Waldenstrom Macroglobulinemia

About the Disease

Waldenstrom Macroglobulinemia is a type of hematologic malignancy (cancer of the blood) that was identified in 1944 by Dr. Jan Waldenstrom, a Swedish physician. At any given time, there are approximately 4,000 to 8,600 individuals who have been diagnosed with this rare disease.  It occurs most often in people who are over the age of 65, and it is more common in Caucasians than African-Americans. The cause is unknown, although it probably results from genetic predisposition and environmental factors.

Also called lymphoplasmacytic lymphoma, Waldenstrom’s macroglobulinemia is a cancer that starts in the immune system in cells—B cell lymphocytes—that are produced in the lymphatic tissues and bone marrow. As part of the body’s response to infection, B cells change into plasma cells. Waldenstrom’s macroglobulinemia results when one of these B cells, during the course of normal development into a plasma cell, transforms into a cancer cell, which then multiplies out of control. Multiple myeloma is considered a cancer of plasma cells, and non-Hodgkin lymphoma a cancer of lymphocytes; the cells of Waldenstrom’s macroglobulinemia have features of both.

waldenstrom'sWith Waldenstrom’s macroglobulinemia, the abnormal population of B cell lymphocytes grows in the bone marrow and crowds out cells that normally grow there, including cells that are responsible for making different types of blood cells. As a result, patients with Waldenstrom’s macroglobulinemia have low numbers of red blood cells, white blood cells, and platelets, which can lead to fatigue, frequent infections, and excessive bruising or bleeding. The abnormal lymphocytes can also grow in the liver and spleen, causing the organs to become enlarged, which can result in abdominal pain. A central feature of Waldenstrom macroglobulinemia is that the lymphoma cells overproduce a protein called monoclonal immunoglobulin M (IgM, or macroglobulin) antibody, which circulates in the blood. The excessive amount of circulating IgM can cause the blood to become too thick, leading to a condition called hyperviscosity syndrome.  Overproduction of IgM causes many of the symptoms of Waldenstrom’s macroglobulinemia, including excessive bleeding, problems with vision, and nervous system problems.

Symptoms

Common symptoms of Waldenstrom’s macroglobulinemia include numbness or tingling in the hands or feet, nose bleeding, and fatigue (resulting from anemia). It is possible for a person to be asymptomatic and yet, based on high levels of IgM, be diagnosed as having WM. In some, the disorder may produce few symptoms and develop slowly.

Possible symptoms include:

  • Fatigue Bleeding disorders (nosebleeds, bleeding of the gums, easy bruising of the skin)
  • Enlarged lymph nodes (swollen glands), spleen, or liver
  • Numbness, tingling, or burning pain in the hands and feet
  • Neurologic manifestations (mental status changes; dizziness; headache)
  • Bone pain
  • Heart problems
  • Vision problems (blurred or decreased vision, vision loss in one eye)
  • Hearing loss
  • Weight loss
  • Skin problems (eyelid thickening, lesions)
  • Possible complications include:
  • Changes in mental function, possibly leading to coma
  • Congestive heart failure
  • Gastrointestinal bleeding

Diagnosis

The presence of IgM protein in the blood is a characteristic feature of Waldenstrom macroglobulinemia. It is often discovered during the course of thorough physical exam. However, most people who have this protein do not have a serious disorder. The presence of abnormal IgM without any underlying illness is called monoclonal gammopathy of undetermined significance. The diagnosis of Waldenstrom’s macroglobulinemia is confirmed by performing a bone marrow biopsy to determine whether abnormal lymphocytes are present there. Specialized blood and urine tests are used to detect IgM protein and anemia (low numbers of red blood cells).

Treatment

Waldenstrom’s macroglobulinemia is considered incurable but treatable. Treatment is based on an individual patient’s symptoms and complications. Palliative care is an important component. Duration of survival has increased over the years, with reported median survival of up to 20+ years.

Chemotherapy is used for patients with symptomatic disease. This typically uses alkylating agents such as cyclophosphamide and melphalan—drugs that interact with DNA to prevent cells from reproducing. Sometimes the alkylating agent is paired with a glucocorticoid such as prednisone, which affects protein metabolism and the immune system. Drugs may be combined according to clinical trials designed to examine the effectiveness of new treatments.

Plasmapheresis (plasma exchange) can treat hyperviscosity. This process removes the high levels of IgM and can quickly control symptoms caused by hyperviscosity. Blood is taken from the body intravenously and travels through a machine that separates the cells, platelets, and plasma. The plasma is replaced with a substitute that does not contain the IgM.

Radiation or surgery may be used to treat spleen enlargement. The spleen’s size sometimes can be reduced with radiation, or the spleen may be surgically removed.

Stem cell transplantation may be necessary. This can be autologous (using one’s own cells) or allogeneic (using donor cells).

Novel biological therapies use substances naturally produced in the body. Examples are interferons (proteins in the body that fight viral infections) and gene therapy (enhancing the immune system to defend against cancer).

Thalidomide is used in many active protocols at the Myeloma Institute to inhibit development of new blood vessels that feed cancerous cells.

Learn More about Waldenstrom Macroglobulinemia

For more information about Waldenstrom’s macroglobulinemia, see the International Waldenstrom’s Macroglobulinemia Foundation, American Cancer Society and National Cancer Institute websites.