From the National Cancer Institute

Waldenström macroglobulinemia

Introduction

Waldenström macroglobulinemia is a rare type of slow-growing, non-Hodgkin lymphoma (cancer that begins in the cells of the immune system). It causes overproduction of a protein called monoclonal immunoglobulin M (IgM or “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 macroglobulinemia is diagnosed using bone marrow biopsy and blood tests; other techniques may also be used.
Treatments for Waldenström macroglobulinemia in patients with symptoms may include plasmapheresis, chemotherapy, and/or biological therapy.
People with Waldenström macroglobulinemia are encouraged to enroll in clinical trials (research studies) that explore new treatments.

What is Waldenström macroglobulinemia?
Waldenström macroglobulinemia (WM) is a rare, indolent (slow-growing) non-Hodgkin lymphoma (cancer that begins in the cells of the immune system). WM is also called lymphoplasmacytic lymphoma. It starts in 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 (the soft, spongy tissue inside bones). Some B cells become plasma cells, which make, store, and release antibodies. Antibodies help the body fight viruses, bacteria, and other foreign substances.

Lymphoplasmacytic cells are cells that are in the process of maturing from B cells to plasma cells. In WM, abnormal lymphoplasmacytic cells multiply out of control, producing large amounts of a protein called monoclonal immunoglobulin M (IgM or “macroglobulin”) antibody. High levels of IgM in the blood cause hyperviscosity (thickness or gumminess), which leads to many of the symptoms of WM.

How often does Waldenström macroglobulinemia occur?
WM is a rare cancer; about 1,500 new cases occur 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 (half of the cases are diagnosed before age 63, and half are diagnosed after age 63).

What are the possible causes of Waldenström macroglobulinemia?
The exact cause of WM is not known. However, scientists believe that genetics may play a role in WM, because the disease has been seen to run in families.

What are the symptoms of Waldenström macroglobulinemia?
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 (e.g., blurring or loss of vision) and neurological problems (e.g., headache, dizziness, vertigo). During a physical exam, a doctor may also find swelling of the lymph nodes, spleen, and/or liver.

How is Waldenström macroglobulinemia diagnosed?
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 (soft, sponge-like tissue in the center of most bones) is removed, usually from the back of the pelvis bone, through a needle for examination under a microscope. The pathologist (a doctor who identifies diseases by studying cells and tissue under a microscope) looks for certain types of lymphocytes (white blood cells) that indicate WM. Flow cytometry (a method of measuring cell properties using a light-sensitive dye and laser or other type of light) 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 (CT or CAT) 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 (x-rays of the skeleton) can help distinguish between WM and a similar plasma cell cancer, multiple myeloma.

How is Waldenström macroglobulinemia treated?
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 (treatment that stimulates the immune system to fight cancer) 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 (which contains the antibody IgM) from other parts of the blood (red blood cells, white blood cells, and platelets). 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 (research studies). Some of these treatments include:
 

• High-dose chemotherapy with autologous stem cell transplantation— blood-forming stem cells (cells from which all blood cells develop) are harvested (removed) and stored, then given back to the patient following high-dose chemotherapy. The harvested cells may be treated before transplantation to get rid of cancer cells. The transplanted cells travel to the bone marrow and begin to produce new blood cells.
• Splenectomy—surgery to remove the spleen. This procedure has been used in WM patients who have a significantly enlarged spleen. Occasionally, WM patients who have had this procedure have experienced remissions (decrease in or disappearance of signs or symptoms of cancer) lasting for many years. The remissions are believed to be due to the removal of a major source of IgM production.
• Thalidomide and bortezomib—drugs used to treat multiple myeloma, a disease similar to WM. Side effects of thalidomide include constipation, weakness, and peripheral neuropathy (a problem in nerve function that causes pain, numbness, tingling, swelling, and muscle weakness). Both agents are currently being studied in clinical trials for WM.