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Waldenström's Macroglobulinemia

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NORD is very grateful to Morie Gertz, MD, Chair of Medicine, Mayo Clinic, for assistance in the preparation of this report.

Synonyms of Waldenström's Macroglobulinemia

Disorder Subdivisions

General Discussion

Waldenström's macroglobulinemia (WMG) is a malignant disorder of the blood, a type of lymphoma and characterized by the presence of abnormally large numbers of a particular kind of white blood cell known as B lymphocytes. As these cells accumulate in the body, excessive quantities of an antibody known as IgM are produced. Large amounts of IgM causes the blood to become thick (hyperviscosity) and affects the flow of blood through the smaller blood vessels, leading to the symptoms of the disorder. The organs fed by these small blood vessels do not receive sufficient blood and oxygen, potentially resulting in partial or complete failure of the organ.

Symptoms

Symptoms of Waldenström's macroglobulinemia usually begin gradually. Common symptoms are fatigue and loss of energy due to anemia. Bleeding from the nose and gums may also occur, and tingling in the fingers and toes is often seen (peripheral neuropathy). Examination may also reveal enlarged liver, spleen, or lymph nodes. Blurring or vision impairment may also occur due to changes in blood flow through the blood vessels that serve the retina. The symptoms are quite variable depending on the effect of the thickened (viscous) blood on the organ involved.

Causes

The causes of Waldenström's macroglobulinemia are unknown. There is evidence of occurrence within families, but such occurrence is uncommon.

Affected Populations

Waldenström's macroglobulinemia is a very rare disorder affecting about 1 in 3.4 million American men and about half that number of American women. The incidence of WMG is estimated to be about 5 per 1,000,000 people over the age of 50. The median age at diagnosis is 63. However, cases have been diagnosed in patients in their twenties. This disorder is considerably less common among people of African descent.

Related Disorders

The disease is classified as a subset of lymphocytic lymphoma and also has characteristics in common with chronic lymphocytic leukemia and multiple myeloma.

Multiple myeloma is characterized by excessive growth (neoplastic proliferation) of plasma cells. Plasma cells are produced in the marrow and eventually enter the blood stream. They are a key component of the immune system and secrete a substance known as M-protein, a type of antibody. Antibodies, also known as immunoglobulins, are produced by the body to combat invading microorganisms, toxins, or other foreign substances. Overproduction of plasma cells in affected individuals results in abnormally high levels of these proteins in the body. In addition, excessive plasma cells may eventually mass together to form a tumor, known as a plasmacytoma, in various sites of the body, especially the bone marrow.

Chronic lymphocytic leukemia is the most common type of leukemia in people over 50 years of age. It is characterized by fatigue, weight loss, repeated infections and enlarged lymph nodes. Small, well-separated, movable, hard nodes usually occur. The number of lymph cells in the peripheral blood and bone marrow is chronically elevated. In the advanced stages of the disease, bone marrow failure is common, resulting in an abnormally low red blood cell count (anemia) and lack of blood platelets (thrombocytopenia).

Standard Therapies

Diagnosis
When patients show symptoms of an enlarged spleen and liver combined with bleeding of the retina, WMG is reasonably suspected. The results of a complete blood count (CBC) usually show low red blood cell counts as well as low platelet counts. In such circumstances, electrophoresis (subjecting blood plasma to an electric impulse) of serum samples will show a peak reading for IgM.

Treatment
With asymptomatic patients, a period of watchful waiting is considered the preferred course. To reduce the blood thickness, plasmapheresis, a method of blood exchange which filters out much of the IgM protein, has been shown to be effective in delaying the need for more aggressive treatment. The blood cells are separated from the liquid component (serum or plasma). The heavy IgM molecules that cause the trouble are discarded with the liquid fraction of the exchange. The red blood cells are "reconstituted" by adding previously donated plasma or a plasma substitute. If the disorder progresses, red blood cell transfusions and/or white blood cell transfusions and/or platelet infusions may be necessary.

Traditional chemotherapeutic agents, particularly chlorambucil (Leukeran), cyclophosphamide (Cytoxan), and/or melphalan (Alkeran) either as single agents or in combination with others, have been used in the management of this disease for over 40 years. The monoclonal antibody, rituximab, has been found to be effective. Ongoing research is examining combinations of these drugs. Many new therapies have been introduced in the past few years and include fludarabine, cladribine, bortezomib,lenalidomide, bendamustine and everolimus.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

A search of the Clinical Trials database maintained by the National Institutes of Health at www.clinicaltrials.gov yields 55 trials for WMG.

Peripheral blood stem transplant and bone marrow transplant, using the patient's own stem cells or marrow and that of related or unrelated donors, has been used but the procedure remains highly controversial.

Organizations related to Waldenström's Macroglobulinemia

NORD offers an online community for this rare disease. RareConnect was created by EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders) to provide a safe space where individuals and families affected by rare diseases can connect with each other, share vital experiences, and find helpful information and resources. You can view these international, rare disease communities at www.rareconnect.org.

References

TEXTBOOKS
Kipps TJ. Macroglobulinemia. In Lichtman MA, Beutler E, Kipps TJ, Selisohn U, et al. eds. Williams Hematology. 7th ed. New York, NY: McGraw-Hill Companies; 2006:1549-60.

Longo DL, Anderson KC. Plasma cell disorders. In: Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison's Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill Companies; 2005:656, 661.

Gertz MA. Waldenström Macroglobulinemia. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:37-38.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1009-1010.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:964-65.

JOURNAL ARTICLES
Gertz MA. Waldenström macroglobulinemia: a review of therapy. Am J Hematol. 2005;79(2):147-57.

Lin P, Medeiros LJ. Lymphoplasmacytic lymphoma/Waldenström macroglobulinemia: an eveolving concept. Adv Anat Pathol. 2005;12:246-55.

Robak T, Korycka A, Kasznicki M, et al. Purine nucleoside analogues for the treatment of hematological malignancies: pharmacology and clinical applications. Curr Cancer Drug Targets. 2005;5:421-44.

Dimopoulos MA, Anagnostopoulos A. Waldenström's macroglobulinemia. Best Pract Res Clin Haematol. 2005;18:689-707.

Gertz MA. Waldenström macroglobulinemia: a review of therapy. Am J Hematol. 2005;79:147-57.

Dimopoulos MA, Kyle RA, Anagnostopoulos A, et al. Diagnosis and management of Waldenström's macroglobulinemia. .J Clin Oncol. 2005;23:1564-77.

Bjorkholm M. Treatment options for Waldenström's macroglobulinemia. Clin Lymphoma. 2005;5:155-62.

INTERNET
American Cancer Society. Waldenström Macroglobulinemia. http://documents.cancer.org/acs/groups/cid/documents/webcontent/003148-pdf.pdf. Last Updated January 31, 2012. Accessed March 20, 2012.

Macroglobulinemia of Waldenström. Medical Encyclopedia. Medline Plus. http://www.nlm.nih.gov/medlineplus/ency/article/000588.htm. Updated April 30, 2010. Accessed March 20, 2012./

National Cancer Institute. Waldenström Macroglobulinemia: Questions and Answers..
www.cancer.gov/cancertopics/factsheet/Sites-Types/WM. Updated September 25, 2007. Accessed March 20, 2012.

Report last updated: 2012/03/20 00:00:00 GMT+0