What is WM?

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What Is Waldenstrom macroglobulinemia?

Waldenstrom macroglobulinemia (WM) is a rare, slow-growing cancer of the lymphatic system. Cancers of the lymphatic system are called lymphomas. WM is a type of lymphoma called non-Hodgkin lymphoma. Non-Hodgkin lymphoma is not a single disease; it refers to a group of different lymphomas that start in the lymphocytes (white blood cells). WM affects a specific type of white blood cell, called a B-lymphocyte or B-cell for short.

To understand WM, it’s helpful to know some basic information about your body’s lymphatic system and the function of lymphoid tissue.

What is the lymphatic system?

The lymphatic system is made up of a large network of vessels, organs, and tissues that help your body fight disease and infection. Lymphoid tissue can be found in many places in the body, including:

  • Lymph nodes – small, bean-shaped glands located throughout your body. Some are found in clusters in places like your underarm area, the sides of your neck, your groin, abdomen, and chest.
  • Certain organs – such as your spleen, tonsils, adenoids, and thymus.
  • Bone marrow – the soft, spongy tissue in the center of most bones. This is where new blood cells are made. There are three types of blood cells:
    • Red blood cells, called erythrocytes, carry oxygen throughout the body.
    • Platelets, called thrombocytes, initiate the formation of blood clots to stop bleeding and help with wound healing.
    • White blood cells, called lymphocytes, help the body fight infection and some diseases.

Lymphoid tissue is made mostly of white blood cells, or lymphocytes. There are two types of lymphocytes: B-lymphocytes (B-cells) and T-lymphocytes (T-cells). Normally, B-cells help your body fight infection by maturing into plasma cells. It’s the job of plasma cells to make antibodies – also called immunoglobulins or Ig for short – the proteins that help your body protect itself against infection and other types of threats. There are five main types of antibodies.

How does Waldenstrom macroglobulinemia affect the lymphatic system?

WM is a lymphoma that starts in your B-cells. When a person has WM, there has been a change, or mutation, to their B-cells resulting in the production of an abnormal lymphocyte-plasma hybrid, called a lymphoplasmacytic cell. These abnormal cancer cells multiply over and over again, and can overwhelm the bone marrow leading to a shortage of healthy blood cells in your body.

In WM, these cancer cells make abnormally large amounts of a specific antibody, called IgM. IgM is the largest of all the antibodies, called a macroglobulin. Usually, people have very low levels of IgM in their blood at any given time. With WM, you get high levels of IgM in your blood. Because of IgM’s large size and bulky structure the blood can become very thick, a condition called hyperviscosity. Thick, or viscous blood, cannot flow easily through the body. This can lead to many of the symptoms associated with WM, including excess bleeding, vision problems, cardiovascular complications, and nervous system issues.

What type of lymphoma is Waldenstrom macroglobulinemia?

WM is the most common form of a sub-type of non-Hodgkin lymphoma called lymphoplasmacytic lymphoma (LPL). WM cells are lymphoplasmacytic, meaning they have features of both plasma cells and lymphocyte cells.

WM is a slow-growing lymphoma and does not always require treatment. If you don’t have symptoms, you usually do not need to be treated. If you do develop symptoms, you may need treatment depending on the severity of the symptoms.

Learn the symptoms of WM and discuss any changes with your doctor. While there is no cure for WM yet, there are different types of treatments that can lessen or resolve your symptoms and control the disease for many years.

What are the risk factors for Waldenstrom macroglobulinemia?

A risk factor is anything that increases your chance of developing a disease. You are at higher risk for developing Waldenstrom macroglobulinemia (WM) if you:

  • Are male: WM is more common in men than women.
  • Are White: Caucasians are significantly more likely to develop WM than African Americans.
  • Are older: There are a few cases of WM occurring in younger people, but the chance of developing this disease increases as you age. WM is most often diagnosed in adults age 65 years and older.
  • Have a condition called IgM monoclonal gammopathy of undetermined significance (called IgM MGUS): This is a condition in which you have higher than normal levels of the antibody IgM – detected from blood tests – but no evidence of lymphoma.
  • Have a closely-related family member with WM or another type of lymphoma.
  • Have certain autoimmune diseases like Sjogren’s syndrome, or a viral illness such as hepatitis C. However, the relative importance of these factors has been difficult to determine.

How common is Waldenstrom macroglobulinemia?

WM is a rare disease. About 1,000 to 1,500 people are diagnosed with WM each year in the United States. WM accounts for approximately 1 to 2 percent of all blood (hematologic) cancers.

What causes Waldenstrom macroglobulinemia?

It’s not clear what causes WM. Experts think that changes – or mutations – in the genes of a B-lymphocyte cell is how the disease begins. These mutations tell the abnormal B-cell to continue to multiply uncontrollably. And because cancer cells don’t mature and then die as normal cells do, they accumulate and can overwhelm the production of healthy blood cells.

Recent research has identified two genetic mutations that may be found in people with WM.

  • MYD88 mutation: Most people with WM (about 90 percent) have an abnormal – or mutated – version of a gene known as MYD88.
  • CXCR4 mutations: Up to four out of 10 people with WM have changes to the gene known as CXCR4.

Researchers are studying what causes these genetic changes. They know they are not passed down from your parents. Most of the time, the mutations occur later in life which may explain why WM is usually diagnosed in older people. It’s likely these mutations do not cause WM by themselves, but in combination with other factors.

How is Waldenstrom macroglobulinemia diagnosed?

Waldenstrom macroglobulinemia (WM) is often discovered incidentally when a person gets blood tests done for some other reason or during their annual check-up. Sometimes, people see their doctor complaining of specific symptoms or have a general sense of not feeling well. If signs and symptoms suggest that a person might have WM, a number of tests and exams will be performed to confirm, or rule out, a diagnosis of WM.

Health history and physical exam

Your doctor will start by getting a detailed medical history. He or she will ask questions about your past and current health, including:

  • Any symptoms you are experiencing, particularly those that may be related to WM
  • Any illnesses or surgeries you have had
  • What medications you take, including prescription and over-the-counter medicines
  • What your current lifestyle is like (exercise, diet, tobacco or alcohol use, hobbies, etc.)
  • Your family medical history

Next, your doctor will perform a physical exam, paying special attention to areas of your body that might be involved with WM, like your lymph nodes, spleen, liver and eyes. Your doctor will also order a number of tests.

Blood tests

  • Your doctor will order several blood tests to determine the types and amounts of antibodies in your blood. People with WM have a high level of the antibody IgM (immunoglobulin M). These blood tests are called:
    • Serum protein electrophoresis
    • Serum immunofixation electrophoresis
    • Serum quantitative immunoglobulins
  • A complete blood count (CBC) is a commonly used blood test. It measures the levels of red blood cells, white blood cells (including lymphocytes), and platelets. Because WM cells may crowd out the production of healthy blood cells in the bone marrow, people with WM often have low blood counts.
  • A comprehensive metabolic panel (CMP) is a panel of blood tests used to determine how well your organs – such as your kidneys and liver – are working.
  • There are other blood tests used to monitor WM, detect complications of the disease, and help predict a person’s prognosis:
    • Serum viscosity: Measures the thickness (viscosity) of the blood. In WM, high levels of IgM in the blood make it thicker than normal.
    • Cryocrit and cold agglutinins: These two tests measure for certain abnormal IgM antibodies seen in some people with WM. These antibodies react to cold temperatures and can affect the level of IgM in the blood.
    • Beta-2 microglobulin: Measures the blood level of a protein called beta-2 microglobulin. It provides information about the severity of the disease; high levels are linked with a worse outlook.

Bone marrow aspiration and biopsy

Since the symptoms of WM can be similar to those caused by other diseases or infections, a diagnosis of WM can only be confirmed by testing your bone marrow. The bone marrow samples are sent to a laboratory to be examined by an expert in diagnosing diseases of the bone marrow and blood, called a hematopathologist. He or she will look for the lymphoplasmacytic cells of WM, which have features of both B-lymphocytes and plasma cells.

If detected, advanced analysis of the bone marrow tissue can further characterize the cells’ characteristics, including their genetic mutations. There are two gene mutations that may be found in people with WM: Most have an abnormal (mutated) version of a gene called MYD88; about 40 percent of people with WM have a mutation of the gene CXCR4; 5% percent will not have a mutation of either of them.

Bone marrow aspiration and biopsy can be done at your doctor’s office or in the hospital. These procedures are performed at the same time, usually on the back of your pelvic  bone. Your doctor will numb the area with a local anesthetic and insert a needle to remove liquid bone marrow with a syringe (aspiration). Then a wider needle will be inserted to remove a small piece of bone and soft marrow (biopsy). You may experience some brief pain, tenderness, or bruising at the biopsy site. Most people go home following the procedure.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce detailed pictures of the inside of your body. They are not needed to diagnose WM; however, they help your doctor determine whether the cancer has spread beyond your bone marrow to other parts of your body.

The most widely used imaging test for WM is computed tomography (CT). CT scans are useful for detecting signs of cancer in your chest, abdomen , back and pelvis. The scan will show if your lymph nodes, spleen, or other organs are enlarged. Sometimes this is done in combination with a positron emission tomography (PET) scan. A PET scan uses a weak radioactive material, which is helpful in detecting small collections of cancer cells, even if the area looks normal on a CT scan. A magnetic resonance imaging scan (MRI) is used predominantly for the brain and spinal cord.

For a detailed description of the medical tests typically used to diagnose and monitor WM, you can refer to the IWMF booklet, Medical Tests, found in IWMF and Affiliate Publications. This booklet can be particularly useful in helping you understand the implications of your test results.