Waldenström Macroglobulinemia

Waldenström macroglobulinemia (pronounced “wal-den-strom” “mac-ro-glob-u-lin-e-mia”) is a slow-growing blood cancer. It’s a type of non-Hodgkin lymphoma that also goes by another name: lymphoplasmacytic lymphoma. A rare cancer, Waldenström macroglobulinemia (WM) only affects about 3 to 4 out of every 1 million people in the U.S.

WM happens when B cells (immune cells) in your bone marrow (where blood cells get made) change into cancer cells. The cancer cells copy themselves and can crowd out your normal blood cells. This can lead to low numbers of red blood cells (anemia), white blood cells (neutropenia) and platelets (thrombocytopenia).

The cancer cells also release an abnormal protein called immunoglobulin M (IgM). Too much IgM can thicken your blood, turning it into a syrup-like liquid. This is called hyperviscosity syndrome. The thickened blood doesn’t flow easily through your body’s tiny blood vessels and can cause serious symptoms.

There’s no cure for Waldenström macroglobulinemia. But there are treatments that ease and sometimes eliminate symptoms. As WM tends to progress slowly, it’s possible that you’ll live many years with this condition.

Symptoms of Waldenström macroglobulinemia

One in 4 people diagnosed with WM don’t have symptoms. They learn they have this condition while visiting their healthcare provider for other reasons. When WM does cause symptoms, they come on slowly. Symptoms include:

• Weakness and fatigue
• Fever
• Loss of appetite
• Night sweats
• Weight loss
• Confusion
• Enlarged liver, spleen or lymph nodes
• Signs of peripheral neuropathy (tingling sensation in your fingers and toes)
• Signs of thickened blood (nosebleeds, bleeding gums, dizziness, headaches and blurred vision)

Waldenström macroglobulinemia causes

Genetic mutations cause Waldenström macroglobulinemia. More than 90% of people (9 out of 10) with WM have a mutation involving the MYD88 gene. And about 40% (4 out of 10) have changes to their CXCR4 gene. Both mutations help the abnormal cells in Waldenström macroglobulinemia multiply.

These changes aren’t inherited (hereditary). This means you can’t pass this on to your children, and you didn’t get it from your parents. Instead, they develop during your lifetime. But researchers don’t know what triggers the mutations in the first place.

Risk factors

Factors that may increase your chance of developing Waldenström macroglobulinemia include your:

• Age. Most people diagnosed are 65 and older.
• Race. WM is most common in people who are white.
• Sex. Males are more likely to have WM.
• Medical history. Having hepatitis C, AIDS, Sjögren's Syndrome or MGUS may increase your risk. MGUS is a precursor for WM. But just because you have MGUS doesn’t mean that you’ll develop WM.
• Family’s medical history. Having biological family members who have WM or other kinds of lymphoma may increase your risk.

Complications of this condition

In severe cases, WM can cause complications, including:

• Amyloidosis. This condition happens when faulty proteins build up in organs like your heart, lungs and kidneys.
• Cryoglobulinemia. This condition happens when certain blood proteins that react to cold conditions gather in clumps in your hands and feet. This can cause pain and turn your hands and feet blue or white (cyanosis).

How do doctors diagnose this condition?

Your healthcare provider may use several tests to diagnose Waldenström macroglobulinemia. They look for cancer cells and IgM proteins. Tests include:

• Blood and urine tests. Providers examine blood and urine samples for signs of WM. Signs include low blood cell counts and abnormal IgM proteins.
• Imaging tests. Tests like a CT scan or a combined CT and PET scan (CT-PET) can show signs of WM inside your body. Providers look for things like enlarged organs or lymph nodes.
• Eye exam. This test can check for bleeding in the back of your eyeball. This is a sign of thickened blood.
• Bone marrow biopsy. Providers examine bone marrow samples under a microscope to see if there are cancer cells.

How is Waldenström macroglobulinemia treated?

As there isn’t a cure for this condition, the best treatment is one that relieves symptoms with the least amount of side effects. Your healthcare provider will work with you to customize treatment. Options for WM include:

• Watchful waiting. Your provider may not start treatment if you don’t have symptoms. Some people with WM don’t need treatment for years.
• Plasmapheresis (plasma exchange). Providers use a machine to filter abnormal IgM from your plasma, the liquid part of your blood. They return the plasma to your bloodstream. Providers use this treatment to ease symptoms caused by thickening blood.
• Immunotherapy. This treatment uses your body’s immune system to destroy or slow the growth of WM cells. Providers commonly prescribe rituximab (Rituxan^®) alone or with chemotherapy.
• Chemotherapy. Your providers may prescribe cancer-killing medications alone or in combination with immunotherapy.
• Corticosteroids. You may take a steroid, like dexamethasone, along with immunotherapy and chemo. This treatment fights cancer and reduces the side effects of treatment.
• Targeted therapy. This treatment blocks proteins that cancer cells use to make more copies. Ibrutinib (Imbruvica^®) and zanubrutinib (Brukinsa^®) are both targeted therapies approved by the U.S. Food and Drug Administration (FDA) to treat WM.
• Stem cell transplant. Providers replace bone marrow affected by abnormal cells with healthy bone marrow. This is uncommon and used only in select people.

When should I seek care?

Contact your healthcare provider if you’ve been diagnosed with WM and have a symptom that’s new or bothering you. If you learn you have this condition, it’s important to ask questions so you know what to expect. Here are a few questions you may want to ask your provider:

• How serious is WM, and how will it affect my life?
• What should I expect in the short term and long term?
• Do I need treatment right away?
• What type of treatment do you recommend?
• What treatment side effects should I expect?

What can I expect if I have this condition?

Everyone’s situation is different, particularly with a condition that progresses slowly like Waldenström macroglobulinemia. Research shows that 66% of people (more than 2 out of 3) are alive 10 years after they’re diagnosed. But life expectancy varies by age. Many people diagnosed over age 65 (the most commonly diagnosed age group) die from causes unrelated to WM.

Your prognosis (likely outcome) depends on lots of factors, including your:

• Age
• Blood test results
• Mutation type (not having an MYD88 mutation sometimes suggests a worse outcome)

If you have questions about your situation, talk to your healthcare provider. They know you and the circumstances that may affect your health.

Is there anything I can do to feel better?

Living with a lymphoma like Waldenström macroglobulinemia often requires major life adjustments. It’s important to take advantage of every resource you can. Talk with your healthcare provider about what foods to eat and what activities will promote self-care.

Reach out to others with rare conditions to combat possible feelings of isolation. You’re not alone in your diagnosis — even if it feels like it at first. Ask your provider to connect you with support groups.