Multiple myeloma

INTRODUCTION — Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow. Normally, plasma cells produce antibodies and play a key role in immune function. However, uncontrolled growth of these cells leads to bone pain and fractures, anemia, infections, and other complications.

In the United States, about 4 out of 100,000 individuals are diagnosed with MM each year. This condition is slightly more common among men than women, and almost twice as common among blacks as among whites. The average age at diagnosis is 65 to 70 years.

The current treatment options for MM include watchful waiting (for early or smoldering multiple myeloma), chemotherapy, immune-modulating drugs, and stem cell transplantation. Multiple myeloma is seldom cured, but treatment can relieve symptoms, induce remission, and prolong life.

The cause of MM is unknown. Exposure to radiation, organic chemicals (such as benzene), herbicides, and insecticides may play a role. Genetic factors and viral infection may also influence the risk of developing multiple myeloma.

FEATURES — Multiple myeloma can produce a wide variety of symptoms.

Bone symptoms — Most individuals develop bone pain in the back or chest or, less commonly, the arms and legs, at the time of diagnosis. The pain is usually triggered by movement and is absent at night, except when changing positions.

MM causes both generalized bone loss throughout the body as well as bone erosions (lytic lesions on x-ray) in specific areas. The bone loss and erosions can lead to osteoporosis and fractures. Many individuals with multiple myeloma experience fractures of the vertebrae (the bones of the spine), which can lead to a loss of height; about 30 percent of individuals experience fractures in other bones, often with little or no preceding trauma. For this reason they are called "pathologic fractures."

High blood calcium levels — Because bones contain large amounts of calcium, the breakdown of bone in MM can lead to high blood calcium levels (called hypercalcemia). High blood calcium levels occur in 10 to 15 percent of individuals, and the symptoms may include loss of appetite, nausea, vomiting, frequent urination, increased thirst, constipation, weakness, confusion, stupor, or coma.

Anemia — About two thirds of individuals have anemia (low red cell count) at the time of diagnosis, and anemia eventually occurs in almost all individuals. The signs and symptoms of anemia include paleness, weakness, and fatigue.

Impaired kidney function — The excess proteins and high blood calcium levels associated with MM can damage the kidneys. Kidney function is abnormal at diagnosis in about half of individuals with multiple myeloma. Occasionally, kidney failure is the first symptom of MM.

Thickened blood — The excessive production of proteins by the malignant plasma cells in MM can cause a thickening of the blood (called hyperviscosity syndrome). The symptoms may include bleeding from the nose and mouth, blurred vision, neurologic symptoms, and congestive heart failure.

Neurologic symptoms — Fractures of the vertebrae can lead to increased pressure on the nerve roots where they exit the spine, causing neurologic symptoms (called radiculopathy). This complication of multiple myeloma most commonly affects the chest, lower back, or legs, and the symptoms may include odd sensations (numbness or tingling), pain, or muscle weakness.

Occasionally, neurologic symptoms occur because plasma cells grow within the spinal canal and press on the spinal cord. The symptoms may include severe back pain, muscle weakness, especially of the legs, numbness or tingling, and loss of control of bowel or bladder function (incontinence). Spinal cord compression is a medical emergency and requires immediate treatment to relieve the pressure and prevent permanent damage.

Generalized symptoms — The generalized symptoms of MM include an increased susceptibility to infections (especially during chemotherapy) and weight loss. Occasionally, it causes increased bleeding or tumors of the ribs. In individuals with advanced MM, tumor cells may accumulate beneath the skin, causing large purple-colored bumps.

DIAGNOSTIC TESTING — The diagnosis of MM is based upon the presence of characteristic signs and symptoms of the disease and on the results of tests of the blood and bone marrow. Several different tests are used to determine the presence and severity of MM. In some individuals with early MM or related conditions, it may be necessary to repeat these tests periodically until the diagnosis is certain.

After MM is confirmed, additional tests are used to check for the presence of impaired kidney function, anemia, thickening of the blood, and other complications of multiple myeloma.

Blood and urine tests for monoclonal protein — An abnormal protein produced by the plasma cells, called a monoclonal (M) protein (sometimes called a "paraprotein"), can be found in the blood or urine of almost all patients with MM, which helps establish the diagnosis. These proteins serve no useful function, and may be responsible for increases in the thickness of the blood, kidney damage, or bleeding problems.

However, it is important to remember that not everyone with a monoclonal protein has MM. The diagnosis requires, in addition to the monoclonal protein, one or more abnormalities such as anemia, bone lesions (see "X-rays" below), kidney failure, or high calcium levels in the blood (see "Criteria for diagnosis" below).

Bone marrow examination — In most individuals with MM, a bone marrow aspiration and biopsy (a collection of a small sample of bone marrow for laboratory analysis, usually taken from the hip) shows that plasma cells comprise an abnormally high percentage of bone marrow cells (more than 10 percent). It may be necessary to collect samples from different areas because MM may affect the marrow of some bones but not others.

X-rays — In about 80 percent of individuals, routine x-rays show distinct, round (lytic) areas of bone erosion; generalized thinning of the bones; and/or fractures at the time of diagnosis. The bones most commonly involved are the vertebrae, the ribs, the pelvic bones, and the bones of the thigh and upper arm.

Genetic and chromosomal tests — Specialized tests may reveal genetic or chromosomal abnormalities of the plasma cells in individuals with MM. In general, such abnormalities are associated with a poorer prognosis. The results of these tests are helpful for predicting the response to treatment and survival.

Plasma cell labeling index — The plasma cell labeling index determines how rapidly the abnormal plasma cells are growing and dividing. Patients in whom the labeling index is low tend to have slower disease progression than those with high values. This test is also useful for distinguishing MM from related conditions that generally have a better prognosis. A normal plasma cell labeling index suggests that MM is less likely, while an elevated index suggests that multiple myeloma is more likely. However, this test is not generally available.

Criteria for diagnosis — The diagnosis of multiple myeloma requires the following: A bone marrow aspirate or biopsy showing that at least 10 percent of the cells are plasma cells or the presence of a plasma cell tumor (called a plasmacytoma), plus: M protein in the blood or urine, or Evidence of damage to the body as a result of the plasma cell growth, such as destructive bone lesions, kidney failure, anemia, or high calcium in the blood.

STAGING AND PROGNOSIS — The simplest measure of prognosis in MM is based on blood levels of two markers: beta-2-microglobulin and albumin. In general, higher levels of beta-2-microglobulin and lower levels of albumin are associated with a poorer prognosis. This staging system is referred to as the International Staging System, or ISS.

The older Durie-Salmon staging system divided patients into three stages: Stages I, II, and III, corresponding to low, intermediate, and high cell mass, depending on such factors as the degree of anemia, calcium level, kidney function, presence or absence of bone lesions, and the amount of the abnormal protein. It is best used as a measure of the overall amounts of malignant plasma cells present in the patient, and is less useful as a measure of prognosis.

TREATMENT OVERVIEW — The treatment of MM is complex because of rapid advances in stem cell transplantation, medications, and better supportive care. The main options for therapy include: Chemotherapy Stem cell (bone marrow) transplantation

Each option needs to be weighed carefully. Because current therapy is rarely curative, patients will likely go through many treatment options during the course of their illness. Stem cell transplantation may not be an option for many patients because of advanced age, presence of other serious illness, or other physical limitations (see "Stem cell transplantation" below).

CHEMOTHERAPY — Chemotherapy is usually the first treatment recommended. In most individuals, chemotherapy partially controls MM; rarely, chemotherapy leads to complete remission. The response to initial chemotherapy also helps to estimate how long an individual will survive.

A person who "responds" to chemotherapy must have a 50 percent reduction in blood and urine levels of the abnormal M protein and an improvement of symptoms. Individuals who have any response to chemotherapy (even if it does not meet the above definition) survive approximately three years, while individuals who do not have a response survive approximately one to two years.

The treatment of MM is tailored to a variety of individual factors, including the stage of MM, age, overall health, and personal preferences.

Timing of chemotherapy — Multiple myeloma can remain stable for prolonged periods of time. Individuals with early myeloma (stage I: low cell mass by the Durie-Salmon staging system) who have no symptoms (often called smoldering or indolent myeloma) may be advised to wait months to years before considering chemotherapy.

Individuals with a related condition, called monoclonal gammopathy of undetermined significance (MGUS), do not require treatment, although long-term follow-up is needed; a percentage of patients with MGUS will eventually develop full-blown myeloma.

Chemotherapy is recommended for individuals who have symptoms of multiple myeloma at the time of diagnosis.

Initial chemotherapy options — The type of chemotherapy initially recommended for treatment of MM depends upon the patient's age, underlying medical illnesses, and the likelihood of undergoing stem cell transplantation in the future. Melphalan prednisone (MP) chemotherapy is usually recommended first for individuals over the age of 75 and younger individuals who will not be undergoing stem cell (bone marrow) transplantation at a later time because of associated illnesses or poor health. If later transplantation is a possibility, stem cells should be collected before the start of melphalan chemotherapy because this drug can cause long-lasting damage to stem cells. For individuals between 65 and 75 years who do not plan to undergo stem cell transplantation, melphalan, prednisone, and thalidomide (MPT) is recommended. This is also recommended if a rapid response is needed.

For either of the above groups, chemotherapy is usually continued until the patient reaches a plateau phase (see "Plateau phase" below). For individuals who hope to undergo stem cell transplantation, treatment with dexamethasone plus thalidomide is recommended (thal/dex) or another similar regimen is recommended. These treatments do not interfere with later collection of stem cells. For individuals who have renal failure at the time initial chemotherapy is needed, treatment with dexamethasone alone or dexamethasone plus thalidomide is often preferred.

Melphalan prednisone (MP) chemotherapy — Melphalan (Alkeran, a drug in the alkylating agent class of chemotherapy drugs) and prednisone (a steroid) are taken by mouth three times daily for seven days; this is repeated every four to six weeks. A one week dose is called a cycle. It may take 6 to 12 months or even longer for blood tests to reflect the full effects of this chemotherapy on multiple myeloma.

Between 50 and 60 percent of individuals with MM have a response to melphalan-prednisone chemotherapy. The average survival among individuals treated with this chemotherapy is three years.

During melphalan-prednisone chemotherapy, periodic blood tests are needed to ensure that an individual has adequate levels of white blood cells (cells that fight infection) and platelets (blood components that are important for clotting). The dose of melphalan must be adjusted based on these findings.

Thalidomide — Thalidomide (Thalomid®) is an immune-modulating drug that is effective in the treatment of relapsed MM, either alone or in combination with steroids such as dexamethasone or chemotherapy. Thalidomide is not yet approved for the initial treatment of myeloma, but is commonly used "off label" for this purpose.

Among individuals treated with thalidomide alone for relapsed myeloma, 58 percent survive at least one year, and, on average, 48 percent survive at least two years. The possible side effects of thalidomide, when used for prolonged periods of time, include nerve damage, usually involving the sensory and motor functions of nerves serving the arms and legs, which may not be reversible.

Thalidomide is taken orally. The main side effects are sleepiness, constipation, skin rash, and nerve damage. The use of this medicine in combination with dexamethasone or chemotherapy increases the chance of developing blood clots, and may require the use of anticoagulants ("blood thinners") to prevent this from happening. Thalidomide causes severe birth defects and it is absolutely unsafe (contraindicated) for pregnant women.

Lenalidomide (Revlimid®) is a closely related drug (analogue) of thalidomide. It is currently available as a second line treatment, and is being evaluated as a first line treatment in clinical research trials. It has shown clinical activity in MM with fewer side effects than thalidomide (see "Clinical trials" below).

Bortezomib — Bortezomib (Velcade™) is a proteasome inhibitor that is effective in treating patients with refractory MM and other tumors. It is currently available as a second line treatment, and is being evaluated as a first line treatment in clinical research trials. It is given intravenously, and its main side effects are low blood counts and nerve damage.

Chemotherapy-related infections — There is an increased risk of infection during the first two months of chemotherapy. Infections often require stopping chemotherapy. Therefore, daily antibiotics may be recommended for individuals starting chemotherapy to reduce the risk of infection and the severity of infections that do occur.

Plateau phase — Chemotherapy is usually continued until MM enters a stable (plateau) phase. The plateau phase is reached when the myeloma becomes stable and shows no signs of progressing. Although this phase is usually temporary, it typically lasts six months or longer. The plateau phase occurs in about one half of individuals after chemotherapy.

Achieving this phase usually requires at least six cycles of chemotherapy, but it may require additional cycles. Additional chemotherapy is not needed or recommended during the plateau phase.

STEM CELL TRANSPLANTATION — Stem cell or bone marrow transplantation is a treatment option for some individuals with MM. There are three types of transplantation, based on the source of the stem cells: Autologous transplantation: the stem cells are obtained from the individual with MM. This is the type of transplantation that is most commonly recommended. Allogeneic transplantation: the stem cells or bone marrow are obtained from a donor with a tissue type matching that of the patient. This type of transplantation carries very high risks and is not recommended for most individuals with MM. Syngeneic transplantation: the stem cells or bone marrow are obtained from an identical twin of the individual. This is the optimal form of transplant at this time, but only rare individuals with MM have an available identical twin who can serve as a donor.

Transplantation, when successful, prolongs survival, leads to a remission, and, infrequently, cures MM. However, transplantation has several limitations. The high-dose chemotherapy (even with radiation) given before transplantation usually fails to kill all of plasma cells, allowing the condition to relapse. Such treatment also puts the patient at risk for serious infections and bleeding, which might be fatal. (See "Patient information: Overview of bone marrow transplantation").

Autologous stem cell transplantation — Autologous stem cell transplantation refers to transplantation with an individual's own stem cells. During this procedure, stem cells are collected and frozen for later use. High-dose chemotherapy is then given to kill as many plasma cells as possible, and the stem cells are thawed and returned to the patient. Stem cells obtained from the peripheral blood of the patient are preferred over bone marrow, because peripheral blood stem cells take up residence in tissues more quickly and are less likely to be contaminated with residual malignant plasma cells.

At present, autologous stem cell (or bone marrow) transplantation is appropriate for up to 50 percent of individuals with multiple myeloma.

Procedure — After initial therapy with a regimen such as thalidomide/dexamethasone for about four months, an individual is given granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate the production of stem cells. Stem cells are then collected from the blood, frozen, and stored for later use.

After an individual recovers from the stem cell collection, he or she is given high-dose chemotherapy with melphalan (or similar drugs) to kill as many of the malignant plasma cells as possible; then the previously collected stem cells are thawed and returned to the patient. In about one-half of patients, this procedure can be done on an outpatient basis.

Alternatively, after stem cell collection, an individual may be given standard chemotherapy with melphalan (or similar drugs) to achieve a plateau phase. At the time of relapse, high doses of melphalan (or similar drugs) are given, and the previously collected stem cells are returned to the patient ("delayed transplantation").

Role of age and stage of myeloma — Because autologous transplantation has serious side effects, it is generally not recommended for individuals over the age of 70. However, this procedure may be an option for some individuals over the age of 70 who are otherwise healthy. The likelihood of a good response to transplantation is somewhat lower for older adults than for younger adults, but the effects of age on survival after transplantation are still uncertain.

Autologous stem cell transplantation is not recommended for individuals with early stage (Durie-Salmon stage I) or smoldering myeloma.

Importance of prior treatment — Autologous transplantation is not recommended for individuals who have received prolonged chemotherapy with alkylating drugs (such as melphalan). In such instances, it is very difficult to collect a sufficient number of healthy stem cells for transplantation.

If transplantation is a possibility, initial therapy with dexamethasone alone or thalidomide plus dexamethasone is usually recommended. In contrast to alkylating drugs such as melphalan, these agents do not cause damage to the stem cells.

Effectiveness — About one to two percent of individuals die from complications related to transplantation. However, compared with chemotherapy, autologous stem cell transplantation is more likely to produce a response, and is associated with survival approximately 12 months longer than that produced by chemotherapy alone.

Single versus double autologous transplantation — Double autologous transplantation (two consecutive autologous transplantations) may be more effective than single autologous transplantation if the first transplant has not produced a complete or near complete response. The second transplantation is usually performed within six months of the first.

Among individuals undergoing double transplantation, 51 percent have a complete response, lasting, on average, 50 months. One study has shown that double transplantation improves long-term survival relative to single transplantation with the greatest benefit seen in patients who have not achieved an excellent response with the first transplant.

Allogeneic bone marrow transplantation — An allogeneic stem cell or bone marrow transplantation is a treatment option for only 5 to 10 percent of individuals with multiple myeloma. This type of transplantation has two advantages over autologous transplantation: the donated stem cells do not contain any malignant plasma cells, and the transplanted cells may target and help control any remaining myeloma cells. This latter beneficial effect is called the "graft versus tumor" effect. However, allogeneic transplantation is also associated with a "graft versus host" effect, in which cells from the donor attack tissues of the host, resulting in damage to various organs, such as the skin, liver, and intestines.

Allogeneic transplantation requires bone marrow or stem cells from a donor with a matching tissue type. Under the best conditions, a sibling may qualify as a donor; otherwise national bone marrow donor banks may be employed to find a donor with a matching tissue type. The donated bone marrow or stem cells are given to the patient after he/she receives appropriate doses of high-dose chemotherapy and radiation to reduce the number of malignant plasma cells.

About one half of individuals have a complete response after allogeneic transplantation. Thirty percent of individuals live for at least four years, and 20 percent of individuals live for at least 10 years. The likelihood of a complete response to allogeneic bone marrow transplantation is highest in individuals with a lower number of myeloma cells and in individuals who have had a complete response to the initial chemotherapy.

Although multiple myeloma usually relapses after allogeneic transplantation, some individuals are cured of multiple myeloma after this type of transplantation.

Unfortunately, approximately 25 percent of individuals who undergo allogeneic transplantation die from transplant-related complications, such as infection, lung inflammation, and graft-versus-host disease. Thus, the potential benefit of allogeneic transplantation (long-term disease control or cure) must be weighed against the potential for immediate morbidity and mortality. Primarily because of this toxicity, allogeneic transplantation is seldom used for the treatment of myeloma.

Nonmyeloablative allogeneic transplantation — Because autologous transplantation is not often curative and allogeneic transplantation carries a high mortality, other solutions have been sought. These include nonmyeloablative allogeneic transplants (often called "mini transplants") in which the patient receives a lower dose of chemotherapy prior to an allogeneic transplant.

The best results have been seen when a nonmyeloablative allogeneic transplantation is conducted following an initial autologous transplantation. However, the best preparative regimen and the control of graft versus host disease are evolving. We believe that this procedure should be done only in a research setting.

Donor lymphocyte infusion — Donor lymphocyte infusion is an experimental procedure that is a good option for individuals who have a relapse of multiple myeloma after allogeneic stem cell transplantation. During this procedure, lymphocytes collected from the original donor are given to the individual; these lymphocytes target the myeloma cells and may produce a beneficial "graft versus tumor" effect. Fifty-two percent of individuals have a response to this procedure, and 22 percent of individuals have a complete response.

Syngeneic transplantation — A syngeneic transplantation refers to a transplantation between identical twins. For individuals who have an identical twin, this treatment option is more effective than either autologous or allogeneic transplantation.

Remission after transplantation — The strict definition of remission requires that there are no signs or symptoms of multiple myeloma and that highly sensitive tests do not detect any abnormal plasma cells. This type of remission occurs in about 4 percent of individuals after autologous transplantation and about 19 percent of individuals after allogeneic transplantation.

TREATMENT OF COMPLICATIONS — Multiple myeloma can cause a variety of complications, some of which are life-threatening. It is important to treat these complications in addition to treating MM itself.

High blood calcium levels — High blood calcium levels develop as bone is lost. Individuals with MM should remain as active as possible because physical activity helps counter bone loss.

The treatment of high blood calcium levels usually includes use of intravenous fluids and prednisone. If this treatment is not effective, treatment with drugs that counter bone loss, such as zoledronic acid (Zometa™) or pamidronate (Aredia™), a class of drugs called bisphosphonates, may be recommended.

Impaired kidney function — Kidney function becomes impaired in about one half of individuals with multiple myeloma. The treatment of impaired kidney function is aimed at the specific underlying cause.

Treatment usually includes intravenous fluids; it may also include dialysis (a type of blood filtration used for kidney failure), prednisone (a steroid that can indirectly lower blood calcium levels), and allopurinol, a drug that can lower blood levels of uric acid, a waste product from the increased turnover of the malignant plasma cells, which can damage the kidneys.

Patients are advised to stay well-hydrated and should drink enough fluid to produce three liters of urine daily if they have Bence Jones proteinuria (increased light chains in the urine). They should also avoid using any nonsteroidal anti-inflammatory drugs (NSAIDs, such as Advil®, Motrin®, Aleve®) because these drugs might worsen kidney function.

If impaired kidney function has progressed to kidney failure, the treatment options include hemodialysis or peritoneal dialysis. Advanced degrees of kidney failure are usually not reversible even if the multiple myeloma later responds to treatment. (See "Patient information: Renal replacement therapy").

Infection — Bacterial infections, often indicated by the presence of fever, require prompt treatment with antibiotics. Daily use of the antibiotic trimethoprim-sulfamethoxazole (Bactrim) can help prevent infections. Individuals who get frequent infections may be advised to take penicillin daily or rarely to have periodic intravenous infusions of gamma globulin.

All individuals with MM should receive the pneumococcal vaccine (which reduces the likelihood of pneumonia) and the influenza vaccine (which reduces the likelihood of flu). (See "Patient information: Influenza").

Bone pain and fractures — Physical activity, with careful avoidance of injury, can promote bone strength in individuals with MM. The bone pain associated with MM can be controlled with chemotherapy, analgesics (pain relieving drugs), radiation, and bone strengthening drugs such as zoledronic acid (Zometa™) or pamidronate (Aredia™) (commonly referred to as bisphosphonates) that can also reduce the likelihood of fractures.

In individuals who have early signs of bone erosion, bisphosphonates reduce the risk of fractures and reduce bone pain. Therefore, bisphosphonates are recommended for all individuals who have early signs of bone erosions on x-rays. Bisphosphonates are usually given by intravenous infusion every four weeks; this treatment is continued for approximately two years. Zoledronic acid requires infusion times as short as 15 to 30 minutes. These medications may affect kidney function, which should be monitored on a regular basis to avoid this complication.

Dental procedures, such as root canal or extraction of teeth, may be associated with infection or osteonecrosis of the jaw in patients treated with intravenous bisphosphonates. Accordingly, patients should avoid such procedures while taking these agents; any needed dental procedures should be performed before these agents are started.

Spinal cord compression — Spinal cord compression is a medical emergency that requires prompt treatment to prevent irreversible damage, such as paralysis. Initial treatment may consist of radiation and dexamethasone (a steroid) to reduce swelling around the spinal cord; if these measures are not effective, surgery is needed to relieve pressure on the spinal cord.

Anemia — Anemia that is causing symptoms can be treated with erythropoietin (EPO), a substance that stimulates the production of red blood cells. Erythropoietin is usually given by injection one to three times per week. This treatment effectively increases levels of hemoglobin (the protein in red blood cells that helps carry oxygen to the tissues), improves symptoms, and reduces the need for blood transfusion.

Thickening of the blood — Thickening of the blood (called hyperviscosity syndrome) rarely occurs in individuals with MM. This complication is treated with plasmapheresis, a type of blood filtration that removes the excess monoclonal proteins responsible for the increased viscosity.

TREATMENT OF RELAPSED OR REFRACTORY DISEASE — Almost all patients with MM who survive their first cycle of treatment eventually relapse, and a modest percentage are resistant to initial treatment.

MM that responds poorly or not at all to melphalan-prednisone or other chemotherapy is called refractory MM. This condition can occur during initial chemotherapy or during chemotherapy given after a relapse. Refractory MM is more difficult to treat.

Thalidomide, bortezomib, and lenalidomide have all shown significant single-agent activity in relapsed or refractory MM; together with alkylators and corticosteroids, they form the major treatment options for relapsed or resistant disease. Relapses occurring more than six months after completing chemotherapy are usually treated by resuming the initial chemotherapy. Most individuals will again have a response to chemotherapy when it is given a second time, but the response is usually shorter and less marked than the original response. Selected patients can consider autologous or allogeneic stem cell transplantation. The lack of response to initial induction chemotherapy does not always mean that the person will not have good response to autologous hematopoietic cell transplantation. Said another way, if a person does not respond to induction chemotherapy, he or she may still respond to autologous stem cell transplantation.

CLINICAL TRIALS — Progress in treating multiple myeloma requires that better treatments be identified through clinical trials. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies; clinical trials are conducted all over the world. Ask for more information about clinical trials, or read about clinical trials at:

www.cancer.gov/clinical_trials/learning/
www.cancer.gov/clinical_trials/
http://clinicaltrials.gov/


WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. The International Myeloma Foundation

(www.myeloma.org)
Multiple Myeloma Research Foundation

(www.multiplemyeloma.org)
National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Cancer Institute

(www.cancer.gov)
American Cancer Society

(www.cancer.org)
The Leukemia & Lymphoma Society

(www.leukemia-lymphoma.org)
National Marrow Donor Program

(www.marrow.org)
People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)


[1-5]


Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Diagnosis and management of multiple myeloma. Br J Haematol 2001; 115:522.
2. Kyle, RA. Multiple myeloma: an odyssey of discovery. Br J Haematol 2000; 111:1035.
3. Riedel, DA, Pottern, LM. The epidemiology of multiple myeloma. Hematol Oncol Clin North Am 1992; 6:225.
4. Kyle, RA, Rajkumar, SV. Multiple Myeloma. N Engl J Med 2004; 351:1860.
5. Rajkumar, SV, Kyle, RA. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc 2005; 80:1371.