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Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia (WM) is a type of blood cancer that begins in the white blood cells. It usually progresses very slowly, and patients without symptoms may not require treatment for months, years or potentially ever. WM is classified as a non-Hodgkin lymphoma (NHL) because it first occurs in the B-lymphocytes (B-cells).

 According to the International Waldenstrom’s Macroglobulinemia Foundation (IWMF), less than 1,500 people in the United States are diagnosed with WM each year, making it an extremely rare type of cancer. It is most often diagnosed in individuals who are 65 years of age and above. It is also more common in men than in women.

There are many treatments available for WM, including chemotherapy, immunotherapy and targeted therapy. Recent research has made great strides in the treatment of the disease, and the median survival for patients has been improving with these newer treatments. 

Waldenstrom Macroglobulinemia Definition

What Is the Definition of Waldenstrom Macroglobulinemia?

Waldenstrom macroglobulinemia (WM) is a rare, slow-growing cancer that begins in the white blood cells. It is named “Waldenstrom” because it was discovered by Swedish doctor Jan Gosta Waldenstrom, MD, and “macroglobulinemia” because it creates excess amounts of an abnormal protein called macroglobulin or IgM.

WM develops when there is a mutation to the B-lymphocytes, or B-cells. It is a malignant plasma cell disorder, which causes the bone marrow to produce large numbers of abnormal cancerous B-cells (lymphoplasmacytic cells). These eventually accumulate in the blood enough to crowd out healthy blood cells.

This disease, which is a type of non-Hodgkin lymphoma (NHL), is closely related to lymphoplasmacytic lymphoma.

WM Symptoms and Causes

What Are the Waldenstrom Macroglobulinemia Symptoms?

Because WM progresses slowly in most cases, you may not notice symptoms for months or even years. This type of cancer is often discovered through routine blood tests.

The symptoms of WM, if and when you do experience them, include a condition known as hyperviscosity syndrome. This is when the presence of too much immunoglobulin M causes the blood to become excessively thick, causing circulation issues which can manifest as sudden vision changes, headache, and other neurologic symptoms.

Too much immunoglobulin M can also lead to a condition called amyloidosis, which affects the heart and kidneys and can be fatal.

Other symptoms of WM often include one or more of the following:

  • sweating at night
  • fatigue
  • bleeding from the gums or nose
  • loss of appetite
  • weight loss
  • numbness in extremities

The symptoms of Waldenstrom macroglobulinemia are similar to those of other types of cancer, as well as many other medical conditions. If you have questions or concerns about your health, please consult a healthcare professional.

What Is the Cause of Waldenstrom Macroglobulinemia?

While the exact cause of Waldenstrom macroglobulinemia is not yet fully understood, there are some known connections:

  • MYD88: A mutation to the gene known as MYD88 occurs in roughly 90% of WM cases, according to the American Cancer Society. MYD88 is responsible for helping the body’s immune cells communicate, and it is believed that this mutation causes WM cells to survive for longer than they should.
  • Interleukin-6: Some patients with WM experience defects in the dendritic cells of the bone marrow. These cells produce a hormone known as interleukin-6 (IL-6), which helps plasma cells and lymphocytes grow, but excess production is thought to be a factor in WM cases.
  • Chromosome 6: A deletion (when part of a chromosome is missing) often occurs at chromosome 6 in patients with WM.
  • Monoclonal gammopathy of undetermined significance (MGUS) refers to an abnormality in the cells that make antibodies, wherein large amounts of one particular antibody are created. MGUS has close links to both WM and multiple myeloma, a type of leukemia. While it generally does not cause health problems in itself, a small percentage of people with MGUS eventually develop a blood cancer.

WM Risk Factors

What Are the Risk Factors for Waldenstrom Macroglobulinemia?

There are several known risk factors for developing WM.

  • Age: Most people diagnosed with WM are age 65 or older.
  • Gender: While the reasons for this are not yet clear, men are more likely than women to develop WM.
  • Race/Ethnicity: WM is more common in Caucasians than in people of other races.
  • Genetics: Although the majority of WM cases appear to develop from acquired gene mutations, researchers believe there may be a hereditary component to the disease. If a close relative has been diagnosed with WM or another B-cell lymphoma, your risk may be higher.

WM Diagnosis and Treatment

How Do You Determine a Waldenstrom Macroglobulinemia Diagnosis?

The symptoms of WM (in large part due to how slowly it usually spreads) are often not distinct enough themselves to warrant a diagnosis. If you develop lymphoma symptoms, your doctor will likely recommend a physical exam followed by blood tests and a biopsy to confirm or rule out a diagnosis.

Here is a list of what you might experience:

  • Physical exam: First, your doctor is likely to perform a physical exam, paying special attention to your lymph nodes. They will also likely ask about your symptoms and family medical history.
  • Blood tests: After a physical exam your doctor will likely order a complete blood count (CBC). This test measures the level of red blood cells, white blood cells and platelets in your blood. Your doctor will also test your immunoglobulin levels. With WM, immunoglobulin M levels are high and immunoglobulin G levels are usually low.
  • Bone Marrow Biopsy: If WM is suspected, a bone marrow biopsy is needed to confirm the diagnosis. During the procedure, a local anesthetic is injected to numb the skin and covering of the bone called the periosteum, and then a small amount of bone marrow tissue is withdrawn with a needle (aspiration) and a marrow core (biopsy) is taken from the hip bone. The samples are then evaluated for lymphoma cells.
  • Lymph Node Biopsy: In some cases, your doctor may recommend a lymph node biopsy, although these are less common for WM than other types of lymphoma.

I’ve Been Diagnosed with Waldenstrom Macroglobulinemia, Now What?

Your doctor will help you determine the best immediate course of action. With a rare disease like WM, it is important to consult a specialist. With telemedicine, you may even be able to speak to an expert from the comfort of your own home.

Because WM typically progresses very slowly, patients without symptoms may not need to begin treatment right away. If you’ve been diagnosed with WM but don’t have symptoms, you can expect your doctor to regularly monitor your condition. This will likely be in the form of regular blood tests.

Some patients find that joining a multiple myeloma support group helps them process their diagnosis and learn from others who are on a similar journey.

What Are the Waldenstrom Macroglobulinemia Treatment Options?

There is a range of treatment options for Waldenstrom macroglobulinemia, but most patients will start with chemotherapy and immunotherapy.

  • Chemotherapy uses strong drugs that kill or damage cancer cells. With WM, patients typically receive chemo in cycles, allowing the body to rest between treatments. Chemo drugs commonly used to treat WM include:
    • Alkylating agents: cyclophosphamide (Cytoxan), bendamustine (Treanda)
    • Purine analogs: fludarabine (Fludara), cladribine (2-CdA, Leustatin)
    • Corticosteroids: prednisone, dexamethasone (Decadron)
    • Other chemo drugs: vincristine (Oncovin), doxorubicin (Adriamycin)
  • Immunotherapy helps your body’s immune system become better equipped to fight off cancer. It uses man-made versions of antibodies that target specific cancer cells known as monoclonal antibodies like rituximab (Rituxan), ofatumumab (Arzerra) and alemtuzumab (Campath).
  • Targeted therapies are drugs designed to attack lymphoma cells specifically. They include proteasome inhibitors, like bortezomib (Velcade) and carfilzomib (Kyprolis); mTOR inhibitors such as everolimus (Afinitor); and a BTK inhibitor called ibrutinib (Imbruvica).
  • Plasma exchange, also known as plasmapheresis, can help lessen the viscosity of the blood when too much immunoglobulin M collects in it.
  • Stem cell transplants and radiation therapy are sometimes used in combination with the treatments above. Radiation damages the cancer cells in a localized area to stop them from spreading. Stem cell transplants help your body make new, healthy bone marrow, free of cancerous cells.

Here are a few questions to ask when discussing WM treatment options with your doctor:

  • Do I need to start treatment right away?
  • Which treatment option(s) do you recommend, and why?
  • How long will treatment last?
  • What are the risks or side effects?
  • How will we know the treatment is working?
  • If I don’t need to start treatment immediately, how will you monitor my health?

WM Stages and Survival

What Are the Stages of Waldenstrom Macroglobulinemia?

There is no standard staging system for Waldenstrom macroglobulinemia. Instead, doctors rely on the International Prognostic Scoring System for Waldenstrom Macroglobulinemia (IPSSWM). This scoring system uses points to group patients with WM into cohorts based on age, hemoglobin level, platelet count, beta-2 microglobulin level and serum (blood) monoclonal IgM level.

  • Low-risk patients are age 65 or younger who have one point or fewer.
  • Intermediate-risk patients are either older than age 65 with two or fewer points or younger than age 65 with two points.
  • High-risk patients can be any age, with three or more points.

To learn more about the prognostic scoring system for WM, speak with your doctor. They can answer your questions and provide professional insight.

What is the Waldenstrom Macroglobulinemia Survival Rate?

According to Surveillance, Epidemiology, and End Results (SEER) data, published by the National Cancer Institute, the relative five-year survival rate for people diagnosed with WM is about 78%. This means that approximately 78 out of 100 people diagnosed with WM were still alive five years after their diagnosis. However, these numbers vary by group.

For low-risk patients, the five-year survival rate is 87%. For intermediate-risk patients, it is 68%. For high-risk patients, it is 36%. With medical advancements constantly being made, these figures are likely even higher today. What’s more, according to the International Waldenstrom’s Macroglobulinemia Foundation (IWMF), the median survival of WM patients today is 14 to 16 years after diagnosis.

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