Multiple Myeloma Health Article

Diagnosis

Blood and urine tests

Often, the original diagnosis of multiple myeloma is made from routine blood tests that are performed for other reasons. Blood tests may indicate:

• anemia
• abnormal red blood cells
• high serum protein levels
• low levels of normal antibody
• high calcium levels
• high blood urea nitrogen (BUN) levels
• high creatinine levels

Urea and creatinine normally are excreted in the urine. High levels of urea and creatinine in the blood indicate that the kidneys are not functioning properly to eliminate these substances.

Protein electrophoresis is a laboratory technique that uses an electrical current to separate the different proteins in the blood and urine on the basis of size and charge. Since all of the multiple myeloma M-proteins in the blood and urine are identical, electrophoresis of blood and urine from a patient with multiple myeloma shows a large M-protein spike, corresponding to the high concentration of monoclonal Ig. Electrophoresis of the urine also can detect Bence-Jones proteins.

Bones

A bone marrow aspiration utilizes a very thin, long needle to remove a sample of marrow from the hip bone. Alternatively, a bone marrow biopsy with a larger needle removes solid marrow tissue. The marrow is examined under the microscope for plasma cells and tumors. If 10% to 30% of the cells are plasma cells, multiple myeloma is the usual diagnosis.

X rays are used to detect osteoporosis, osteolytic lesions, and fractures. Computed tomography (CAT or CT) scans can detect lesions in both bone and soft tissue. Magnetic resonance imaging (MRI) may give a more detailed image of a certain bone or a region of the body.

Treatment team

After the initial diagnosis, the treatment team for multiple myeloma may include a hematologist (a specialist in diseases of the blood) and an oncologist or cancer specialist. If radiation is used in treatment, a radiation oncologist may join the team. The treatment of multiple myeloma involves complex decisions, and obtaining second opinions from additional specialists may be important.

Clinical staging, treatments, and prognosis

Related disorders

Monoclonal gammopathy of undetermined significance (MGUS) is a common condition in which a monoclonal Ig is detectable. However, there are no tumors or other symptoms of multiple myeloma. MGUS occurs in about 1% of the general population and in about 3% of those over age 70. Over a period of years, about 16% to 20% of those with MGUS will develop multiple myeloma or a related cancer called malignant lymphoma.

Occasionally, only a single plasmacytoma develops, either in the bone marrow (isolated plasmacytoma of the bone) or other tissues or organs (extramedullary plasmacytoma). Some individuals with solitary plasmacytoma may develop multiple myeloma.

Clinical stages

The Durie-Salmon system is used to stage multiple myeloma. Stage I multiple myeloma requires all of the following (1 gram = approx. 0.02 pints, 1 deciliter = approx. 0.33 fluid ounces):

• hemoglobin (the oxygen-transporting molecule of red blood cells) above 10 grams/deciliter (g/dl)
• serum calcium below 12 mg/dl
• normal bone structure or only isolated plasmacytoma
• low M-protein, based on established guideline levels of Ig protein chains

Approximately 5% of multiple myeloma cases are not progressing at diagnosis, and may not progress for months or years. This is called smoldering myeloma. These patients have stage I blood chemistry but no symptoms.

Stage II multiple myeloma fits neither stage I nor stage III. Stage III multiple myeloma meets one or more the following criteria:

• hemoglobin below 8.5 g/dl
• serum calcium above 12 mg/dl
• advanced bone lesions
• high M-protein

Each stage is subclassified as A or B, based on serum creatinine indicators of normal or abnormal kidney function. Most patients have stage III multiple myeloma at diagnosis.

Prognostic indicators

Prognostic indicators for multiple myeloma may be used instead of, or in addition to, the staging system described above. Prognostic indicators are laboratory tests that help to define the stage of the disease at diagnosis, and its progression during treatment. These indicators are:

• plasmablastic multiple myeloma (presence of plasmablasts, the precursor malignant plasma cells)
• plasma cell labeling index (the percentage of plasma cells that are actively dividing)
• beta 2-microglobulin, a protein secreted by B-cells that correlates with the myeloma cell mass (also indicates kidney damage)

Treatment

Since multiple myeloma often progresses slowly, and since the treatments can be toxic, the disease may not be treated until M-protein levels in the blood are quite high. In particular, MGUS and smoldering myeloma may be followed closely but not treated. Solitary plasmacytomas are treated with radiation and/or surgery and followed closely with examinations and laboratory tests.

CHEMOTHERAPY.

Chemotherapy, or treatment with anti-cancer drugs, is used for multiple myeloma. MP, a combination of the drugs melphalan and prednisone, is the standard treatment. Usually, the drugs are taken by mouth every 3 to 4 weeks for 6 to 9 months or longer, until the M-protein levels in the blood stop decreasing. MP usually results in a 50% reduction in M-protein.

Dexamethasone, a corticosteroid, sometimes is used to treat the elderly or those in poor health. It can drop the M-protein levels by 40% in untreated individuals and by 20% to 40% in patients who have not responded to previous treatment. Other chemotherapy drugs, including cyclophosphamide, carmustine, doxorubicin, vincristine, and chlorambucil, may be used as well.

Multiple myeloma usually recurs within a year after the end of chemotherapy. Although the chemotherapy can be repeated after each recurrence, it is progressively less responsive to treatment.

Side effects of chemotherapy may include:

• anemia
• hair loss (alopecia)
• nausea and vomiting
• diarrhea
• mood swings
• swelling
• acne

These side effects disappear after treatment is discontinued.

OTHER DRUG TREATMENTS.

Bisphosphonates are drugs that inhibit the activity of osteoclasts. These drugs can slow the progression of bone disease, reduce pain, and help prevent bone fractures. Different types of bisphosphonates inhibit osteoclasts in different ways. They also reduce the production of interleukin-6 by bone marrow cells. Laboratory studies suggest that bisphosphonates may kill or inhibit the growth of multiple myeloma cells. Pamidronate is the most common bisphosphonate for treating multiple myeloma.

The drug thalidomide appears to have several anti-myeloma activities. Thalidomide affects the immune system in various ways and it appears to inhibit myeloma cells, both directly and indirectly. It also inhibits the growth of new blood vessels that are needed by tumors. However, if thalidomide is taken during pregnancy, it can cause severe birth defects or death of the fetus.

The drug allopurinol may be used to reduce high blood levels of uric acid that result from kidney dysfunction. Diuretics can improve kidney function. Infections require prompt treatment with antibiotics.

BONE AND PERIPHERAL BLOOD STEM CELL TRANSPLANTATION.

Bone marrow or peripheral blood stem cell transplantations (PBSCT) are used to replace the stem cells of the bone marrow following high-dosage chemotherapy. Chemotherapy destroys the bone marrow stem cells that are necessary to produce new blood cells. In an autologous transplant, the patient's bone marrow stem cells or peripheral blood stem cells (immature bone marrow cells found in the blood) are collected, treated with drugs to kill any myeloma cells, and frozen prior to chemotherapy. Growth factors are used to increase the number of peripheral stem cells prior to collection. A procedure called apheresis is used to collect the peripheral stem cells. Following high-dosage chemotherapy, the stem cells are reinjected into the individual. In an allogeneic transplant, the donor stem cells come from a genetically related individual such as a sibling.

OTHER TREATMENTS.

Blood transfusions may be required to treat severe anemia.

Plasmapheresis, or plasma exchange transfusion, may be used to thin the blood to treat hyperviscosity syndrome. In this treatment, blood is removed and passed through a machine that separates the plasma, containing the M-protein, from the red and white blood cells and platelets. The blood cells are transfused back into the patient, along with a plasma substitute or donated plasma.

Multiple myeloma may be treated with high-energy x rays directed at a specific region of the body. Radiation therapy is used for treating bone pain.

Alternative and complementary therapies

Interferon alpha, an immune-defense protein that is produced by some white blood cells and bone marrow cells, can slow the growth of myeloma cells. It usually is given to patients following chemotherapy, to prolong their remission. However, interferon may have toxic effects in older individuals with multiple myeloma.

Once multiple myeloma is in remission, calcium and vitamin D supplements can improve bone density. It is important not to take these supplements when the myeloma is active. Individuals with multiple myeloma must drink large amounts of fluid to counter the effects of hyperviscous blood.

Prognosis

The prognosis for individuals with MGUS or solitary plasmacytoma is very good. Most do not develop multiple myeloma. However, approximately 15% of all patients with multiple myeloma die within three months of diagnosis. About 60% respond to treatment and live for an average of two and a half to three years following diagnosis. Approximately 23% of patients die of other illnesses associated with advanced age.

The prognosis for a given individual may be based on the prognostic indicators described above. The median survival for those without plasmablasts, and with a low plasma cell labeling index (PCLI) and low beta 2-microglobulin, is 5.5 years. The median survival for patients with plasmablastic multiple myeloma, or with a high PCLI (1% or greater) and high beta 2-microglobulin (4 or higher), is 1.9 and 2.4 years, respectively. Many multiple myeloma patients are missing part or all of chromosome 13. The deletion of this chromosome, along with high beta 2-microglobulin, leads to a poor prognosis.

With treatment, multiple myeloma may go into complete remission. This is defined as:

• M-protein absent from the blood and urine
• myeloma cells not detectable in the bone marrow
• no clinical symptoms
• negative laboratory tests

However, with very sensitive testing, a few myeloma cells are usually detectable and eventually lead to a recurrence of the disease, in the bone or elsewhere in the body.