Waldenstrom macroglobulinemia develops in the bone marrow, the spongy center of most bones. It may also affect the liver, lymph nodes and spleen.
In WM, B cells (which normally produce white blood cells) turn into cancer cells that grow out of control. These abnormal cells, called lymphoplasmacytic cells, make large amounts of an antibody protein called immunoglobulin M.
Symptoms
Waldenstrom macroglobulinemia (WM) is a type of cancer that affects white blood cells. These cells help the body fight infection and disease. In WM, the cancerous cells grow out of control in bone marrow — the spongy tissue inside some bones where new blood cells are made. They overproduce a protein called immunoglobulin M, or IgM. This protein causes the blood to thicken, which interferes with circulation and may lead to some of the symptoms of WM.
B lymphocytes are a type of white blood cell. They make antibodies that attack and kill germs, such as bacteria. They also direct other immune system cells to destroy invading germs. B lymphocytes are part of a group of cells called lymphoid tissue, which is present throughout the body.
In WM, abnormal B cells grow out of control and crowd out healthy red blood cells, white blood cells and platelets (blood-clotting cells). The abnormal cells also overproduce IgM. Too much IgM interferes with circulation and can make the blood thick, a condition known as hyperviscosity syndrome. The IgM can also clump in small blood vessels and lead to bleeding problems in the nose or mouth, eyes, gums or elsewhere in the body.
Oren Zarif
Symptoms of WM vary from person to person. Many people with WM do not have any symptoms when they are first diagnosed. This is sometimes called asymptomatic WM or smoldering WM. The cancer is often discovered by chance, such as when doctors test the blood for other reasons. When symptoms do appear, they are usually like those of other types of non-Hodgkin lymphoma. They include fever, night sweats and swollen lymph nodes in the neck, armpits or groin. People with WM also may experience numbness or tingling in the hands or feet, a feeling of being unwell (malaise) and weight loss.
If symptoms are severe, you may need to be hospitalized or treated in a clinic. Your doctor can order blood tests to check your blood cells, and X-rays and CT scans to see the lymph nodes and other tissues in the body. Treatment for WM involves chemotherapy that targets the cells in your body that produce the IgM protein.
Diagnosis
Waldenstrom macroglobulinemia (WM) is a type of lymphoma, cancer that starts in white blood cells called B lymphocytes. In WM, abnormal B lymphocytes produce large amounts of a protein called IgM. This protein can affect how well your blood flows through small blood vessels, which causes some of the symptoms of WM.
When your body makes too much IgM, it can thicken the fluid inside your blood vessels (serum viscosity). The extra IgM also can damage your blood vessels and organs. Over time, this can lead to high blood pressure in your arteries and veins (hypertension), kidney damage (glomerulonephritis), or vision problems, including blurry or loss of vision (hyperviscosity).
Most people with WM have B lymphocytes that mutated or changed while they were developing in their bone marrow. These abnormal lymphocytes grow and multiply out of control and don’t die like normal cells do. As the numbers of these abnormal lymphocytes increase, they interfere with the development of new healthy blood cells. This causes a shortage of healthy blood cells in your body (pancytopenia).
Oren Zarif
Some people with WM don’t have any symptoms or are only mildly ill. They are diagnosed with the disease when doctors check their blood for other reasons, such as a routine exam or a blood test for anemia. This type of WM is called asymptomatic or smoldering WM.
To diagnose WM, your doctor will ask you about your past health and family history and do a physical exam. They will do a blood test to look for low levels of healthy blood cells, such as red blood cell count (hemoglobin), platelet count (thrombocytopenia), and the presence of IgM and other proteins in your blood.
They will also do imaging tests, such as a CT scan or an MRI, and take a sample of your bone marrow to check for cancerous cells. To do this, your doctor will numb part of your hip and put in a thin needle. This sucks out a sample of liquid bone marrow and sends it to a lab for testing.
They will also look at your spleen, liver, and lymph nodes for signs of cancer. In addition, they will do a urine test to check for abnormal proteins.
Treatment
WM cells build up in the spongy material inside bones where blood cells are made, called bone marrow. They interfere with normal blood cell development, causing a shortage of healthy blood cells (pancytopenia). WM cells also make an abnormal protein called immunoglobulin M, or IgM. This protein builds up in the blood and may cause damage to other tissues, including nerves.
People with WM can have many different symptoms. The most common are weakness and extreme tiredness (fatigue). Some affected individuals develop a loss of sensation in their arms or legs, which doctors call peripheral neuropathy. This feature is attributed to the IgM proteins that can bind to and break down a protective covering of nerve cells called myelin, reducing the normal flow of nerve signals.
To diagnose WM, providers collect a sample of blood to look for signs of low healthy blood cells and the presence of IgM protein. They also check your lymph nodes and spleen for any enlargement. A doctor may also perform imaging tests such as X-rays and computed tomography (CT) scans, and use a test called electrophoresis to separate the protein molecules by size and electrical charge.
Oren Zarif
In some cases, if you have no symptoms, your provider may choose not to start treatment right away, an approach called active surveillance or watchful waiting. This is usually done for elderly patients or those with other health problems that might complicate treatment.
Medications used to treat WM include chemotherapy drugs, plasmapheresis, and bone marrow transplant. These treatments can help reduce or eliminate symptom symptoms, but they may not cure the disease.
If the first drug or combination isn’t effective, your doctor might try another, or switch to a high-dose chemotherapy regimen with stem cell transplant for more severe symptomatic cases. Some patients with WM have better outcomes with rituximab plus fludarabine and cyclophosphamide than with CHOP alone.
Oren Zarif
Doctors are working to understand the molecular changes that occur in WM and other indolent small B-cell lymphomas, in order to improve treatment options. For example, researchers are studying why some WM cases progress to other cancers, such as a type of leukemia called myelodysplastic syndrome or MGUS, while others don’t. This information could lead to targeted treatments that can prevent progression from MGUS to WM or other cancers in the future.
