Multiple myeloma

Multiple myeloma is a cancer of plasma cells. Plasma cells are a special type of white blood cell that are part of the body’s immune system. Plasma cells normally live in the bone marrow and make proteins, called antibodies, that circulate in the blood and help fight certain types of infections. Plasma cells also play a role in the maintenance of bone, by secretion of a hormone, called osteoclast activating factor, which causes the breakdown of bone. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine. These abnormal antibodies are referred to as paraproteins or monoclonal proteins in the blood (M proteins) or urine (Bence Jones protein).

In multiple myeloma, plasma cells infiltrate the bone marrow, spreading into the cavities of all the large bones of the body. In a majority of patients with multiple myeloma the bones develop multiple holes, referred to as osteolytic lesions, that cause the bones to be fragile and subject to fracture. (1) Osteolytic lesions are caused by the rapid growth of myeloma cells, which push aside normal bone-forming cells, preventing them from repairing general wear and tear of the bones. Multiple myeloma also causes the secretion of osteoclast-activating factor, a substance that contributes to bone destruction.

Other complications of multiple myeloma include kidney problems and decreased bone marrow blood cell production. Kidney problems develop when abnormal proteins produced by the myeloma cells are deposited in the kidneys, clogging the tubules. Decreased bone marrow blood cell production results from the replacement of normal bone marrow cells with abnormal plasma cells, and can lead to problems such as anemia. Patients with multiple myeloma may also have decreased quantities of normal antibodies necessary to fight certain types of infection. Multiple myeloma may be preceded by two precancerous conditions: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. These conditions do not cause symptoms and are generally not treated, but can eventually progress to multiple myeloma. The rate of progression of MGUS to multiple myeloma is roughly 1% per year. Smoldering multiple myeloma carries a higher risk of progression.(2)

In 2008, an estimated 19,920 individuals will be diagnosed with multiple myeloma;3 half of these new diagnoses will occur among individuals over the age of 70 years.4 When multiple myeloma is diagnosed, approximately 70% of patients will have bone involvement with their cancer and one-third will have impaired kidney function. In order to understand the best treatment options available for the treatment of multiple myeloma, it is important to first determine the amount of cancer in the body. Determining the amount, or the stage, of the cancer requires a number of tests. These tests may include the following:(5)

• Measurement of beta-2 microglobulin in the blood. This provides information about tumor mass.
• Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) to measure the amount and type of abnormal myeloma protein in the blood.
• Urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) to measure the amount and type of abnormal myeloma protein in the urine.
• A skeletal survey (a series of x-rays) to detect bone damage.
• Bone marrow aspiration and biopsy. A sample of cells is removed from the bone marrow in order to determine the percentage of myeloma cells in the marrow. The sample also allows doctors to assess specific characteristics of the myeloma cells (such as chromosomal abnormalities) that may influence prognosis.
• A complete blood count (CBC) to identify problems such as anemia.
• Blood tests to measure kidney function.
• Measurement of blood calcium levels. An estimated 15 to 20% of patients with multiple myeloma have hypercalcemia (high levels of calcium in the blood) at the time of diagnosis, due at least in part to myeloma-related bone destruction.1 If left untreated, hypercalcemia can cause excessive thirst, frequent urination, dehydration, constipation, and even coma.

The results of these tests will determine the stage of the disease. In order to learn more about the treatment of myeloma, select the appropriate stage.

Stage I: Tests indicate a low tumor amount. Lab values will fall in the following range: M protein IgG less than 5.0 gm/100 ml serum; IgA less than 3.0 gm/100 ml serum or urine Bence Jones protein less than 4 gm in 24 hours; normal serum calcium, normal bones and hemoglobin over 10.0 gm/100 ml serum.

Stage II: An intermediate tumor mass. Lab values are between Stage I and Stage III

Stage III: Tests indicate a high tumor amount. Lab values fall in the following range: M protein IgG greater than 7.0 gm/100 ml serum; IgA greater than 5.0 gm/100 ml serum; urine Bence Jones protein over 12.0 gm in 24 hours; advanced bone lesions; hemoglobin less than 8.5 gm/100 ml serum or calcium over 12 gm/100 ml serum.

Recurrent/Relapsed: The multiple myeloma has persisted or returned (recurred/relapsed) following treatment.

Within each stage, patients may be furthered classified according to the presence or absence of kidney problems.(6) The subclassification “A” refers to patients with normal kidney function; “B” refers to patients with abnormal kidney function. Kidney function is assessed by blood tests.

REFERENCES:

1. Blade J, Rosinol L. Complications of multiple myeloma. Hematology/Oncology Clinics of North America. 2007;21(6):1231-1246.

2. Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.Hematology/Oncology Clinics of North America. 2007;21(6):1093-113.

3. American Cancer Society. Cancer Facts & Figures 2008. Available at: http://www.cancer.org/docroot/stt/stt_0.asp  (Accessed March 12, 2008).

4. Ries LAG, Harkins D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Eisner MP, Horner MJ, Howlader N, Hayat M, Hankey BF, Edwards BK (eds). SEER Cancer Statistics Review, 1975-2004, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2004/, based on November 2006 SEER data submission, posted to the SEER web site 2007.

5. National Comprehensive Cancer Network.  NCCN Clinical Practice Guidelines in Oncology™: Multiple Myeloma. V.1.2008. © National Comprehensive Cancer Network, Inc. 2005/2006. NCCN and NATIONAL COMPREHENSIVE CANCER NETWORK are registered trademarks of National Comprehensive Cancer Network, Inc.

6. Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller, DG et al. AJCC CancerStaging Manual. 6th ed. New York (NY): Springer-Verlag; 2002.

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