Multiple Myeloma Definition Multiple myeloma is a cancer of your plasma cells.

Plasma cells are a type of white blood cell present in your bone marrow.In multiple myeloma, a group of abnormal plasma cells (myeloma cells) multiplies,raising the number of plasma cells to a more than normal level. The result can beerosion of your bones. The disease also interferes with the function of your bonemarrow and immune system, which can lead to anemia and infection. Multiplemyeloma may also cause kidney problems.The disease is called multiple myeloma because myeloma cells can occur in multiple bone marrow sites in your body.If you have multiple myeloma but don't have symptoms, your doctors may justmonitor your condition. If you're experiencing symptoms, various treatments areavailable. Symptoms Although multiple myeloma may not cause symptoms early in the disease, it's likelythat you'll experience signs and symptoms as the disease progresses.Signs and symptoms of the disease can vary from person to person. Common multiplemyeloma symptoms include:

Bone pain. Presence of abnormal proteins which can be produced by myeloma cells in your blood or urine. These proteins which are antibodies or parts of antibodies are called monoclonal, or M, proteins. Often discovered during aroutine exam, monoclonal proteins may indicate multiple myeloma, but alsocan indicate other conditions.

High level of calcium in your blood. This can occur when calcium fromaffected bones dissolves into your blood.If you have a high calcium level in your blood, you may experience signs andsymptoms such as:

Excessive thirst and urination

Constipation

Nausea

Loss of appetite

Mental confusion

Anemia can occur as myeloma cells replace oxygen-carrying red blood cells in your bone marrow, which may lead to another common symptom fatigue.Other signs and symptoms of multiple myeloma may include:

Bone pain, particularly in your back or ribs

Unexplained bone fractures Repeated infections such as pneumonia, bladder or kidney infection, or sinusitis

Weight loss

Weakness or numbness in your legs Causes Although the exact cause isn't known, doctors do know that multiple myeloma beginswith one abnormal plasma cell in your bone marrow the soft, blood-producingtissue that fills in the center of most of your bones. This abnormal cell then starts tomultiply.Because abnormal cells don't mature and then die as normal cells do, they accumulate,eventually overwhelming the production of healthy cells. Healthy bone marrowconsists of a small number of plasma cells, less than 5 percent. But in people withmultiple myeloma, the number of plasma cells often increases to more than 10 percent.Because myeloma cells may circulate in low numbers in your blood, they can populate other bone marrow sites in your body, even far from where they began.Uncontrolled plasma cell growth can damage bones and surrounding tissue. It canalso interfere with your immune system's ability to fight infections by inhibiting your body's production of normal antibodies. Researchers investigating cause Experts aren't sure why this process begins. But, researchers are studying the DNA of plasma cells to try to understand what changes occur that cause these cells to becomecancer cells. Though they haven't yet discovered the cause of these changes, they havefound some common abnormalities in myeloma cells. For example, many myeloma

cells are missing all or part of one chromosome chromosome 13. Cells with amissing or defective chromosome 13 tend to be more aggressive and harder to treatthan are cells with a normal chromosome 13. A connection with MGUS Multiple myeloma sometimes develops from a condition called monoclonalgammopathy of undetermined significance (MGUS). MGUS is more common inadults over age 50. This condition, like multiple myeloma, is marked by the presenceof M proteins produced by abnormal plasma cells in your blood. However, inMGUS, the amount of the abnormal proteins isn't high enough to cause harm, and nodamage to the bones occurs. Risk factors Multiple myeloma isn't contagious. Most people who develop multiple myeloma haveno clearly identifiable risk factors for the disease.Some factors that may increase your risk of multiple myeloma include:

Age. The majority of people who develop multiple myeloma are older than 50,with most diagnosed around age 70. Few cases occur in people younger than40.

Sex. Men are more likely to develop the disease than are women.

Race. Blacks are about twice as likely to develop multiple myeloma as arewhites.

History of a monoclonal gammopathy of undetermined significance. Everyyear 1 percent of the people with MGUS in the United States develop multiplemyeloma.

Obesity. Your risk of multiple myeloma is increased if you're overweight or obese.Other factors that may increase your risk of developing multiple myeloma includeexposure to radiation and working in petroleum-related industries. When to seek medical advice If you're persistently more tired than you used to be, you've lost weight, and youexperience bone pain, repeated infections, loss of appetite, excessive thirst andurination, persistent nausea, increased constipation, or weakness or numbness in your legs, your signs and symptoms may indicate multiple myeloma or other seriousdiseases. See your doctor to determine the underlying cause. Tests and diagnosis Your doctor may first detect signs of multiple myeloma before you ever havesymptoms through blood and urine tests conducted during a routine physical exam.If you don't yet have symptoms, these lab tests may be repeated every few months so that your doctor can track whether your disease is progressing and determine the besttime to start treatment. Blood and urine tests A blood test called serum protein electrophoresis separates your blood proteins andcan detect the presence of M proteins, called an "M spike," in your blood. Parts of M proteins may also be detected in a test of your urine when found in urine, they'rereferred to as Bence Jones proteins.If your doctor discovers M proteins, you'll likely need additional blood tests tomeasure blood cell counts and levels of calcium, uric acid and creatinine. Your doctor may also conduct other blood tests to check for beta2-microglobulin another protein produced by myeloma cells or to measure the percent of plasma cells inyour bone marrow. Other tests You may also need other tests. They may include:

Imaging. X-rays of your skeleton can show whether your bones have anythinned-out areas, common in multiple myeloma. If a closer view of your bones is necessary, your doctor may use magnetic resonance imaging (MRI)or computerized tomography (CT) scanning.

Bone marrow examination. Your doctor may also conduct a bone marrowexamination by using a needle to remove a small sample of bone marrowtissue. The sample is then examined under a microscope to check for myelomacells. Staging and classification These tests can help confirm whether you have multiple myeloma or another condition. If tests indicate you have multiple myeloma, the results from these testsallow your doctor to classify your disease as stage 1, stage 2 or stage 3. People withstage 3 myeloma are more likely to have one or more signs of advanced disease,including greater numbers of myeloma cells and kidney failure.

Complications Multiple myeloma can result in several complications:

Impaired immunity. Myeloma cells inhibit the production of antibodiesneeded for normal immunity. Having multiple myeloma may make you morelikely to develop infections, such as pneumonia, sinusitis, bladder or kidneyinfection, skin infections and shingles.

Bone problems. Multiple myeloma also can affect your bones, leading toerosion of bone mass and fractures. The condition may cause compression of your spinal cord. Signs of this medical emergency include weakness, or even paralysis, in your legs.

Impaired kidney function. Multiple myeloma may cause problems withkidney function, including kidney failure. Higher calcium levels in the bloodrelated to eroding bones can interfere with your kidneys' ability to filter your blood's waste. The proteins produced by the myeloma cells can cause similar problems, especially if you become dehydrated.

Anemia. As cancerous cells crowd out normal blood cells, multiple myelomacan also cause anemia and other blood problems. Treatments and drugs Generally, if you have multiple myeloma and aren't experiencing symptoms, you don'tneed treatment. However, your doctors will likely monitor your condition at variableintervals, checking for signs such as increasing levels of M protein in your bloodor urine that indicate the disease is progressing. If it is, you may need treatment tohelp prevent symptoms. In people diagnosed with asymptomatic multiple myeloma,the risk of developing symptoms is about 10 percent a year for the first five years after learning that they have the disease.If you're experiencing symptoms, treatment can help relieve pain, controlcomplications of the disease, stabilize your condition and slow the progress of thedisease. Standard treatments for myeloma Though there's no cure for multiple myeloma, with good treatment results you canusually return to near-normal activity. The appropriate multiple myeloma treatmentdepends on your needs, medical status and general health. You may also wish toconsider approved clinical trials as an option.Standard treatment options include:

Chemotherapy.

Chemotherapy involves using medicines taken orally as a pill or given through an intravenous (IV) injection to kill myeloma cells.Chemotherapy is often given in cycles over a period of months, followed by arest period. Often chemotherapy is discontinued during what is called a plateau phase or remission, during which your M protein level remains stable.You may need chemotherapy again if your M protein level begins to rise.Common chemotherapy drugs used to treat myeloma are melphalan (Alkeran),cyclophosphamide (Cytoxan), vincristine (Oncovin), doxorubicin(Adriamycin) and liposomal doxorubicin (Doxil).

Corticosteroids. Corticosteroids such as prednisone and dexamethasone(Decadron) have been used for decades to treat multiple myeloma. They aretypically given as pills. Some research suggests that high doses of steroidsmay not be needed, and that lower doses may be safer and more effective.

Stem cell transplantation. This treatment involves using high-dosechemotherapy usually high doses of melphalan along with transfusion of previously collected immature blood cells (stem cells) to replace diseased or damaged marrow. The stem cells can come from you or from a donor, andthey may be from either blood or bone marrow.

Thalidomide (Thalomid). Thalidomide, a drug originally used as a sedativeand to treat morning sickness in the 1950s, was removed from the market after it was found to cause severe birth defects. However, the drug receivedapproval from the Food and Drug Administration (FDA) again in 1998, first as a treatment for skin lesions caused by leprosy. Thalidomide is currently FDA-approved in conjunction with the corticosteroid called dexamethasone for thetreatment of newly diagnosed cases of multiple myeloma. This drug is givenorally.

Bortezomib (Velcade). Velcade was the first approved drug in a new class of medications called proteasome inhibitors. It is administered intravenously. Itworks by blocking the action of proteasomes, which causes cancer cells to die.One study showed that bortezomib had more than twice the response rate of acommonly used drug, dexamethasone. Bortezomib is approved by the FDA for use in a treatment for people with multiple myeloma who have received atleast one prior therapy.

Lenalidomide (Revlimid). Lenalidomide is chemically similar tothalidomide, but appears to be more potent and cause fewer side effects. It isgiven orally. Lenalidomide is FDA-approved for use in combination withdexamethasone as a treatment for people who have received at least one prior therapy for multiple myeloma.

Radiation therapy. This treatment uses high-energy penetrating waves todamage myeloma cells and stop their growth. Radiation therapy may be usedto target myeloma cells in a specific area for instance, to more quicklyshrink a tumor that's causing pain or destroying a bone. Initial therapy for myeloma The initial chemotherapy used to treat multiple myeloma depends on whether you'reconsidered a candidate for stem cell transplantation. Factors such as the risk of your disease progressing, your age and your general health play a part in determiningwhether stem cell transplantation may be right for you.

If you're considered a candidate for stem cell transplantation: Your initialtherapy will likely exclude melphalan because this drug can have a toxic effecton stem cells, making it impossible to collect enough of them. You may begintreatment with the most common initial myeloma therapy in the United States,thalidomide plus dexamethasone. Or your doctor may instead recommend anewer regimen, lenalidomide plus low-dose dexamethasone.Your stem cells will likely be collected after you've undergone three to four months of treatment with these initial agents. Your doctor may recommendundergoing the stem cell transplant soon after your cells are collected or delaying the transplant until after a relapse, if it occurs. Your age and your personal preference are important factors that will help your doctor make hisor her recommendation.

If you're not considered a candidate for stem cell transplantation: Your initial therapy is likely to be a combination of melphalan, prednisone andthalidomide (MPT). If the side effects are intolerable, melphalan plus prednisone is another option (MP). This type of therapy is typically given for about 12 to 18 months. Treatments for relapsed or treatment-resistant multiple myeloma Most people who are treated for multiple myeloma eventually experience a relapse of the disease. And in some cases, none of the currently available, first-line therapies slow the cancer cells from multiplying. If you experience a relapse of multiplemyeloma, your doctor may recommend repeating another course of the treatment thatinitially helped you. Another option is trying one or more of the other treatmentstypically used as first-line therapy, either alone or in combination.Research on a number of promising new treatment options is ongoing, and these drugsoffer important options for those with multiple myeloma. Talk to your doctor aboutwhat clinical trials may be available to you. Treating complications Because multiple myeloma can cause a number of complications, you may also needtreatment for those specific conditions. For example:

Back pain. Taking pain medication or wearing a back brace can help relievethe back pain you might experience with multiple myeloma.

Kidney complications. People with severe kidney damage may need dialysis.

Infections. Antibiotics may be necessary to help treat infections or to helpreduce your risk of them.

Bone loss. You may take medications called bisphosphonates, such as pamidronate (Aredia) or zoledronic acid (Zometa), which bind to the surfaceof your bones and help prevent bone loss. Treatment with these drugs isassociated with the risk of harm to the jawbone. If you're taking thesemedications, don't have dental procedures done without consulting your doctor first.

Anemia. If you have persistent anemia, your doctor may prescribeerythropoietin injections. Erythropoietin is a naturally occurring hormonemade in the kidneys that stimulates the production of red blood cells. Researchsuggests that the use of erythropoietin may increase the risk of blood clots insome people with myeloma. Lifestyle and home remedies The following tips may help you keep multiple myeloma under control:

Stay active. Exercise helps keep your bones stronger. If pain keeps you from being active, ask your doctor about ways to lessen the pain.

Drink fluids. Drinking fluids can help keep you from becoming dehydrated.And by drinking plenty of fluids, you help dilute the Bence Jones proteinfragments in your urine, which may help prevent kidney damage.

Eat a balanced diet. One way to promote your overall health and cope withany form of cancer is to eat well. The amount of M protein in your system isn'taffected by how much protein you eat, so there's no need to limit proteinintake unless told otherwise by your doctor. Don't take vitamins, herbs or medications without your doctor's approval because they may interfere withyour treatment. Coping and support A diagnosis of cancer can be extremely challenging. Remember that no matter whatyour concerns or prognosis, you're not alone. These strategies and resources maymake dealing with cancer easier:

Know what to expect. Find out everything you can about your cancer thetype, stage, risks, your treatment options and their side effects. The more youknow, the more active you can be in your care. In addition to talking with your doctor, look for information in your local library and on the Internet. The National Cancer Institute will answer questions over the phone from the publicat 800-4CANCER, or 800-422-6237. Or contact the American Cancer Society at 800-ACS-2345, or 800-227-2345. Information is also available ontheir Web sites.

Be proactive. Although you may feel tired and discouraged, don't let others including your family or your doctor make important decisions for you.It's vital that you take an active role in your treatment.

Maintain a strong support system. Having a support system and a positiveattitude can help you cope with any issues, pain and anxieties that mightoccur. Although friends and family can be your best allies, they sometimesmay have trouble dealing with your illness. If so, the concern andunderstanding of a formal support group or others coping with cancer can beespecially helpful. Although support groups aren't for everyone, they can be agood source for practical information for you and your family, too. You mayalso find you develop deep and lasting bonds with people who are goingthrough the same things you are.

Set reasonable goals. Having goals helps you feel in control and can give youa sense of purpose. But don't choose goals you can't possibly reach. You maynot be able to work a 40-hour week, for example, but you may be able to work at least part time. In fact, many people find that continuing to work can behelpful.

Take time for yourself. Eating well, relaxing and getting enough rest can helpcombat the stress and fatigue of cancer. Also, plan ahead for the downtimes,when you may need to rest more or limit what you do.

Stay active. Having cancer doesn't mean you have to stop doing the things you enjoy or normally do. For the most part, if you feel well enough to do something, go ahead and do it. It's important to stay involved as much as you can.