Waldenström’s Macroglobulinemia: Questions and Answers

  • Waldenström’s macroglobulinemia is a rare type of slow-growing, non-Hodgkin’s lymphoma. It causes over-production of a protein called monoclonal macroglobulin antibody.
  • Symptoms include weakness, swollen lymph nodes, severe fatigue, nose bleeds, weight loss, and visual and neurological problems; some patients do not have symptoms.
  • Waldenström’s macroglobulinemia is diagnosed using bone marrow biopsy and blood tests; other techniques may also be used.
  • Treatments for Waldenström’s macroglobulinemia in patients with symptoms may include plasmapheresis, chemotherapy, and/or biological therapy.
  • People with Waldenström’s macroglobulinemia are encouraged to enroll in clinical trials that explore new treatments.
  1. What is Waldenström’s macroglobulinemia?
  2. Waldenström’s macroglobulinemia is a rare, indolent non-Hodgkin’s lymphoma. WM is also called lymphoplasmacytic lymphoma. It starts in plasma cells, which develop from white blood cells called B lymphocytes or B cells.

    B cells are an important part of the body’s immune system. They form in the lymph nodes, spleen, and other lymphoid tissues, including bone marrow. Some B cells become plasma cells, which make, store, and release antibodies. Antibodies help the body fight viruses, bacteria, and other foreign substances.

    In WM, abnormal plasma cells multiply out of control, producing large amounts of a protein called monoclonal macroglobulin antibody. High levels of IgM in the blood cause hyperviscosity, which leads to many of the symptoms of Waldenström’s.

  3. How often does Waldenström’s macroglobulinemia occur?
  4. WM is a rare cancer, with about 1,500 new cases annually in the United States. The incidence of WM is higher in males and higher in whites than in African Americans. Incidence increases sharply with age. The median age at diagnosis is 63.

  5. What are the possible causes of Waldenström’s macroglobulinemia?
  6. The cause of WM is not known. However, hepatitis C infection appears to be a significant risk factor for the development of cryoglobulinemia, which is often associated with WM. Scientists believe genetics may play a role in WM because the disease has been seen to run in families.

  7. What are the symptoms of Waldenström’s macroglobulinemia?
  8. Some patients do not have symptoms. For those who do have symptoms, the most common ones are weakness, severe fatigue, bleeding from the nose or gums, weight loss, and bruises or other skin lesions. Severely high levels of IgM can lead to hyperviscosity syndrome, in which the blood becomes abnormally thick. Symptoms of this syndrome include visual problems and neurological problems. During a physical exam, a doctor may also find swelling of the lymph nodes, spleen, and/or liver.

  9. How is Waldenström’s macroglobulinemia diagnosed?
  10. Initial diagnosis of WM is based on blood test and bone marrow biopsy results. Blood tests are used to determine the level of IgM in the blood and the presence of proteins, or tumor markers, that can indicate WM. For the biopsy, a sample of bone marrow is removed, usually from the hip, through a needle for examination under a microscope. The pathologist looks for certain types of lymphocytes that indicate WM. Flow cytometry is often used to look at markers on the cell surface or inside the lymphocytes.

    Additional tests may be recommended to confirm the diagnosis. A computed tomography scan uses a computer linked to an x-ray machine to create pictures of areas inside the body. This test may be used to evaluate the chest, abdomen, and pelvis, particularly swelling of the lymph nodes, liver, and/or spleen. A skeletal survey can help distinguish between WM and a similar plasma cell cancer, multiple myeloma.

  11. How is Waldenström’s macroglobulinemia treated?
  12. At this time, there is no known cure for WM. However, several treatment options are available to prevent or control the symptoms of the disease.

    Patients who do not have symptoms of WM are usually monitored without being treated; these patients often live for many years before requiring treatment. Patients with symptoms are usually treated with chemotherapy. Biological therapy is also used to treat WM. Promising results have been seen with biological therapy and chemotherapy in combination. An example of combination therapy uses rituximab and fludarabine. Patients with high levels of IgM and hyperviscosity syndrome may undergo plasmapheresis. In this procedure, blood from the patient is removed and circulated through a machine that separates the plasma from other parts of the blood. The red and white blood cells and platelets are returned to the patient, along with a plasma substitute. Plasmapheresis is often followed by chemotherapy.

    Because WM is rare, some doctors may suggest treatments that have been effective in some cases, but are not considered standard treatment and/or are under study in clinical trials. Some of these treatments include:

  13. Where can people get more information about clinical trials?
  14. Participation in clinical trials is an important treatment option for patients with WM. In addition to the trials mentioned in Question 6, the NCI is sponsoring several trials using combinations of agents and therapies.

    People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the NCI’s Cancer Information Service at 1–800–4–CANCER and in the NCI booklet Taking Part in Clinical Trials: What Cancer Patients Need To Know, which can be found at http://www.cancer.gov/publications on the Internet. This booklet describes how research studies are carried out and explains their possible benefits and risks. Further information about clinical trials is available at http://www.cancer.gov/clinicaltrials on the NCI’s Web site. The Web site offers detailed information about specific ongoing studies by linking to PDQ®, the NCI’s comprehensive cancer information database. The CIS also provides information from PDQ.