exposure to certain environmental substances and the development of multiple myeloma. This is based on several observations:

• About 20 years after World War II, there was an increased incidence in multiple myeloma among people who had been exposed to the radiation in nuclear warheads.
• There is an increased incidence of multiple myeloma among people who farm, and among those who work with wood, leather, and petroleum products.

Causes & symptoms

Bone pain is an extremely common symptom among patients with multiple myeloma. About 70% of all patients will report bone pain as their first symptom. This pain is due to several different processes. Plasma cells grow in number within the bone marrow, replacing normal marrow and putting pressure on the bone containing the marrow. Plasma cells also produce chemicals called osteoclast activating factors (OAF). OAF encourage special cells called osteoclasts to break down bone. This is a normal process, which should be balanced by the building up of new bone by cells called osteoblasts. In multiple myeloma, however, excess OAF are produced, upsetting the normal process called bone remodeling. Bone is eaten away by these overly active osteoclasts. Bones become weak (causing osteoporosis) and may even break (causing pathologic fractures).

The antibodies that are over produced in multiple myeloma function abnormally. Furthermore, other types of antibodies are under produced. Destruction of circulating antibodies also increases. This results in an increased chance of developing serious bacterial infections. The most common types of infections include pneumonia and kidney infections (pyelonephritis).

Abnormalities in the structure and function of kidney cells are extremely common in multiple myeloma. About half of all patients have these types of kidney problems. These problems occur because of several reasons, including:

• High levels of calcium in the blood (due to bone breaking down)
• Increased kidney infections
• Amyloidosis, a disease where protein deposits build up in organs and tissues in the body
• Increased circulating uric acid
• Exposure of kidney structures to very large amounts of the broken down products of antibodies. Furthermore, the blood in multiple myeloma may become thick and sludgy (referred to as hyperviscosity) due to the large amount of circulating protein from antibodies. This sludge may clog the delicate tubal system within the kidneys, causing damage or kidney failure.

A number of other problems are common in multiple myeloma. Because plasma cells take up space within the bone marrow, other cells normally produced there decrease and are sometimes defective in shape and function. Red blood cells decrease, resulting in anemia in about 80% of all people with multiple myeloma. Circulating antibodies may interfere with clotting, resulting in an increased risk of bleeding. The abnormally thick blood may interfere with blood circulation anywhere in the body, resulting in Raynaud's phenomenon. This circulation problem is particularly common in the fingers, toes, ears, and nose. Hyperviscosity may also cause headache, fatigue, and vision problems. Excess calcium in the blood may cause patients to feel weak, depressed, and confused. Sometimes, the plasma cells create a tumor called a plasmacytoma. Plasmacytomas may press on bone, causing fractures. Fractured bones may place unusual pressure on nearby nerves, resulting in nerve damage, pain, burning, tingling, and weakness of the affected muscle.

Diagnosis

Diagnosis of multiple myeloma involves examination of blood, urine, bone marrow, and bones.

Blood tests will reveal a number of abnormalities, including anemia with abnormal red blood cells. Blood calcium will be high in about 33% of all patients. A very specialized test called electrophoresis can be used to show an increased amount of circulating antibodies. This same type of test can be performed on urine to demonstrate that an increased amount of circulating antibodies is also present in urine. The technique of electrophoresis is based on the fact that proteins (including antibodies) have electrical charges. When electricity is applied to the blood or urine, different types of antibodies (with different electrical charges) will move different distances. This allows a healthcare professional to determine the type and the quantity of the various antibodies present in blood or urine. In both blood and urine electrophoresis, an increase in certain antibodies will give a result called an M-spike, indicative of multiple myeloma.

Examination of the bone marrow will require a test called a bone marrow aspiration. An extremely thin long needle is placed into the hip, and a sample of bone marrow is withdrawn. In multiple myeloma, bone marrow will have a significantly increased percentage of plasma cells, usually well over 10%.

X rays will show bone breakdown, including osteoporosis and the punched-out appearance of osteolysis. Pathologic fractures may also be identified.

Treatment

Because the treatments for multiple myeloma can be very damaging, and because the disease often progresses slowly, many patients are not treated until measurements of antibodies in the blood reach a particularly high level. Chemotherapy agents used in multiple myeloma include melphalan, cyclophosphamide, chlorambucil, and prednisone. These may be given over four to seven days in four to six week intervals. Chemotherapy may be given for several years. The disease usually recurs within a year after treatment has stopped. Chemotherapy can be given again, but each time the disease relapses it is less responsive to treatment.

Bone pain is often treated with radiation directed at the problem area. High blood levels of calcium may respond to treatment with prednisone. High blood levels of uric acid may improve with allopurinol. When anemia causes symptoms, blood transfusions may be necessary. It is important that patients with multiple myeloma drink large amounts of fluid to balance the effects of hyperviscous blood. In the case of kidney failure, a special procedure called plasmapheresis is very helpful. In this procedure, blood is filtered through a machine that is capable of removing the large amount of protein present. Infections will require prompt treatment with antibiotics.

Alternative treatment

One general recommendation for alternative cancer treatment includes dietary supplementation with beta-carotene, vitamin B₆, vitamin C, vitamin E, selenium, and zinc as antioxidant protection. There are also many herbs, including ginseng and astragalus, that are useful in treating cancer. Other recommendations include reducing stress through techniques like biofeedback training, guided imagery, and meditation. These same techniques are useful for pain relief.

Prognosis

The prognosis for patients with multiple myeloma varies. About 15% of all patients die within three months of diagnosis. About 60% of all patients respond to treatment and go on to live for an average of two and a half to three years after diagnosis. About 23% of all patients die of other illnesses associated with advanced age (including stroke, heart attack, lung disease, and diabetes).

Key Terms

Anemia

Any condition where the oxygen-carrying capacity of the red blood cells is reduced; symptoms often include fatigue.

Electrophoresis

A procedure during which an electrical current is applied to a solution of blood or urine. Because proteins have an electrical charge, the electrical current causes the proteins to move. Specific proteins can be identified by virtue of the distance moved in response to the current.

Malignant

Refers to certain abnormal characteristics of a cell, including uncontrollable growth and duplication, and an ability to invade nearby tissue.

Osteolysis

Softening, absorption, and destruction of bone tissue.

Osteoporosis

A condition where bones lose their mineral content (especially calcium). The bones then become weak and porous.

Plasma cells

A type of white blood cell (infection-fighting cell) produced within the bone marrow. Plasma cells produce antibodies.

Platelets

Blood cells produced within the bone marrow; involved in the clotting process.

White blood cells

The infection-fighting cells of the body produced within the bone marrow.

Further Reading

For Your Information

Books

• Longo, Dan L. "Plasma Cell Disorders." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.
• Malpas, James S. Myeloma: Biology and Management. Oxford: Oxford University Press, 1998.

  Periodicals

• Bataille, Regis, and Jean-Luc Harousseau. "Multiple Myeloma." The New England Journal of Medicine 336,23(June 5, 1997): 960+.
• McCarthy, Michael. "Clinical Notes from American Society of Haematology." The Lancet 346(December 16, 1995): 1621.
• Singer, Charles R. J. "Multiple Myeloma and Related Conditions." The New England Journal of Medicine 336(June 5, 1997): 1657+.

  Organizations

• International Myeloma Foundation. 2120 Stanley Hills Dr., Los Angeles, CA 90046. (800) 452-CURE.

Gale Encyclopedia of Medicine. Gale Research, 1999.