Multiple myeloma - symptoms and treatment

What is Multiple Myeloma and Definition

A CANCER of the BONE MARROW in which PLASMA cells, also called myeloma cells or myelocytes, proliferate, accumulating as lesions (growths) to develop within the BONE marrow cavities of the bones. The lesions prevent normal functioning of the bone marrow. They also damage bone tissue and weaken the bone structure. Plasma cells derive from lymphocytes that migrate to the bone marrow. Their function is to produce immune antibodies, or immunoglobulins, that are essential for the body’s IMMUNE RESPONSE. They generally make up less than 5 percent of the cells in the bone marrow. In multiple myeloma plasma cells make up 10 percent or more of the bone marrow’s cells. The cancerous plasma cells of multiple myeloma overproduce certain immune antibodies called monoclonal proteins or M-proteins. M-proteins alter the ways in which immunoglobulins bind with B-cell lymphocytes in the blood, reducing their ability to fight INFECTION.

The M-proteins also activate specialized phagocytic cells in the bone, called osteoclasts, accelerating the deconstruction phase of bone remodeling (the process through which bone tissue continuously replenishes). Osteoclastic activity releases excessive calcium into the bloodstream, affecting numerous body systems, including cardiovascular function and renal (kidney) function. The KIDNEYS produce ERYTHROPOIETIN (EPO), the HORMONE that stimulates the bone marrow to produce erythrocytes (red blood cells). Damage to the kidneys such as occurs with multiple myeloma reduces EPO production, resulting in moderate to significant ANEMIA. M-proteins can bind with erythrocytes in the blood, further reducing their ability to transport oxygen. M-proteins can also bind with other substances in the blood including hormones and cells such as platelets. M-protein binding with platelets results in COAGULATION (clotting) abnormalities including excessive bleeding or thrombosis (clot formation within the blood vessels).

In the late 1990s researchers achieved a significant breakthrough in identifying the possible causes of multiple myeloma with the discovery of a connection between multiple myeloma and certain infections, notably herpesvirus type 8 (which causes another cancer, KAPOSI’S SARCOMA) and HEPATITIS C. As well, doctors have long noted connections between multiple myeloma and occupational exposure to pesticides (notably DDT) and petroleum products, and to radiation exposure such as RADIATION THERAPY. Multiple myeloma is more common in people over age 55 and accounts for 1 percent of all cancers doctors diagnose in the United States each year. It is more common in men than women and affects twice as many African Americans, though researchers are unsure of the reasons.

Symptoms of Multiple myeloma and Diagnostic Path

About half of people diagnosed with multiple myeloma have no symptoms at the time of diagnosis, when blood tests performed for other reasons reveal the abnormalities consistent with multiple myeloma. Blood tests early in the course of the cancer may produce inconsistent and nonspecific findings that become relevant with subsequent diagnostic procedures. When symptoms are present they may include

• fatigue, especially with exertion
• frequent nosebleeds (EPISTAXIS) or easy bruising
• GASTROINTESTINAL BLEEDING
• PAIN, often in the back or that feels as though it originates in the bones
• excessive thirst
• HEADACHE
• a haze over the field of vision

Diagnostic blood tests typically show elevated blood calcium levels, altered blood cell counts, increased blood proteins, increased blood volume, the presence of M-proteins, and the presence of myelocytes (PLASMA cells) in the blood circulation. NEUTROPENIA and anemia are often present. Diagnostic imaging such as X-rays, COMPUTED TOMOGRAPHY (CT) SCAN, POSITRON EMISSION TOMOGRAPHY (PET) SCAN, and MAGNETIC RESONANCE IMAGING (MRI) allow the oncologist to assess the extent of bone involvement and damage. Bone marrow biopsy reveals high plasma cell counts and abnormal bone marrow structure.

Multiple myeloma Treatment Options and Outlook

CHEMOTHERAPY is the treatment of choice for multiple myeloma. The first chemotherapy agent developed to treat multiple myeloma in 1958, melphalan, remains the first line DRUG of choice today, commonly given in combination with prednisone, a corticosteroid medication. Oncologists use other chemotherapy agents, usually in combinations with each other and with CORTICOSTEROID MEDICATIONS, to tailor treatment regimens to an individual’s age and the cancer’s presentation, other health considerations, and preferences. Initial treatment typically produces REMISSION, though RECURRENCE within two years is common. Some people benefit from radiation therapy that targets myeloma lesions within the bones. New treatments continue to emerge as researchers gain understanding of the mechanisms of multiple myeloma.

Thalidomide and thalidomide analogs

Thalidomide, which debuted in the 1950s as a treatment for MORNING SICKNESS and insomnia in PREGNANCY and quickly gained notoriety for causing BIRTH DEFECTS, emerged in the late 1990s as a successful treatment in some people for multiple myeloma that resists other therapies. Thalidomide suppresses the maturation of lymphocytes to plasma cells. Thalidomide analogs (such as Revimid and Actimid) are drugs closely related in chemical structure to thalidomide. Oncologists may administer thalidomide in combination with prednisone or dexamethasone, corticosteroid medications that help suppress bone marrow activity to slow the production of cancerous plasma cells.

Proteasome inhibitors

In 2003 the US Food and Drug Administration (FDA) approved the proteasome inhibitor bortezomib (Velcade) for people who have experienced two relapses following conventional treatment approaches. Proteasome inhibitors block the actions of enzymes within cells that are crucial to the cell’s ability to divide (reproduce). Clinical studies continue to investigate the effectiveness of these drugs, which appear to cause fewer side effects than conventional chemotherapy, as first-choice treatment.

Bone marrow and stem cell transplantation

Autologous BONE MARROW TRANSPLANTATION or STEM CELL transplantation (self-transplantation with harvested cells), achieves remission in many people. For autologous transplantation, the oncologist harvests peripheral BLOOD STEM CELLS (PBSC) or stem cells from healthy areas of bone marrow; administers high-DOSE chemotherapy after cell harvesting to kill the cancerous bone marrow; and administers the harvested bone marrow or stem cells, which then grow to replace the cancerous bone marrow. Allogeneic stem cell transplantation, which uses stem cells from a tissue-matched donor, carries relatively high risks of complications including transplant rejection, infection, and other reactions, but is so far the only hope for a cure of multiple myeloma. Nonmyeloablative (the patient’s bone marrow is not destroyed) allogeneic stem cell transplantation reduces the high risks of high-dose chemotherapy. Though not curative it may offer increased survival time.

Adjunctive therapies

Oncologists use various medications to mediate the side effects of treatment as well as the complications that arise as the course of the cancer progresses. Among them are:

• Statins (such as Lipitor and Mevacor) counters the osteoclastic (bone destruction) stimulation M-proteins generate. Researchers discovered in the early 2000s that the statin medications used to treat HYPERLIPIDEMIA (elevated blood cholesterol and blood lipid levels) additionally stimulate osteoblastic (bone construction) activity, resulting in increased production of new bone tissue.
• Therapeutic EPO supplementation (Procrit) stimulates bone marrow production of erythrocytes, relieving anemia.
• Bisphosphonates bind to damaged bone cells and so prevent further osteoclastic action (destruction). This allows the body’s natural bone remodeling mechanisms to repair the damage and rebuild the bone. However, bisphosphonates present the potential for serious kidney damage.
• ANTIBIOTIC MEDICATIONS aggressively treat the infections that become increasingly common as dysfunction of the IMMUNE SYSTEM progresses.

Lifestyle factors

Because multiple myeloma affects bone remodeling, daily weight-bearing exercise such as walking is important to stimulate the body’s normal osteoblastic (bone-constructing) mechanisms. These mechanisms further help bone tissue retain calcium, reducing the amounts of calcium that leaches into the circulation. Drinking lots of water to maintain high HYDRATION is also especially important. Staying well hydrated helps offset the tendency of the blood to become hyperviscous (thickened) as a consequence of the changes in its constitution that take place with the multiple myeloma. It also helps protect the kidneys by lowering the concentration of calcium and M-proteins that they must filter from the blood and pass in the URINE. Nutritious EATING HABITS provide the body with the NUTRIENTS it needs to maintain the best health status possible.

Risk Factors and Preventive Measures

Though environmental exposure, notably to pesticides and radiation, appears to play a role in the development of multiple myeloma, researchers do not know the mechanisms of such exposure. Many people who develop multiple myeloma do not have a known history of exposure to substances so far linked with an increased risk for this form of cancer, making it difficult for health experts to recommend effective preventive measures.

Potential complications of both the multiple myeloma and its treatments present risks that affect the course of the cancer as well as the prognosis (outlook). M-proteins bind with numerous cell types, causing deposits to accumulate. Such deposits on NERVE cells tend to cause NEUROPATHY (pain or insensitivity). Such deposits within organs, such as the LIVER and the kidneys, may adversely affect their functions. Kidney damage may result in kidney failure and the need for dialysis. As well, chemotherapy agents and high-dose corticosteroids, standards of treatment for multiple myeloma, present the potential for numerous adverse effects. Most people who have multiple myeloma experience several periods of remission ranging from six months to two years in duration with each course of treatment.

See also AMYLOIDOSIS; CANCER TREATMENT OPTIONS AND DECISIONS; IMMUNOGLOBULIN; LEUKEMIA; LYMPHOMA.

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