Information on the following diseases can be found in the Related Disorders section of this report:

• Lymphocytic Leukemia, Chronic

Symptoms of Waldenstrom'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 a result of increased thickness of the blood fluid caused by abnormally high levels of blood protein (peripheral neuropathy). Examination may also reveal enlarged liver, spleen, or lymph nodes. Blurring or vision impairment may also occur due to the lack of blood flow through the blood vessels that serve the retina. The symptoms are quite variable depending on the affect of the thickened (viscose) blood on the organ involved.

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

Waldenstrom'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 100,000 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.

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 and unnecessary 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. Overprotection 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 plasmocytoma, 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).

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 urine 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 lgM 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. More recently, a monoclonal antibody, rituximab, has been found to be effective. Ongoing research is examining combinations of these drugs as well as trials with radioactive monoclonal antibodies.

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

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

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

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.

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

Kipps TJ. Macroglobulinemia. In Lichtman MA, Beutler E, Kipps TJ, Selisohn U, et al. eds. Williams Hematology. 7th ed. McGraw-Hill Companies. New York, NY; 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. McGraw-Hill Companies. New York, NY; 2005:656, 661.

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

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

Gertz, MA. Waldenstrom Macroglobulinemia. A Review of Therapy. International Waldenstrom Macroglobulinemia Foundation (IWMF). 2001.

REVIEW ARTICLES
Lin P, Medeiros LJ. Lymphoplasmacytic lymphoma/waldenstrom 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. Waldenstrom’s macroglobulinemia. Best Pract Res Clin Haematol. 2005;18:689-707.

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

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

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

CONSUMER PUBLICATIONS
Gertz, MA. Waldenstrom Macroglobulinemia. A Review of Therapy. International Waldenstrom Macroglobulinemia Foundation (IWMF). Sarasota, FL:2001.

Rude B, (ed). Treatment Options. A Handbook for Patients. International Waldenstrom Macroglobulinemia Foundation (IWMF), Sarasota, FL;2000:44.

Raushi TM. Waldenstrom Macroglobulinemia. What is it? International Waldenstrom Macroglobulinemia Foundation (IWMF), Sarasota, FL;1999:40.

FROM THE INTERNET
Brose MS. Macroglobulinemia of Waldenstrom. Medical Encyclopedia. Medline Plus. Update Date: 8/3/2004. 3pp.
www.nlm.nih.gov/medlineplus/ency/article/000588.htm

American Cancer Society. Waldenstrom Macroglobulinemia. Revised 10/11/2005. 20pp.
http://documents.cancer.org/162.00/162.00.pdf

National Cancer Institute. Waldenstrom’s Macroglobulinemia: Questions and Answers. nd. 4pp.
www.cancer.gov/cancertopics/factsheet/Sites-Types/WM