Multiple myeloma is a type of cancer that affects the bone marrow (the spongy tissue found inside bone). Multiple myeloma is part of a spectrum of diseases called plasma cell dyscrasia. Plasma cells are a type of white blood cells responsible for forming antibodies (defense "weapons") against bacteria and foreign substances. In multiple myeloma, plasma cells lose their ability to respond to controlling signals from a hierarchy of immune cells, for reasons that are unclear.
When the myeloma cells become independent of the immune system, they divide into numerous cells that the body does not need and form large amounts of abnormal proteins that damage the bone, bone marrow, or other organs of the body. In the meantime, the body tries to rid itself of the excess abnormal protein through the kidneys. In some cases, the abnormal protein deposits in different organs, resulting in secondary amyloidosis.
As the myeloma cells continue to divide out of control, the space within the bone marrow narrows, impairing the production and function of red blood cells, white blood cells, and platelets. When these normal antibodies are impaired, the body loses resistance to infection, and the person may develop other diseases such as pneumonia or kidney infections. The myeloma cells physically displace the bone structure, as well as secrete a chemical that destroys the bone.
What causes multiple myeloma and plasma cell dyscrasia?
The exact cause of multiple myeloma and plasma cell dyscrasia is not clear. However, it appears that patients who have been involved in the agricultural, chemical, or radiology industries are at higher risk of developing the disease.
Who is affected by multiple myeloma?
The incidence of multiple myeloma is increasing at an alarming rate in the United States with approximately 15,000 new patients diagnosed each year. Although multiple myeloma is more common in older patients, it is affecting more younger patients as well. Multiple myeloma is most common among African-American men (with the highest incidence rate) while Caucasian women have the lowest incidence rate.
What are the signs and symptoms of multiple myeloma?
There are no specific signs or symptoms of multiple myeloma. The following symptoms, if unexplained and unresolved for 8 to 12 weeks, may prompt further testing for multiple myeloma.
- Decreased energy level, fatigue
- Flu-like symptoms
- Back pain (lower back pain is more common)
- Bone pain
- Bone fractures that occur without significant injury (called pathologic fractures)
- Unusual weight loss
- Abnormal bleeding such as bleeding gums or frequent nosebleeds
- Bruising easily (in rare cases, caused by low platelets or amyloid of the skin). Amyloids are abnormal protein-like deposits under the skin.
In advanced disease, symptoms may include:
- Confusion
- Nausea and vomiting
- Weakness
The symptoms of advanced disease may result from the high levels of calcium in the blood (hypercalcemia) or kidney failure.
How is multiple myeloma diagnosed?
The diagnosis of multiple myeloma is often delayed because the signs and symptoms may be similar to other illnesses, such as rheumatoid arthritis.
In multiple myeloma, the physical examination is generally normal. The kidneys and other organs are evaluated during the examination to detect any problems.
Multiple myeloma should be suspected in the presence of any combination of the signs and symptoms listed previously or when there is:
- Anemia (reduced hemoglobin, a protein in red blood cells)
- Unexplained protein in the blood or urine
- Unexplained calcium in the blood or urine
- Unexplained kidney failure (excess protein produced by abnormal myeloma cells can directly damage the kidneys)
- "Sausaging" (the appearance of sausage links) of the blood vessels of the eyes
- Presence of a plasmacytoma (a collection of plasma cells under the skin that form a mass) felt during the physical examination
- Tenderness or pain that radiates around the chest or waist in a belt-like fashion (detected by gentle pressure applied on the spine). This is caused by plasmacytomas of the spine that affect the spinal cord.
- Feeling of tenderness when light pressure is applied over affected bones or hips
What tests are performed to confirm the multiple myeloma diagnosis?
Blood tests, X-rays showing areas of bone damage, bone marrow biopsies, and the evaluation of kidney function can confirm the diagnosis of multiple myeloma. Many tests will be performed at the initial visit in order to make a correct diagnosis.
Blood and urine tests
The most common abnormality of multiple myeloma is an elevated protein level in the blood and urine. In 25 percent of patients, the calcium level may also be elevated.
Blood tests evaluating the levels of normal antibodies can also reveal the presence of multiple myeloma. There may be low levels of red blood cells, white blood cells, and platelets, depending on how much the bone marrow has been affected.
The levels of vitamin B12 or folate are low in about 10 percent of multiple myeloma patients.
Increased levels of uric acid and BUN/creatinine should also be evaluated, as well as an abnormal thickening of the blood. A 24-hour urine test will evaluate how much protein is passed through the kidneys over the course of one full day.
X-rays
Complete X-rays of the arms, legs, back, pelvis, and skull can detect the presence of bone damage so it can be treated promptly. Bone densitometry (bone density) may be performed to determine the strength of your bones. People with weaker bones may be at greater risk for bone damage due to multiple myeloma.
Biopsy
A bone marrow biopsy or aspiration, which can evaluate the number of myeloma cells and their activity in the bone marrow, may be performed to evaluate the extent of damage caused to the normal bone structure. The most common biopsy sites include the pelvis and the long bones of the arms and legs, where bone marrow is most concentrated.
What are the forms of multiple myeloma?
There are different forms of multiple myeloma, distinguished by the level of elevated protein in the blood and/or urine.
The forms of multiple myeloma include:
Monoclonal Gammopathy of Unknown Significance (MGUS)
This is the least aggressive subclass of plasma cell dyscrasia. Two percent of the American population 65 years or older have MGUS. Patients with MGUS usually have:
- Only a small abnormal protein elevation (less than 3.0 gm/dl and less than 2.0 gm/dl for IgG and IgA and IgM, respectively)
- Minimal or no bone marrow involvement. Normally, plasma cells make up a very small portion of the bone marrow -- less than 5 percent. People with MGUS have less than a 10 percent plasma cell presence in the bone marrow.
- No bone involvement
- Normal blood counts
- Usually normal levels of unaffected antibodies
The urine is usually free of monoclonal protein, however, it is not unusual to find small amounts of monoclonal light chains in the urine of MGUS patients. Patients with MGUS often have no symptoms, but they have a 20 to 25 percent chance of developing multiple myeloma or a related lymphoproliferative disorder. The remainder live a normal life.
Smoldering Multiple Myeloma (SMM)
Patients with SMM have the same characteristics as MGUS, except that:
- The serum monoclonal protein level is greater than 3.0 gm/dl
- The percentage of plasma cells in the bone marrow is higher (10 to 20 percent)
- More patients with SMM have the levels of their normal antibodies suppressed.
Patients with SMM do not have anemia, renal failure, or bone disease. Many patients with SMM do not have fatigue, pain, or other symptoms, but about half of patients with SMM will progress to multiple myeloma and follow its course. The other 50 percent will follow the course of MGUS.
Multiple Myeloma (MM)
Patients with multiple myeloma have:
- A monoclonal protein level greater than 3.0 gm/dl or greater than 2.0 gm/dl for IgG, IgA, and IgM, respectively
- Greater than 20 percent plasma cell presence in the bone marrow
- Normal immunoglobulins are low
Some people with myeloma may not feel tired or have pain, but they may show some signs of the disease. Depending on the stage of the disease, the timing of treatment is decided.
Plasmacytoma
Plasmacytoma is a collection of malignant "cancerous" plasma cells that form a mass. Plasmacytomas affect either bones or soft tissues where, depending on the site affected, the clinical cause is defined.
Plasmacytoma could be a free-standing disease or part of multiple myeloma, if the characteristics listed above are present.
A single plasmacytoma of the soft tissue or the bone could be cured by local treatment (such as radiation therapy). Multiple plasmacytomas or plasmacytomas that are part of multiple myeloma are treated with systemic therapy.
How is multiple myeloma treated?
There is no known cure for multiple myeloma. However, there are treatments that can slow the progression of multiple myeloma and reduce its harmful effects.
Because each type of multiple myeloma is different, treatment is tailored to each individual. The treatment will depend on several factors, including the type of multiple myeloma; the organs that are affected; the severity of symptoms; and the person's age, overall health, and medical history.
The treatment of multiple myeloma could be divided into three phases, with supportive therapy overlapping in all three:
Induction phase: The treatment is focused on reducing the amount of the disease and the severity of symptoms. Treatment is also aimed at slowing the progression of the disease. Chemotherapy and possibly radiation therapy may be used in this phase.
Maintenance phase: There is no current standard and no therapy is considered to be the accepted approach. However, steroids, biologic therapy, immune therapy, or bone marrow transplantation are potential treatments. These and other drugs that help to stop growth of blood vessels may also be used and are under investigation
Salvage therapy: This type of therapy is reserved for treating patients whose disease has not responded to other known effective therapies.
Supportive therapy: The use of growth factors, bone building drugs such as zoledronic acid (Zometa) or pamidronate (Aredia), immunoglobulins and antibiotics play a crucial role in the management of the disease.
Treatment decisions are critical in determining the survival and quality of life of patients with multiple myeloma. To be able to decide with your doctor what treatment is best, it is important for you to be well-informed. You should ask many questions and:
- Get a complete description of the treatment program.
- Find out how well the treatment has worked for others in similar situations.
- Find out about side effects.
- Ask about the pros and cons of alternatives versus no treatment at all.
What is the outlook?
Multiple myeloma is chronic and usually progresses over a number of years. Multiple myeloma can be potentially life-threatening when the kidneys and heart are affected.
Early diagnosis is the key to managing the disease before it becomes fatal. The outlook for people with multiple myeloma has improved due to earlier diagnosis, improved supportive care, and advances in medical management of the disease. Active research and new treatment methods are under investigation to control the disease.
Resources
The Cleveland Clinic Multiple Myeloma Program Support/Education Group is the largest hospital-based group in the United States. The group is unique in focusing on patient education and lecturing. Physicians, nurses, and other health care professionals present these lectures once a month. For more information, please call 216.445.1232 or email: husseim@ccf.org or saluanm@cc.ccf.org Visit our web site at clevelandclinic.org
The International Myeloma Foundation maintains a hotline for patients and others who need information about myeloma, its treatment, and management. The hotline number is: 800.452.CURE or 213.654.3023. To contact the IMF, write to:
International Myeloma Foundation
2120 Stanley Hills Dr.
Los Angeles, CA 90046
Phone: 213.654.3023
Fax: 213.656.1182
Multiple Myeloma Research Foundation provides current information on multiple myeloma and research. They can be reached at 203.972.1250 or write to:
The Multiple Myeloma Research Foundation
51 Locust Avenue, Suite 201
New Canaan, CT 06840
© Copyright 1995-2009 The Cleveland Clinic Foundation. All rights reserved.
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This information is provided by the Cleveland Clinic and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. This document was last reviewed on: 7/29/2005...#4413
