Waldenstrom Macroglobulinemia

A type of non-Hodgkin lymphoma (NHL), Waldenstrom macroglobulinemia (WM) is when the cancer cells in the lymphocytes—immune system cells that help the body fight disease—start to produce large amounts of an abnormal protein call macroglobulin. While NHL is considered a cancer of the lymphocytes, the presence of WM cells introduces the addition of a cancer of plasma cells into the body.1

How does Waldenstrom macroglobulenimia develop?

Although there are some known risk factors that can make it more likely to develop WM, it is often not clear exactly how or why these risk factors lead to the development of disease. Scientists know that changes in the DNA of healthy lymphocytes can cause the growth of lymphoma cells. DNA is inherited from parents, therefore these specific changes in the DNA may be due to a genetic risk factor. The DNA changes are not passed at birth, however, and tend to develop later than life, and often with no known cause.2

Scientists have also discovered that some patients with WM also have problems or DNA changes in their other bone marrow cells, as well. Certain cells produced in bone marrow called dendritic cells release a hormone known as interleukin-6 (IL-6) that helps healthy plasma cells and lymphocytes grow. Too much IL-6, however, may be an important contributor to WM.2

Risk factors

There are a few risk factors that have been associated with WM. Still, most people with these risk factors never develop the disease. One such risk factor is an abnormality of the body’s antibody-making cells, known as monoclonal gammopathy of undetermined significance (MGUS). Usually, people with MGUS have no symptoms and have no additional health problems. However, about 1-2% of people with MGUS go on to develop a related cancer each year.3

Other potential risk factors for WM include:3

  • Age: The risk of WM increases with age and rarely occurs in those under 50
  • Race: WM is more common in whites than in African Americans
  • Sex: Men are more likely to develop WM
  • Heredity: Genetics may play a role in the development of WM
  • Hepatitis C: Some studies indicate that chronic hepatitis C infection may increase the risk of WM
  • Autoimmune diseases: Research has also shown that certain autoimmune disease, such as Sjogren syndrome, may increase risk of disease

Symptoms

Though WM does not always cause symptoms, when it does, those symptoms tend to be similar to other types of NHL. Common symptoms can include:4

Other symptoms of WM are caused by the buildup of an abnormal IgM antibody called M protein. M protein can cause the blood to become too thick and can lead to many of the symptoms of WM, including excess bleeding, problems with vision, nervous system problems, and poor circulation in the brain, which can lead to symptoms similar to that of a stroke.1,4

Since WM cells grow mainly in bone marrow, this can lead to low levels of red blood cells, also known as anemia. Anemia can make people feel tired and weak and can also cause low numbers of white blood cells, which makes it harder for the body to fight infection. The numbers of platelets in the blood can also drop, which can cause increased bleeding and bruising.1

Stages of Waldenstrom macroglobulenimia

Unlike other forms of cancer where the disease is staged according to how much it has spread in the body, WM does not get classified in a staging system. Instead, doctors tend to look at other factors, like age, blood cell counts, the amount of IgM in the blood, and the amount of another protein in the blood called beta-2 microglobulin (β2M). Patients with lower levels of IgM and β2M tend to have a better prognosis than those with high levels. Older patients, as well as patients with anemia, tend to have a less positive outlook.5

What is a common prognosis?

Doctors rely on a system to help predict prognosis for patients with WM. Factors that tend to lead to a poorer outcome, such as advanced age, low blood hemoglobin, low platelet count, and high IgM and β2M are taken into account and assessed, and patients are divided into one of three risk groups—low- risk, intermediate risk, and high risk. The level of risk determines a patient’s survival outlook.5

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