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(Primary Macroglobulinemia; Waldenström Macroglobulinemia)

By James R. Berenson, MD, President and Chief Medical Officer, Institute for Myeloma and Bone Cancer Research

Macroglobulinemia is a plasma cell cancer in which a single clone of plasma cells produces excessive amounts of a certain type of large antibody (IgM) called macroglobulins.

  • Although many people have no symptoms, some people have abnormal bleeding, recurring bacterial infections, and bone fractures due to severe osteoporosis.

  • Blood tests and bone marrow examination are needed to make the diagnosis.

  • Macroglobulinemia is not curable, but progression can be slowed with chemotherapy drugs.

Men are affected by macroglobulinemia more often than women, and the average age at which the disorder appears is 65 years. Its cause is unknown.

Symptoms and Complications of Macroglobulinemia

Many people who have macroglobulinemia have no symptoms, and the disorder is discovered by chance when an elevated level of blood proteins is found during routine blood tests.

Other people have symptoms resulting from interference with blood flow to the skin, fingers, toes, nose, and brain that occurs when the large quantity of macroglobulins thickens the blood (hyperviscosity syndrome). These symptoms include bleeding from the skin and mucous membranes (such as the lining of the mouth, nose, and digestive tract), fatigue, weakness, headache, confusion, dizziness, and even coma. The thickened blood also may aggravate heart conditions and cause increased pressure in the brain. Tiny blood vessels in the back of the eyes can become filled with blood and may bleed, resulting in damage to the retina and impaired eyesight.

People who have macroglobulinemia may also have swollen lymph nodes and an enlarged liver and spleen due to infiltration by cancerous plasma cells. Recurring bacterial infections resulting from inadequate production of normal antibodies may cause fever and chills. Anemia, which may result in weakness and fatigue, occurs when cancerous plasma cells prevent production of normal blood-forming cells in the bone marrow. Infiltration of bones by cancerous plasma cells may cause loss of bone density (osteoporosis), which can weaken bones and increase the risk of fractures.

Some people develop a condition called cryoglobulinemia. Cryoglobulinemia involves the development of antibodies that clog up the blood vessels in cold temperatures.

Diagnosis of Macroglobulinemia

  • Blood tests

  • Additional laboratory tests

Blood tests are done when macroglobulinemia is suspected. The three most useful tests are serum protein electrophoresis, measurement of immunoglobulins, and immunoelectrophoresis (a process by which proteins are separated out from plasma and identified based on the detectable immunologic reactions they produce). The occurrence of specific mutations in a specific gene, MYD88, commonly occur among patients with macroglobulinemia.

Doctors may do other laboratory tests as well. For example, doctors may check a blood sample to determine if the numbers of red and white blood cells and platelets are normal. In addition, serum viscosity, which is a test to check the thickness of the blood, is often done. Blood clotting test results may be abnormal, and other tests may detect cryoglobulins. An examination of a urine sample may show Bence Jones proteins (pieces of abnormal antibodies). A bone marrow biopsy may reveal an increased number of lymphocytes and plasma cells, which helps confirm the diagnosis of macroglobulinemia, and the appearance of these cells helps differentiate this disorder from multiple myeloma.

X-rays may show a loss of bone density (osteoporosis). Computed tomography (CT) may reveal an enlarged spleen, liver, or lymph nodes.

Treatment of Macroglobulinemia

  • Corticosteroids

  • Chemotherapy

  • Monoclonal antibodies

  • Ibrutinib

Often, people need no treatment for many years. However, corticosteroids are often helpful because they change the protein composition of cells, damaging or killing the cancerous cells.

Chemotherapy, usually with chlorambucil or fludarabine, can slow the growth of abnormal plasma cells. Other chemotherapy drugs, such as melphalan or cyclophosphamide, and corticosteroids are sometimes used, alone or in combination. Drugs that work differently from the chemotherapy drugs may be helpful. The monoclonal antibody rituximab is effective at slowing the growth of the abnormal plasma cells. Thalidomide, lenalidomide, pomalidomide, bortezomib, carfilzomib, ibrutinib, and idelalisib are being used with some success, especially when they are used with corticosteroids and/or chemotherapy.

A person whose blood is thickened must be treated promptly with plasma exchange, a procedure in which blood is withdrawn, the abnormal antibodies are removed from it, and the red blood cells are returned to the person (see Plateletpheresis (platelet donation)). However, only a small number of people with macroglobulinemia require this procedure.

The disease remains incurable, but patients typically survive 7 to 10 years.

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