Waldenstrom’s macroglobulinaemia is a rare blood cancer that grows slowly and affects a special type of white blood cell in the bone marrow. While there is no cure, many people live for years with this condition through careful monitoring and targeted treatments when needed.
What is Waldenstrom’s Macroglobulinaemia?
Waldenstrom’s macroglobulinaemia, often shortened to WM, is a rare form of cancer that begins in certain white blood cells. It is sometimes called lymphoplasmacytic lymphoma, which simply describes the type of cells involved. This condition falls under the broader category of non-Hodgkin’s lymphoma, a group of cancers affecting the lymphatic system, which is part of the body’s defense network against infections.[1]
In WM, a specific type of white blood cell called a B cell undergoes changes that transform it into a cancer cell. B cells normally help fight infections by turning into plasma cells that produce proteins called antibodies. In healthy people, these antibodies attach to germs and help the immune system destroy them. However, in WM, the changed B cells grow out of control and produce too much of a protein called immunoglobulin M (IgM).[2]
The cancer cells build up primarily in the bone marrow, which is the spongy tissue inside bones where blood cells are made. As these abnormal cells accumulate, they crowd out healthy blood cells, making it harder for the body to produce enough red blood cells, white blood cells, and platelets. The cancer cells can also spread to other parts of the body, including lymph nodes and the spleen.[1]
One of the defining features of WM is the excessive production of IgM protein. When too much of this protein builds up in the blood, it can make the blood thicker than normal, like syrup. This condition is called hyperviscosity syndrome. Thickened blood doesn’t flow easily through the body’s tiny blood vessels, which can cause serious problems such as bleeding, vision changes, and nervous system issues.[2]
WM is considered a slow-growing cancer, which means it typically develops gradually over time. Many people with WM may not need treatment right away and can live for many years with careful monitoring. Healthcare providers cannot cure WM, but they have treatments available that can control symptoms and help people maintain a good quality of life.[2]
How Common is This Disease?
Waldenstrom’s macroglobulinaemia is extremely rare. In the United States, only about 1,000 to 1,500 new cases are diagnosed each year. To put this in perspective, only about 3 to 4 out of every 1 million people in the United States develop this condition.[2][8]
In the United Kingdom, there are approximately 4,000 people living with WM. Because it is so uncommon, many people have never heard of it before their diagnosis, which can make the experience more isolating and confusing.[7]
The disease shows clear patterns in who it affects. Most people diagnosed with WM are 65 years old or older, though it can occur in younger adults as well. Men are more likely to develop WM than women. The condition is most commonly found in people who are white, and it appears to affect people of European descent more frequently than other racial or ethnic groups.[2][6]
Because WM is so rare, it can take time to find healthcare providers who are experienced in treating it. Many people with WM benefit from seeking care at specialized cancer centers where doctors have more familiarity with this uncommon condition. Patient support groups and foundations dedicated to WM can also provide valuable connections to experienced specialists and others living with the disease.[3]
What Causes Waldenstrom’s Macroglobulinaemia?
The root cause of Waldenstrom’s macroglobulinaemia lies in changes to the genetic material inside B cells. These changes, called mutations, alter the normal instructions that tell cells how to grow and divide. When these instructions go wrong, cells can multiply uncontrollably and become cancerous.[2]
Scientists have identified specific genetic changes that are very common in people with WM. More than 90 percent of people with this condition—9 out of every 10 patients—have a mutation in a gene called MYD88. Additionally, about 40 percent of people with WM have changes in another gene called CXCR4. Both of these genes normally help cells communicate with each other and regulate their survival. When these genes are mutated, they can get stuck in an “on” position, causing cells to live longer than they should and multiply too rapidly.[2][6]
It’s important to understand that these genetic changes are not inherited from parents, nor can they be passed on to children. The mutations happen during a person’s lifetime, most often in older age. Researchers still don’t know exactly what triggers these genetic changes in the first place. They appear to occur randomly rather than being caused by any specific environmental factor or behavior.[2]
Unlike infectious diseases, WM is not contagious. It cannot be spread from person to person through contact, sharing food or drinks, or any other form of transmission. The disease develops within an individual’s own body due to internal cellular changes.[2]
Who is at Higher Risk?
While anyone can develop Waldenstrom’s macroglobulinaemia, certain factors increase the likelihood of developing this condition. Understanding these risk factors can help people and their healthcare providers stay alert for early signs of the disease, though having risk factors does not guarantee that someone will develop WM.[2]
Age is one of the strongest risk factors. WM is predominantly a disease of older adults, with most people being diagnosed after age 65. It is uncommon in younger adults and rare in children or adolescents. As people age, they accumulate more genetic changes in their cells, which may partly explain why WM becomes more common in older populations.[2]
Biological sex also plays a role. Men are more likely than women to develop WM. The reasons for this difference are not fully understood, but it may relate to hormonal factors or differences in how men’s and women’s immune systems function over time.[2]
Race and ethnicity are significant factors as well. WM occurs most frequently in people who are white, particularly those of European ancestry. People of other racial and ethnic backgrounds can develop WM, but the disease is less common in these populations.[2]
Having certain other medical conditions can increase the risk of developing WM. People with a condition called MGUS (monoclonal gammopathy of undetermined significance) have a higher risk. MGUS is considered a precursor condition to WM, though most people with MGUS never develop WM. Other conditions that may increase risk include hepatitis C infection, AIDS, and Sjögren’s syndrome, an autoimmune disorder that affects moisture-producing glands.[2][6]
Family history matters as well. Having biological family members—parents, siblings, or children—who have WM or other types of lymphoma increases a person’s risk. This suggests that some people may inherit genes that make them more susceptible to developing these cancers, even though the disease-causing mutations themselves are not directly inherited.[2]
Signs and Symptoms of the Disease
One of the challenging aspects of Waldenstrom’s macroglobulinaemia is that it often develops very slowly, and many people have no symptoms at all when first diagnosed. In fact, one in four people with WM don’t notice anything wrong with their health. They often learn they have the condition when blood tests done for other reasons reveal abnormal results.[2][6]
When symptoms do occur, they tend to appear gradually over time rather than suddenly. The most common complaint is persistent tiredness or weakness, known as fatigue. This isn’t the normal tiredness that goes away after a good night’s sleep. Instead, it’s a deep exhaustion that can make everyday activities feel difficult and doesn’t improve with rest. This fatigue happens because the cancer cells crowd out healthy red blood cells, leading to anemia, a condition where the body doesn’t have enough oxygen-carrying cells.[1][2]
Many people with WM experience episodes of night sweats severe enough to soak their nightclothes and bedding. Some people describe it as feeling like they’ve jumped into a swimming pool, needing to change their clothes multiple times during the night. Unexplained fever, loss of appetite, and unintentional weight loss are also common. These symptoms occur because the abnormal cells release substances that affect the body’s temperature regulation and metabolism.[1][6]
Physical changes may become noticeable in certain areas of the body. Swollen lymph nodes, which feel like lumps under the skin in the neck, armpits, or groin, can develop as cancer cells accumulate in these filtering stations of the immune system. Some people feel fullness or discomfort under their left ribs, which happens when the spleen becomes enlarged from cancer cell buildup. The liver can also become enlarged, sometimes causing a feeling of fullness or discomfort on the right side of the abdomen.[1][2]
Nerve-related symptoms affect many people with WM. Peripheral neuropathy causes tingling, numbness, or burning sensations in the hands and feet. This happens because the abnormal IgM protein can damage the nerves that carry signals between the body and the brain. People often describe it as feeling like “pins and needles” or wearing tight gloves or socks. Some also experience painful leg cramps.[1][6]
When blood becomes thickened from too much IgM protein, a range of symptoms related to hyperviscosity syndrome can develop. These include frequent nosebleeds or bleeding gums because the thick blood doesn’t clot properly. Vision problems such as blurriness or difficulty seeing can occur because the thick blood can’t flow easily through the tiny blood vessels in the eyes. Headaches, dizziness, confusion, and difficulty concentrating are also signs that blood isn’t flowing properly to the brain.[1][2]
Some people develop easy bruising even from minor bumps or no apparent injury at all. This happens because WM can reduce the number of platelets, the blood cells responsible for clotting. Shortness of breath and difficulty breathing can develop if anemia becomes severe enough that the body struggles to deliver oxygen to tissues.[1]
Preventing Waldenstrom’s Macroglobulinaemia
Unfortunately, there are no known ways to prevent Waldenstrom’s macroglobulinaemia. Because the disease results from genetic mutations that occur randomly during a person’s lifetime, and researchers don’t know what triggers these mutations, there are no specific lifestyle changes, dietary modifications, or behaviors that have been proven to reduce the risk of developing WM.[2]
Unlike some other cancers that can be prevented through avoiding tobacco, maintaining a healthy weight, or limiting sun exposure, WM doesn’t have established preventable risk factors. The genetic changes that cause WM happen inside cells for reasons that scientists don’t yet fully understand. They are not related to environmental exposures, infections that can be vaccinated against, or controllable lifestyle choices.[2]
There are also no screening tests recommended for the general population to detect WM early. Screening tests are medical tests done on people without symptoms to find disease early when it might be more treatable. Because WM is so rare and develops slowly, routine screening of everyone would not be practical or beneficial. However, people who have MGUS—a condition that sometimes precedes WM—may benefit from regular monitoring with blood tests to check if their condition is progressing.[2]
While WM itself cannot be prevented, staying alert to symptoms and seeking medical attention when unusual signs appear can lead to earlier diagnosis. This is particularly important for people who have risk factors such as a family history of WM or other lymphomas. Being aware of persistent symptoms like unexplained fatigue, night sweats, weight loss, or unusual bleeding can prompt timely medical evaluation.[1]
For people already diagnosed with WM, maintaining overall health is important. While these measures don’t prevent WM, they can help people feel better and may support their body’s ability to tolerate treatments if they become necessary. A balanced diet rich in fruits, vegetables, and whole grains provides nutrients the body needs. Regular physical activity, adapted to individual abilities and energy levels, can help maintain strength and reduce fatigue. Avoiding smoking and limiting alcohol consumption are beneficial for overall health and may help reduce the risk of treatment complications.[18][19]
People with WM should also be vigilant about preventing infections, especially if they are receiving treatment or have low white blood cell counts. Simple measures like frequent hand-washing, avoiding contact with people who are sick, staying up to date with recommended vaccinations (after consulting with healthcare providers), and practicing good hygiene can help protect against infections that could be more serious in people with compromised immune systems.[19][23]
How the Body Changes with This Disease
Waldenstrom’s macroglobulinaemia causes several significant changes in how the body normally functions. Understanding these changes can help explain why certain symptoms occur and why different treatments target specific aspects of the disease.[2]
The most fundamental change happens in the bone marrow. Normally, bone marrow produces a balanced mix of different blood cells: red blood cells to carry oxygen, white blood cells to fight infections, and platelets to help blood clot. In WM, abnormal B cells multiply excessively and take up space in the bone marrow. As these cancer cells accumulate, they physically crowd out the normal blood-producing cells. This leads to three related problems: anemia (too few red blood cells), neutropenia (too few infection-fighting white blood cells), and thrombocytopenia (too few platelets).[2]
When red blood cell production decreases, less oxygen reaches the body’s tissues and organs. This explains why people with WM feel tired, weak, and short of breath—their bodies are literally not getting enough oxygen to function normally. The heart may work harder to pump the oxygen-poor blood around the body, which can cause the heart rate to increase even during rest.[2]
The reduction in healthy white blood cells weakens the immune system’s ability to fight infections. People with WM become more susceptible to bacterial, viral, and fungal infections. Even minor infections that healthy people would easily overcome can become serious. This vulnerability to infections can persist for months or years after treatment, especially with certain types of therapy.[2]
Low platelet counts affect the blood’s ability to form clots. Normally, when a blood vessel is injured, platelets rush to the site and stick together to form a plug that stops bleeding. When platelet numbers are low, this process doesn’t work properly. This explains why people with WM may bruise easily, experience nosebleeds, have bleeding gums, or notice small red or purple spots on their skin where tiny blood vessels have leaked.[2]
The abnormal production of IgM protein creates a unique set of problems. This protein is much larger than other antibodies, and when produced in large quantities, it makes the blood more viscous or thick. Imagine trying to push honey through a thin straw compared to pushing water—the honey flows much more slowly and requires more pressure. Similarly, thickened blood moves sluggishly through the body’s smallest blood vessels. This affects organs that depend on a constant flow of blood, particularly the brain, eyes, kidneys, and extremities.[2]
In the eyes, the thick blood can’t flow properly through the tiny vessels in the retina, leading to blurred vision or other visual disturbances. In the brain, reduced blood flow can cause headaches, dizziness, confusion, and difficulty concentrating. The fingers and toes may feel cold or numb because blood isn’t reaching them efficiently. In severe cases, this can cause tissue damage.[2]
The IgM protein can also directly damage nerves through a process that isn’t fully understood. This leads to peripheral neuropathy, where the long nerves running to the hands and feet don’t function properly. Messages from the brain don’t reach these areas correctly, and sensations from the hands and feet don’t reach the brain properly. This creates tingling, numbness, pain, or weakness in the extremities.[2]
As cancer cells accumulate in lymph nodes, these normally small structures swell and become noticeable as lumps. The same process in the spleen and liver causes these organs to enlarge. An enlarged spleen can cause feelings of fullness or discomfort because it pushes against other organs in the abdomen. It can also trap and destroy blood cells, further worsening anemia and low platelet counts.[2]
In some cases, the abnormal IgM proteins can form deposits in various organs, leading to a condition called amyloidosis. These deposits interfere with normal organ function and can affect the heart, kidneys, liver, and other tissues. Another complication, cryoglobulinemia, occurs when abnormal proteins clump together in response to cold temperatures. These clumps can block small blood vessels, particularly in the hands and feet, causing pain and color changes in these areas when exposed to cold.[2]
The cancer cells also release chemical signals that affect the whole body. These substances can trigger the production of inflammatory molecules that cause fever, night sweats, and weight loss. They also affect the body’s metabolism and the areas of the brain that regulate temperature and appetite, which explains why many people with WM experience these constitutional symptoms even before the disease has caused major changes in blood counts or organ function.[2]
