June 02, 2021
Years published: 1988, 1989, 1990, 1993, 1995, 1997, 1998, 2002, 2006, 2008, 2012, 2015, 2018, 2021
NORD gratefully acknowledges Morie Gertz, MD, Mayo Clinic, for assistance in the preparation of this report.
Waldenström macroglobulinemia (WMG) is a malignant disorder of the bone marrow and lymphatic tissues, 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 protein known as IgM are produced. Large amounts of IgM cause the blood to become thick (hyperviscosity) and affects the flow of blood through the smaller blood vessels, leading to some of the symptoms of the disorder. Small blood vessels may tear leading to bleeding in the nose, gums, or retina.
Symptoms of Waldenström 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.
The cause of Waldenström macroglobulinemia is unknown. There is evidence of occurrence within families, but such occurrence is uncommon.
Waldenström 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 67. However, patients have been diagnosed in their twenties. This disorder is considerably less common among people of African descent.
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 (analysis of the blood proteins) of serum samples will show a peak reading for IgM. The most common finding preceding the diagnosis is unexplained anemia.
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 preventing complications of hyperviscosity. 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 blood is “reconstituted” by adding previously donated plasma or a plasma substitute. If the disorder progresses, red 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 but are not commonly used today. 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 including bortezomib, Ixazomib, carfilzomib, bendamustine ibrutinib, zanubrutinib and acalbrutinib.
The U.S. Food and Drug Administration (FDA) has approved the use of ibrutinib and zanubrutinib for Waldenstrom macroglobulinemia.
Most people with Waldenström macroglobulinemia have a specific change (mutation) in the MYD88 gene and 30-40% of affected people have a mutation in the CXCR4 gene. These mutations occur in the Waldenstrom cells only and are not inherited. There is some evidence that patients with a CXCR4 mutation are more severely affected and do not respond as well to treatment.
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
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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.
RareConnect offers a safe patient-hosted online community for patients and caregivers affected by this rare disease. For more information, visit www.rareconnect.org.
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American Cancer Society. Waldenström Macroglobulinemia. https://www.cancer.org/cancer/waldenstrom-macroglobulinemia.html Accessed May 17, 2021.
Macroglobulinemia of Waldenström. Medline Plus. U.S. National Library of Medicine.Review Date 5/31/2020. http://www.nlm.nih.gov/medlineplus/ency/article/000588.htm Accessed May 17, 2021.
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