Macroglobulinemia

Macroglobulinemia (Waldenström's 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.

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

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. Others 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 normal blood-forming cells in the bone marrow from being produced. Infiltration of bones by cancerous plasma cells may cause loss of bone density (osteoporosis), which can weaken bones and increase the risk of fractures.

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

See the sidebar What Is Cryoglobulinemia?

Diagnosis

Blood tests are performed when macroglobulinemia is suspected; the three most useful are serum protein electrophoresis, measurement of immunoglobulins, and immunoelectrophoresis.

A doctor may perform other laboratory tests as well. For example, the doctor 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 performed. 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 disease from multiple myeloma.

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

Treatment and Prognosis

Chemotherapy, usually with chlorambucil or fludarabine, can slow the growth of abnormal plasma cells but does not cure macroglobulinemia. Other drugs, such as melphalan or cyclophosphamide, are sometimes used, alone or in combination. Recent results show that the monoclonal antibody rituximab may also be effective at slowing the growth of the abnormal plasma cells.

A person whose blood is thickened must be treated promptly with plasmapheresis, 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 Section 14, Chapter 171). However, only a small number of people with macroglobulinemia require this procedure.

The course of the disorder varies from person to person. Even without treatment, many people survive for 5 years or more.