What is Waldenström's macroglobulinemia?

Waldenström's macroglobulinemia (WM) is an uncommon blood cell cancer that originates from malignant B-cells. It is a slow-growing type of non-Hodgkin lymphoma. Waldenström's mostly forms in the bone marrow and can slow the growth of normal blood cells, which can lead to anemia and a weakened immune system.

•   The disease stems from an abnormality in B lymphocytes in the bone marrow, causing them to overproduce an immunoglobulin protein (IgM) that thickens the blood.
•   Although it resembles multiple myeloma and indolent lymphoma, Waldenström's is a form of lymphoplasmacytic lymphoma, a low-grade (or indolent) type of lymphoma.
•   Not everyone needs to be treated, and some patients benefit from a "watchful waiting" approach.
•   While Waldenström's is incurable and will return despite treatment, many people are able to lead active lives and may experience many years of symptom-free remission after treatment.


Waldenström's is rare. About 2,000 to 3,000 people are diagnosed each year in the United States.

Growth and spread

The condition is usually in bone marrow and therefore it is considered a disease of the whole body. But it can affect the liver, lymph nodes, spleen, peripheral and central nervous systems.

Risk factors

Waldenström's is almost twice as common in men as it is in women. Up to 20% of WM patients have a first or second degree relative with WM or another lymphoma, myeloma or chronic lymphocytic leukemia suggesting a familial predisposition. Up to 20% of WM patients have an Ashkenazi Jewish heritage. The genetic basis for familial or ethnic WM is unknown, and research studies are underway at our center in collaboration with the National Institutes of Health to identify genetic basis for predisposition. The chance of developing Waldenström's increases with age; the average age at which someone is diagnosed is their mid-60s.

Symptoms and signs

Many patients do not have symptoms when they are diagnosed. These individuals may have been discovered due to routine blood or imaging tests. Symptomatic patients may manifest symptoms due to anemia (most common), or other deficiencies in blood counts due to the expansion of WM cells in the bone marrow, enlarged lymph nodes or spleen or manifestations related to the IgM protein made by the WM cells including neuropathy (numbness, tingling, burning or pain) in the extremities, cryoglobulinemia, cold agglutinemia, and rarely kidney, brain or spinal cord involvement.

Waldenström's may start with a very early condition, called a precursor condition.
•   Smoldering Waldenström's Macroglobulinemia (SWM): In this precursor condition, high concentrations of abnormal lymphocytes and plasma cells are found in the bone marrow and secrete M proteins of IgM type but patients are largely without symptoms.
•   Monoclonal Gammopathy of Undetermined Significance (MGUS): Abnormal plasma cells are in the bone marrow – but there is no cancer. The abnormal plasma cells produce monoclonal (M) proteins. In most patients, the amount of M protein changes little over time, and there are no symptoms or problems. In some patients, MGUS may later become a more serious condition or cancer, such as Waldenström's.

Disease-modifying therapies

Our colleagues at our Center for Prevention of Progression of Blood Cancers (CPOP), led by Irene Ghobrial M.D., are studying the genetic and epigenetic factors that characterize conditions that are often precancerous to WM, such as Smoldering Waldenström's Macroglobulinemia and Monoclonal Gammopathy of Undetermined Significance. CPOP’s mission is to understand at the molecular level why some patients go on to develop WM disease, while others do not – and to develop targeted therapies to prevent progression, or even eliminate the disease before it leads to symptoms.


If you are a patient – or the physician of a patient – with a precursor condition and are willing to have samples of blood and cancer cells collected for the CPOP research effort during a medical appointment, or if you would like additional information, please email This email address is being protected from spambots. You need JavaScript enabled to view it. or call 617-582-8664.

Related links

•   Researchers Identify Genetic Mutation Responsible for Most Cases of Waldenström's
•   What Are Precursor Blood Conditions and How Are They Treated?
•   PCROWD Study: Understanding Blood Precursor Conditions