Waldenstrom macroglobulinemia

Lymphoma is a cancer that affects the lymph system—an essential part of the larger immune system, which helps shield patients from germs and infections. It’s divided into two categories—Hodgkin lymphoma and non-Hodgkin lymphoma. Waldenstrom macroglobulinemia (WM) is a type of non-Hodgkin lymphoma.

How rare is Waldenstrom macroglobulinemia?

WM is a rare cancer—it accounts for only 1 to 2 percent of patients with non-Hodgkin lymphoma, according to the American Cancer Society. For every 1 million people, an estimated three people will develop WM in the United States.

What is Waldenstrom macroglobulinemia?

Like other types of lymphoma, WM starts in white blood cells. WM affects a particular type of white blood cell, called a B-cell. The purpose of B-cells is to make antibodies (proteins that attack bacteria).

WM causes these B-cells to start behaving abnormally, and they start making too much of a specific type of antibody, called immunoglobulin M, or IgM. An excessive amount of this antibody can thicken the blood's consistency and lead to many of the symptoms and complications associated with WM, like bleeding, trouble hearing or seeing and heart or nervous system problems.

B-cells can be found throughout most of the body, which means Waldenstrom macroglobulinemia can start or spread almost anywhere. It most often develops in the bone marrow (the spongy tissue inside some bones where most blood cells are made).

As WM continues to grow, the abnormal B cells can overwhelm healthy blood cells, reducing the number of:

• White blood cells (which fight infection)
• Red blood cells (which carry oxygen throughout the body)
• Platelets (which help the blood clot) 

Low levels of any of these three blood cell types can lead to more symptoms.

WM is not only rare, but it is also a slow-growing cancer that can take years for symptoms to appear. It’s primarily a cancer that affects older adults, with the average age of diagnosis around 70.

Waldenstrom macroglobulinemia survival rate

While WM is generally considered an "incurable" condition, people can often live with the disease for many years—sometimes without treatment (if they aren't experiencing problematic symptoms).

Around 78 percent of people with WM survive five years (or longer) after their diagnosis, according to the National Cancer Institute’s SEER database.

Waldenstrom macroglobulinemia symptoms

WM doesn't always cause noticeable symptoms, which is why it’s sometimes caught during a routine blood test. When WM is symptomatic, there are a multitude of potential symptoms.

Some are similar to the symptoms associated with other types of non-Hodgkin lymphoma, including:

• Weight loss
• Fever
• Night sweats
• Swollen lymph nodes

Other possible symptoms are related to the thickening of the blood, called hyperviscosity, that can occur when WM cells produce an excessive amount of the IgM antibody. Hyperviscosity doesn’t develop in every person with WM, but it can’t be treated with blood thinners when it does occur.

WM symptoms caused by hyperviscosity may include:

• Bleeding in the nose or mouth
• Vision problems
• Headache
• Dizziness
• Poor coordination

People with WM can also develop clumps of the IgM antibodies in their extremities (where the body's temperature is lower), causing pain in places like the hands, feet, nose or ears. IgM antibodies can also accumulate in certain organs and lead to complications in the heart or kidneys.

Many of the other potential symptoms are related to the buildup of WM cells in different parts of the body. The cancerous cells are often concentrated in the bone marrow, which means they can interfere with the production of new blood cells and prompt a drop in blood cell counts. A shortage of red blood cells (anemia) is one of the most common outcomes of WM, which may lead to fatigue and weakness.

Depending on where WM cells accumulate, people with WM may also develop swelling in their liver, spleen or lymph nodes.

WM causes

Cancer is caused by changes to our genetic code (DNA) called mutations. Some mutations can be inherited (passed down from parent to child) or brought on by environmental exposures (like smoking cigarettes).

But many genetic changes arise randomly when one of the trillions of cells in the body divide. When a cell divides into two, it has to copy its DNA. Sometimes, the DNA is copied incorrectly, and a mutation appears.

Mutations can cause cancer when they change the way our cells behave. For example, a cancer-causing mutation may spur rapid cell growth and division or prevent cells from dying when they are supposed to.

When these types of mutations occur within the DNA of white blood cells, they can become lymphoma cells. WM occurs when the DNA of these lymphoma cells is altered, and they start over-producing the IgM antibody.

• Scientists have now identified two specific gene mutations that seem to be associated with WM, but there are likely many more. Like most cancers, WM is likely caused by a combination of several mutations.
• Around 90 percent of people with WM have a mutation within their cancer cells' DNA on the MYD88 gene. Roughly 30 percent have a mutation in their cancer cells on the CXCR4 gene.
• These mutations are thought to play a role in WM because they signal the cells to keep dividing instead of dying to make room for new cells.

While progress has been made in identifying some of the genetic changes that cause WM, what prompts these changes to occur isn’t well understood.

• Most WM cases are thought to be caused by mutations that are acquired during one's lifetime and are likely caused by the random, unpreventable mutations that arise when cells divide.
• In rarer cases, patients may inherit gene changes from their parents that raise the risk of developing the disease. WM does appear to run in some families—roughly 20 percent of people with the disease have a family member with WM or a related condition.

Waldenstrom macroglobulinemia risk factors

There are also a few risk factors for WM—factors that can make one more likely to develop the disease. WM is more common among people who are:

• Male
• Over 50 years old
• White

It’s also more common among people who have:

• A family history of WM
• Hepatitis C
• Certain autoimmune diseases (like Sjogren’s syndrome)

Waldenstrom macroglobulinemia treatment

Treatment for WM is intended to keep symptoms at bay and guard against complications of the disease. Many people may delay treatment (and avoid treatment side effects) until the condition starts causing bothersome or problematic symptoms.

However, treatment will likely be initiated right away for people with WM who are experiencing symptoms or problems including (but not limited to):

• Hyperviscosity syndrome (thickening of the blood due to an overproduction of the IgM antibody)
• A shortage of red blood cells (anemia)
• Kidney or heart issues
• Nervous system problems

For those who are symptomatic, treatment typically includes chemotherapy and immunotherapy (a therapy that harnesses the power of the immune system to fight cancer)—either on their own or in combination.

The best treatment for an individual with WM can vary depending on their age, other health issues, symptoms and personal preference.

Besides chemotherapy and immunotherapy, other potential treatment options for WM include:

• Targeted therapy
• Plasmapheresis (plasma exchange)
• Stem cell transplant
• Radiation therapy