Waldenstrom's Macroglobulinemia

A Type of Blood Cell Cancer

Human Red blood cells
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Waldenstrom’s macroglobulinemia is a blood cell cancer. White blood cells called B lymphocytes multiply out of control, invading the bone marrow, liver, and spleen. People over age 50 have the highest risk for this type of cancer. It is estimated that about 1,000 to 1,500 people are diagnosed each year with Waldenstrom’s macroglobulinemia in the United States. White males develop this cancer twice as often as black males or white or black females.

Waldenstrom’s macroglobulinemia is somewhat similar to two other types of cancer, multiple myeloma (plasma cell cancer) and non-Hodgkin's lymphoma (a group of cancers of lymphocytes).

The cancerous B lymphocytes in Waldenstrom’s macroglobulinemia produce excessive amounts of a large antibody protein called immunoglobulin M (IgM). This makes the blood thick (hyperviscous), which affects the blood flow through smaller blood vessels to the organs of the body. This causes most of the symptoms of the disease, including nervous system, heart, and vision problems.

Risk factors

Some of the risk factors for Waldenstrom’s macroglobulinemia are:

  • Age – Age is the most significant risk factor. The disease is usually diagnosed in people over age 50.
  • Race – The disease is more common in whites than in African Americans.
  • Gender – Men are more likely to develop this cancer than are women.
  • Monoclonal gammopathy of undetermined significance (MGUS) – In MGUS, there is excess production of an antibody protein (immunoglobulin) by abnormal plasma cells. MGUS is by itself harmless, and there are no symptoms, but about 7% of people with MGUS develop Waldenstrom macroglobulinemia over time.


    Waldenstrom’s macroglobulinemia is usually a slow-moving (indolent) disease, and many individuals with it have no symptoms for a long time. Others have symptoms right away. Some of the symptoms may include:

    • Tiredness and fatigue
    • Loss of appetite
    • Nervous system symptoms such as numbness, tingling, or weakness of a muscle; confusion, dizziness, headaches, stroke-like symptoms
    • Abnormal bleeding, such as frequent nosebleeds or bleeding gums, or bruising easily
    • Blurred vision or blind spots
    • Low grade fever, 100 – 101 F
    • Abnormal swelling, such as swollen lymph nodes or enlarged liver or spleen
    • Kidney problems
    • Heart problems leading to weakness, shortness of breath, and fluid buildup in body tissues
    • More frequent infections


    Sometimes Waldenstrom’s macroglobulinemia may be suspected from the abnormal results of a blood test given for some other reason. If symptoms are present, the first blood test done is usually a complete blood count (CBC), which would show low levels of red blood cells (anemia). Next, blood and/or urine samples will be taken and examined for the abnormal antibody protein (IgM). The blood test is called serum protein electrophoresis (SPEP) and the urine test is called urine protein electrophoresis (UPEP).

    Since the excess IgM can make the blood thick (hyperviscous), the blood viscosity will be checked to see if it needs to be treated. The blood levels of beta-2-microglobulin, another protein produced by the cancer cells, will be also checked.

    A bone marrow biopsy (sample) will be taken to look for cancer cells.


    Staging a cancer means determining its extent. However, there is no standard staging system for Waldenstrom’s macroglobulinemia as there is for most other kinds of cancer. So doctors look at the degree of anemia and the levels of IgM and beta-2-microglobulin in the blood. Having anemia and higher levels of these proteins in the blood can mean a poorer outlook for the individual.


    Waldenstrom’s macroglobulinemia can be treated, but there is no cure for it. Approximately 25% of patients with Waldenström macroglobulinemia have no symptoms or anemia, at the time of presentation. These patients are considered to have indolent, asymptomatic Waldenström macroglobulinemia (also called smoldering Waldenström macroglobulinemia) and should not be treated until symptoms develop.

    Plasma exchange (plasmapharesis) should be the first treatment if the patient has symptoms of hyperviscosity such as mouth or nose bleeding, headaches, blurred vision, dizziness, numbing, changes in vision or changes in mental status. During plasmapharesis, the thick liquid part of the blood (plasma) is removed and replaced with fresh liquid by a machine. Plasmapheresis is helpful in relieving the symptoms, and should be used at the start of treatment while waiting for the chemotherapy drugs to begin working. After plasmapharesis the following chemotherapy combinations may be used: dexamethasone and rituximab plus or minus cyclophosphamide, bendamustine plus rituximab, bortezomib and rituximab with or without dexamethasone.

    If the symptoms are absent or minimal the treatment may consist in the administration of rituximab, given alone or in combination with chemotherapy.


    Treatment and prognosis of Waldenström macroglobulinemia by S Vincent Rajkumar updated on April 9, 2015. http://www.uptodate.com

    Waldenström macroglobulinemia. NCCN Guidelines Version 3.2015  http://www.nccn.org

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