Waldenstrom macroglobulinemia (WM) is a type of non-Hodgkin lymphoma (NHL) . The cancer cells make large amounts of an abnormal protein (called a macroglobulin). Another name for WM is lymphoplasmacytic lymphoma. This condition used to be called Waldenstrom’s macroglobulinemia, so some people refer to it as Waldenstrom’s.

To understand WM, it helps to know about the functions of lymphoid tissue in the body.

Lymphoid tissue and the immune system

Lymphoid tissue is made up several types of immune system cells that work together to help the body resist infections. Lymphoid tissue is found in many places in the body:

• Lymph nodes, which are pea-sized collections of immune system cells throughout the body, including in the underarm area, in the groin, on the sides of the neck, and inside the chest and abdomen
• Bone marrow, the soft inner part of certain bones where new blood cells are made
• The thymus, a small organ behind the chest bone and in front of the heart
• The spleen, an organ on the left side of the abdomen next to the stomach
• The tonsils and adenoids in the throat
• Throughout body systems like the digestive system and respiratory system

Lymphocytes (lymph cells) are the main cells of lymphoid tissue. There are 2 main types of lymphocytes:

• B lymphocytes (B cells) respond to an infection by changing into a different type of cell called a plasma cell. Plasma cells make proteins called antibodies (also called immunoglobulins) that help the body attack and kill disease-causing germs like bacteria.
• T lymphocytes (T cells) help direct immune responses, but they also can kill invading germs directly.

Waldenstrom macroglobulinemia

WM is a cancer that starts in B cells. The cancer cells in people with WM are similar to those of 2 other types of cancer: multiple myeloma and non-Hodgkin lymphoma. Multiple myeloma is considered a cancer of plasma cells, and non-Hodgkin lymphoma is a cancer of lymphocytes. WM cells have features of both plasma cells and lymphocytes and are called lymphoplasmacytoid.

WM cells make large amounts of a certain type of antibody (immunoglobulin M, or IgM), which is known as a macroglobulin. Each antibody (protein) made by the WM cells is the same, so it is called a monoclonal protein, or just an M protein. The buildup of this M protein in the body can lead to many of the symptoms of WM, including excess bleeding, problems with vision, and nervous system problems.

The WM cells grow mainly in the bone marrow, where they can crowd out the normal cells that make the different types of blood cells. This can lead to low levels of red blood cells (called anemia), which can make people feel tired and weak. It can also cause low numbers of white blood cells, which makes it hard for the body to fight infection. The numbers of platelets in the blood can also drop, leading to increased bleeding and bruising.

Lymphoma cells can also grow in organs like the liver and spleen, causing these organs to swell and leading to abdominal pain. (For more on the symptoms of WM, see Signs and Symptoms of Waldenstrom Macroglobulinemia.)

Survival rates are often used by doctors as a standard way of discussing a person’s prognosis (outlook). 

The 5-year survival rate refers to the percentage of patients who live at least 5 years after their cancer is diagnosed. Of course, many people live much longer than 5 years.

Five-year relative survival rates assume that some people with WM will die of other causes and compare the observed survival with that expected for people without WM. This is a better way to see the impact of the cancer on survival.

To get 5-year survival rates, doctors have to look at people who were treated at least 5 years ago. There have been many improvements in the treatment of WM in recent years, so people now being diagnosed with WM may have a better outlook than would be expected based on the numbers below.

According to the National Cancer Institute’s SEER database (based on people diagnosed between 2001 and 2010), the overall relative 5-year survival of people with WM is about 78%.

The group that created the International Prognostic Scoring System for Waldenstrom Macroglobulinemia (ISSWM) used data from about 600 patients with WM who were diagnosed and treated before January 2002 to develop their risk groups:

Median survival

Median survival is another way to look at survival. It is the length of time at which half of the patients in a group are still alive, and half have died. By definition, half of the patients live longer than the median survival. The group that developed the ISSWM used data from WM patients diagnosed and treated before January 2002 and found the following:

*Median survival is measured from the point that treatment is started.

Survival rates are based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen with any particular person. They don’t take into account all of the factors that can affect a person’s outlook, such as how well the cancer responds to treatment. Your doctor knows your situation best and can tell you how the numbers above might apply to you.

Research into the causes, prevention, and treatment of Waldenstrom macroglobulinemia (WM) is being done in many medical centers throughout the world.

Genetics

As noted in Do We Know What Causes Waldenstrom Macroglobulinemia? scientists are making great progress in understanding how changes in DNA can cause normal lymphocytes to develop into WM cells.

For example, in most people with WM, the cancer cells have been found to have changes in the MYD88 gene. More recently, a smaller percentage of WM cells have been found to have changes in the CXCR4 gene. Changes in these genes have been linked with a greater chance of WM causing symptoms and requiring treatment, and seem to affect survival as well.

Researchers are now looking to develop drugs that can target cells with these gene changes. Some of these drugs are now in early clinical trials.

Chemotherapy and targeted therapies

Clinical trials are studying many new drugs to treat WM, as well as ways to use drugs already known to be effective by combining them in new ways, using different doses, or different sequences of drugs, one after another.

Some of the newer types of drugs that have shown promise or are being tested against WM include:

• mTOR inhibitors, such as everolimus (Afinitor) and temsirolimus (Torisel)
• Proteasome inhibitors, such as bortezomib (Velcade), carfilzomib (Kyprolis), and oprozomib
• Histone deacetylase (HDAC) inhibitors, such as panobinostat, romidepsin (Istodax), and belinostat (Beleodaq)
• Bruton tyrosine kinase (BTK) inhibitors, such as ibrutinib (Imbruvica), ACP-196, and AVL-292
• PI3K inhibitors, such as idelalisib (Zydelig) and buparlisib (BKM120)
• Aurora kinase inhibitors, such as alisertib

Biological therapy

Another newer approach to WM treatment is the use of biological response modifiers that stimulate the patient’s immune system to attack and destroy the lymphoma cells.

For example, it has recently been found that the bone marrow support tissues (stromal cells) make a substance called interleukin 6 (IL-6). IL-6 is a strong growth factor for multiple myeloma cells. IL-6 also helps cause the bone destruction seen in myeloma. Some current research efforts are focused on trying to develop ways to block these functions of IL-6, which might lead to new treatments for WM.

Bone marrow and peripheral blood stem cell transplant

Researchers are continually improving bone marrow and peripheral blood stem cell transplant methods, as well as trying to determine how helpful this type of treatment can be for people with WM.

Vaccines

Doctors know it is possible for people with cancer to develop immune responses to their cancer. In rare instances, people’s immune systems have rejected their cancers, and they have been cured. Scientists are now studying ways to boost this immune reaction by using vaccines.

Unlike vaccines used to prevent infections, these vaccines create an immune reaction against the lymphoma cells in patients who have very early disease or whose disease is in remission but could come back or relapse. This is a major area of research in treating lymphomas (including WM), but it is still being tested in clinical trials. You might want to consider enrolling in one of these studies.

Waldenstrom macroglobulinemia (WM) is often found when a person goes to see their doctor because of symptoms they are having, or because they just don’t feel well and go in for a checkup. Sometimes it’s found in people without symptoms when they have blood tests done for some other reason.

If signs or symptoms suggest that a person might have WM, exams and tests will be done to be sure. The most important ones will look for abnormal proteins in the blood and abnormal cells in the bone marrow.

This document is about WM, but it will sometimes discuss ways to diagnose non-Hodgkin lymphoma (NHL). This is because WM is a type of lymphoma. Like other lymphomas, WM can invade the bone marrow, lymph nodes, and other organs.

Medical history and physical exam

If you have signs or symptoms that suggest you might have WM (or another type of lymphoma), your doctor will want to get a thorough medical history, including information about your symptoms, possible risk factors, family history, and other medical conditions.

Next, the doctor will examine you, paying special attention to your lymph nodes and other areas of your body that might be involved, including the eyes, nerves, spleen, and liver. The doctor might also look for signs of infection, which can cause many of the same symptoms.

If the doctor suspects that WM (or another type of lymphoma) might be causing your symptoms, he or she will probably order blood tests as the next step. You might also be referred to a hematologist, a doctor who specializes in diseases of the blood.

Lab tests

WM might be suspected if your doctor finds you have low blood cell counts or unusual protein levels on blood tests. If so, your doctor may order a blood test called serum protein electrophoresis to find out what the abnormal proteins are. It is usually only after these tests are done that a biopsy of either the bone marrow or a lymph node is considered.

Blood cell counts

The complete blood count (CBC) is a test that measures the levels of red blood cells, white blood cells, and platelets. If lymphoma cells occupy too much of the bone marrow, these levels will be low.

Quantitative immunoglobulins

This test measures the levels of the different antibodies (immunoglobulins) in the blood – IgA, IgE, IgG, and IgM – to see if any are abnormally high or low. In WM the level of IgM is high but the IgG level is often low.

Electrophoresis

The abnormal immunoglobulin made in WM is an IgM antibody. This antibody is monoclonal, meaning that it is many copies of the exact same antibody. Serum protein electrophoresis (SPEP) is a test that measures the total amount of immunoglobulins in the blood and finds any monoclonal immunoglobulin. Another test, such as immunofixation or immunoelectrophoresis, is then used to determine the type of antibody that is abnormal (IgM or some other type).

Finding a monoclonal IgM antibody in the blood is needed to diagnose WM. This abnormal protein in WM is known by many different names, including monoclonal immunoglobulin M, IgM protein, IgM spike, IgM paraprotein, M protein, and M-spike. High levels of other types of monoclonal immunoglobulins, like IgA or IgG, are seen in different disorders (like multiple myeloma and some other lymphomas).

Sometimes pieces of the IgM protein are excreted by the kidneys into the urine. These proteins can be detected with a test called urine protein electrophoresis (or UPEP).

Viscosity

Viscosity is a measure of how thick the blood is. If the IgM level is too high, the blood will become thick (viscous) and can’t flow freely (think about pouring honey compared to pouring water).

Cryocrit

This test measures the blood levels of cryoglobulins (proteins that clump together in cool temperatures and can block blood vessels).

Cold agglutinins

Cold agglutinins are antibodies that attack and kill red blood cells, especially at cooler temperatures. These dead cells can then build up and block blood vessels. A blood test can be used to detect these antibodies.

Beta-2 microglobulin (β2M)

This test measures another protein made by the cancer cells in WM. This protein itself doesn’t cause any problems, but it’s a useful indicator of a patient’s prognosis (outlook). High levels of β2M are linked with a worse outlook.

Biopsies

The symptoms of WM and NHL are not distinctive enough for a doctor to know for certain if person has one of them, based on symptoms alone. Most symptoms can also be caused by non-cancerous problems like infections or by other kinds of cancers. Blood tests can help point to the correct diagnosis, but a biopsy (removing samples of affected tissue to look at under a microscope) is the only way to be sure. Several types of biopsies might be used.

Bone marrow aspiration and biopsy

This is the most important type of biopsy for WM, and is needed to confirm the diagnosis. It can be done at the doctor’s office or at the hospital.

The bone marrow aspiration and biopsy are usually done at the same time. The samples are taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breast bone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor cleans the skin over the hip and then numbs the area and the surface of the bone by injecting a local anesthetic. This may briefly sting or burn. A thin, hollow needle is then inserted into the bone, and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed down into the bone. This may also cause some brief pain.

Once the biopsy is done, pressure is applied to the site to help stop any bleeding. There will be some soreness in the biopsy area when the numbing medicine wears off. Most patients can go home right after the procedure.

The bone marrow samples are then sent to a lab, where they are tested to see if they have lymphoma cells (see below). For a diagnosis of WM, at least 10% of the cells in the bone marrow must be lymphoplasmacytoid lymphoma cells.

Fine needle aspiration (FNA) biopsy

In an FNA biopsy, the doctor uses a very thin, hollow needle with a syringe to withdraw a small amount of tissue from a tumor or lymph node. This type of biopsy is useful for sampling lymph nodes to see if they are enlarged because of cancer or another cause such as infection. FNA can help diagnose some lymphomas, but WM is usually diagnosed with a bone marrow biopsy instead.

For an FNA on an enlarged node near the surface of the body, the doctor can aim the needle while feeling the node. If the enlarged node (or tumor) is deep inside the body, the needle can be guided while it is seen on a computed tomography (CT) scan or ultrasound (see the descriptions of imaging tests later in this section).

The main advantage of FNA is that it does not require surgery and can often be done in a doctor’s office. The main drawback is that in some cases it might not get enough tissue to make a definite diagnosis of lymphoma. However, advances in lab tests (discussed later in this section) and the growing experience of many doctors with FNA have improved the accuracy of this procedure.

Excisional or incisional biopsy

For these types of biopsies, a surgeon cuts through the skin to remove an entire lymph node or tumor (excisional biopsy) or a just a small part of a large tumor or lymph node (incisional biopsy). These biopsies are rarely needed in people with WM because the diagnosis is usually made with a bone marrow biopsy. They are used more often for other types of lymphoma.

If the area to be biopsied is near the skin surface, this can be done using local anesthesia (numbing medicine). If the area is inside the chest or abdomen, general anesthesia or deep sedation is used (where the patient is asleep). These types of biopsies almost always provide enough tissue to diagnose the exact type of lymphoma.

Fat pad fine needle aspiration

This type of biopsy may be used in some people with WM to check for amyloid. In this procedure, a thin, hollow needle with a syringe attached is inserted into an area of fat (usually under the skin of the abdomen/belly). A small amount of fat is removed and sent to the lab for testing.

Lab tests on biopsy specimens

All biopsy specimens are looked at under a microscope by a pathologist – a doctor with special training in using lab tests to diagnose diseases. In some cases, a hematopathologist, a doctor with further training in diagnosing blood and lymph node diseases, might also look at the biopsy. The doctors look at the size and shape of the cells and how the cells are arranged. Sometimes just looking at the cells doesn’t provide a clear answer, so other lab tests are needed.

Immunohistochemistry

In this test, a part of the biopsy sample is treated with special man-made antibodies that attach to cells only if they contain specific molecules. These antibodies cause color changes, which can be seen under a microscope. This test may help tell different types of lymphoma from one another and from other diseases.

Flow cytometry

In this test, cells are treated with special man-made antibodies. Each antibody sticks only to certain types of cells. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will make them give off light, which is measured and analyzed by a computer.

This is the most common test for immunophenotyping – classifying lymphoma cells according to the substances (antigens) on their surfaces. Different types of lymphocytes have different antigens on their surface. These antigens also change as each cell matures.

This test can help show whether a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. It has become very important in helping doctors determine the exact type of lymphoma so they can select the best treatment.

Cytogenetics

Doctors use this technique to look at the chromosomes (long strands of DNA) inside lymphoma cells. Cells (usually from the bone marrow) are first grown in the lab. Then the chromosomes are stained and looked at under a microscope. Because it takes time for the cells to start dividing, this test can take weeks.

In some lymphomas, the cells may have too many chromosomes, too few chromosomes, missing parts of chromosomes (called deletions), or other abnormalities. These changes can help identify the type of lymphoma. In WM, deletions are the most common type of chromosome change.

Molecular genetic tests

Molecular tests such as fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) are not usually needed to diagnose WM, but they are sometimes used to diagnose other types of NHL. These tests look at the cells’ DNA without having to grow the cells in the lab first. The tests can give results in less time than cytogenetics and can be done on cells from different sources (like lymph nodes, blood, and bone marrow). They are generally used to look for specific chromosome or gene changes, not just any change.

More testing information

See our document Testing Biopsy and Cytology Specimens for Cancer to learn more about different types of biopsies and lab tests used to diagnose cancer and what the results can tell you.

Imaging tests

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive particles to produce pictures of the inside of the body. These tests are not needed to diagnose WM, but one or more of them might be done to help show the extent of the disease in the body.

Chest x-ray

An x-ray might be done to look at the chest for enlarged lymph nodes.

Computed tomography (CT) scan

The CT scan uses x-rays to make detailed cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs). This scan can help show if any lymph nodes or organs in your body are enlarged. CT scans are useful for looking for signs of lymphoma in the chest, abdomen, and pelvis.

Before the test, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye to better outline abnormal areas in the body. You might need an IV line through which the contrast dye is injected. The injection can cause some flushing (a feeling of warmth, especially in the face). Some people are allergic to the dye and get hives or a flushed feeling or, rarely, have more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies (especially iodine or shellfish) or have ever had a reaction to any contrast material used for x-rays. Medication can be given to help prevent and treat allergic reactions.

A CT scanner has been described as a large donut, with a narrow table that slides in and out of the middle opening. You need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and some people might feel a bit confined by the ring while the pictures are being taken.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle into a suspicious area. For this procedure, the patient lies on the CT scanning table while the doctor moves a biopsy needle through the skin and toward the area. CT scans are repeated until the needle is in the right place. A biopsy sample is then removed and sent to the lab to be looked at under a microscope.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans make detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. This test is rarely used in WM, but if your doctor is concerned about the brain or spinal cord, MRI is very useful for looking at these areas.

Sometimes a contrast material is injected into a vein to make some structures clearer. This contrast is not the same as the contrast used for CT scans, but allergic reactions can still occur. Again, medicine can be given to prevent and treat allergic reactions.

MRI scans take longer than CT scans – often up to an hour. You may have to lie inside a narrow tube, which is confining and can upset some people. Newer, more open MRI machines might be another option. The machine makes loud buzzing and clicking noises that some people find disturbing. Some places provide headphones or earplugs to help block this noise out.

Ultrasound

Ultrasound uses sound waves and their echoes to make pictures of internal organs or masses.

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver, spleen, and kidneys. (It can’t be used to look at organs or lymph nodes in the chest because the ribs block the sound waves.) It is sometimes used to help guide a biopsy needle into an enlarged lymph node.

For this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with a gel). It gives off sound waves and picks up the echoes as they bounce off the organs. A computer then converts the echoes into a black and white image on a screen.

This is an easy test to have, and it uses no radiation. For most ultrasounds, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.

Positron emission tomography (PET) scan

For a PET scan, a radioactive sugar (known as FDG) is injected into the blood. (The amount of radioactivity used is very low and will pass out of the body in a day or so.) Because cancer cells in the body grow quickly, they absorb large amounts of the sugar. You then lie on a table in the PET scanner for about 30 minutes while a special camera creates a picture of areas of radioactivity. The picture is not detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

PET scans can help tell if an enlarged lymph node contains lymphoma or not. It can also help spot small areas that might be lymphoma, even if the area looks normal on a CT scan. These tests can be used to tell if a lymphoma is responding to treatment. They can also be used after treatment to help decide whether an enlarged lymph node still contains lymphoma or is merely scar tissue.

Many medical centers now use a machine that combines the PET scan with a CT scan (PET/CT scan). This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan.

For most types of cancer, determining the stage of the cancer is very important. The stage of a cancer is a summary of how far it has spread. This can be helpful in predicting outcomes and in deciding on treatment.

There is no standard staging system for Waldenstrom macroglobulinemia (WM) based on the extent of the disease in the body because this hasn’t been shown to be important when looking at outcomes or deciding on treatment.

Instead, doctors look at other factors, such as age, blood cell counts, the amount of immunoglobulin (IgM) in the blood, and the level of another protein in the blood called beta-2 microglobulin (β2M). People with lower levels of IgM and β2M tend to do better than those with higher levels. People with WM who are older, are anemic (based on a low blood hemoglobin level), or have a low blood platelet count tend to have a poorer outlook.

Experts have used these factors to develop a system that helps predict prognosis (outlook) for patients with WM. It is called the International Prognostic Scoring System for Waldenstrom Macroglobulinemia (ISSWM). This system takes into account the factors that seem to predict a poorer outcome, such as:

• Age more than 65 years old
• Blood hemoglobin level 11.5 g/dL or less
• Platelet count 100,000/mcL or less
• Beta-2 microglobulin more than 3 mg/L
• Monoclonal IgM level more than 7 g/dL

Except for age, each of these factors is worth a single point. The points are added to make a score, which is used to divide patients into 3 risk groups:

• The low-risk group includes patients 65 or younger who have no more than 1 point.
• The intermediate-risk group includes those who are older than 65 with 2 or fewer points, and those younger than 65 who have 2 points.
• The high-risk group includes those of any age who have at least 3 points.

These groups can be used to help predict survival (discussed in more detail in Survival Rates for Waldenstrom Macroglobulinemia).

Sometimes, Waldenstrom macroglobulinemia (WM) isn’t causing any symptoms when it’s first found. Instead, it’s found when the person has blood tests done for some other reason. WM found this way is sometimes called asymptomatic or smoldering WM.

When WM does cause symptoms, some of them can be like those seen with other types of non-Hodgkin lymphoma (NHL). For example, weight loss, fever, night sweats, and swollen lymph nodes can be seen in many types of NHL.

Other WM symptoms are caused by the large amounts of abnormal IgM antibody (M protein) made by the cancer cells:

• In hyperviscosity syndrome, too much of the M protein in the blood can cause it to become too “thick.” (This is not the kind of thickness that can be treated with drugs known as blood thinners.) When the blood gets too thick, it has trouble moving through blood vessels. This can cause problems such as poor circulation to the brain, which can lead to symptoms like those from a stroke.
• If the M protein only thickens the blood in cooler parts of the body (like in the tip of the nose, ears, fingers, and toes), it is called a cryoglobulin. Cryoglobulins can cause pain or other problems in these areas if a person is exposed to cooler temperatures.
• A condition called amyloidosis can occur when a part of the IgM antibody (called the light chain) builds up in organs like the heart and kidneys. This buildup can lead to heart and kidney problems.

Not all people with WM develop hyperviscosity, cryoglobulins, or amyloidosis.

Common symptoms of WM

Weakness: This is one of the most common symptoms of WM. It can be caused by anemia (too few red blood cells), which can happen when the WM cells crowd out normal cells in the bone marrow. Some people also feel weak when the blood thickens from the buildup of the abnormal protein.

Loss of appetite: Some people with WM lose their appetite.

Fever, sweats, weight loss: WM, like other lymphomas, can cause fevers (without an infection), drenching night sweats, and weight loss (without trying). Together, these are called B symptoms.

Neuropathy: In some people with WM, the abnormal antibody can attack and damage nerves outside the brain. This can lead to numbness or a painful “pins and needles” sensation in the feet and legs, which is called neuropathy.

Other problems

Enlarged lymph nodes: These usually appear as lumps under the skin around the neck, in the groin, or in the armpits. Enlarged lymph nodes are usually about 1 or 2 inches across. They are seen less often in WM than in most other lymphomas.

Swollen abdomen (belly): WM can sometimes make the spleen or liver bigger, making the belly look swollen. In the upper part of the abdomen, the liver is on the right and the spleen on the left. When the spleen gets larger, it can press on the stomach, which makes people feel full when they eat even a small amount.

Nervous system symptoms: In hyperviscosity syndrome, the thickened blood causes poor brain circulation, leading to problems like headache, confusion, and dizziness. It can also cause symptoms like those seen with a stroke, including slurred speech and weakness on one side of the body. Patients with these symptoms should contact their doctor right away.

Abnormal bleeding: High levels of abnormal antibody can damage blood vessels, which can lead to problems like nosebleeds and bleeding gums.

Vision problems: Bleeding around the small blood vessels inside the eyes or poor circulation in these vessels caused by thickened blood might lead to blurred vision or blind spots.

Kidney problems: High levels of the M protein can damage the kidneys directly or through the development of amyloidosis. When the kidneys don’t work well, excess salt, fluid, and body waste products stay in the blood. This can cause symptoms like weakness, trouble breathing, and fluid buildup in body tissues.

Heart problems: High levels of the M protein can damage heart tissue directly or through the development of amyloidosis, in which the protein builds up in the heart muscle. This weakens the heart, affecting its ability to pump blood. In addition, because the blood of people with WM is thicker than normal, their hearts have to work harder to pump blood throughout the body. This strain can wear down the heart muscle, leading to a condition called congestive heart failure. Symptoms can include heart palpitations, feeling tired and weak, cough, shortness of breath, rapid weight gain, and swelling in the feet and legs.

Infections: The high levels of abnormal antibody in WM can slow the body’s normal antibody production. This makes it harder for the body to resist infections.

Digestive symptoms: In some people with WM, the buildup of the M protein in the intestines can lead to problems such as diarrhea, poor absorption of vitamins, or gastrointestinal bleeding (seen as blood in the stools or dark stools).

Sensitivity to cold: In people with cryoglobulins, exposure to cold temperatures can lead to pain, itching, a bluish color, or even sores on the tip of the nose, ears, fingers, or toes due to reduced blood flow to these areas.

Waldenstrom macroglobulinemia (WM) is rare, with an incidence rate of about 3 cases per million people per year in the United States. About 1,000 to 1,500 people are diagnosed with WM each year in the United States.

WM is almost twice as common in men as it is in women, and it is more common among whites than African Americans.

There are few cases of WM in younger people, but the chance of developing this disease goes up as people get older. The average age at the time of diagnosis of WM is in the mid-60s.

Statistics on survival are discussed in Survival Rates for Waldenstrom Macroglobulinemia.

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some cancer risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed.

Researchers have found a few risk factors that make a person more likely to develop Waldenstrom macroglobulinemia (WM). But most people with these risk factors never develop WM.

Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is an abnormality of antibody-making cells that is related to multiple myeloma and WM. In MGUS, like WM and multiple myeloma, abnormal cells in the bone marrow make large amounts of one particular antibody. This antibody is called a monoclonal (or M) protein, and the condition is called a monoclonal gammopathy.

As long as the patient has no symptoms from the abnormal cells or the M protein they make, the abnormal cells make up less than 10% of the bone marrow, and the amount of abnormal M protein in the blood is not very high (less than 3 g/dl), this condition is called MGUS.

MGUS itself does not cause health problems, but each year about 1% to 2% of people with MGUS go on to develop a related cancer (like multiple myeloma, WM, or lymphoma) or another serious health problem (like amyloidosis).

Age

The risk of WM goes up with age. It is rare among people younger than 50 years old.

Race

WM is more common among whites than among African Americans. In contrast, multiple myeloma is about twice as common among African Americans as white Americans. The reasons for these differences are not known.

Sex

Men are more likely than women to develop this disease. The reason for this is not known.

Heredity

Inherited genes seem to play a role in at least some people who get WM. About 1 in 5 people with WM has a close relative with WM or with a related B-cell disease, such as MGUS or certain types of lymphoma or leukemia.

Hepatitis C

Hepatitis C is caused by infection with a virus (known as the hepatitis C virus, or HCV). Some studies have found that people with chronic hepatitis C infection might be more likely to develop WM than people without the virus. But not all studies have found such a link.

Certain autoimmune diseases

Some research has suggested that people with certain types of autoimmune disease, such as Sjögren (Sjogren) syndrome, might be at higher risk for WM.

Some risk factors can make a person more likely to get Waldenstrom macroglobulinemia (WM), but often it’s not clear exactly how these factors might increase risk.

Scientists have learned how certain changes in the DNA inside normal lymphocytes can make them become lymphoma or multiple myeloma cells. Changes in the DNA of some lymphoma cells can also cause them to make high levels of IgM, which leads to most of the symptoms of WM.

The DNA inside our cells makes up our genes – the instructions for how our cells function. We tend to look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes control when cells grow, divide to make new cells, and die at the right time. Certain genes that help cells grow, divide, or live longer are called oncogenes. Others that slow down cell division or make cells die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA changes from a parent that increase their risk for certain types of cancer. Researchers are studying families that have many cases of WM to try to find the genes that might cause this disorder in some people.

The DNA changes found in WM cells are usually acquired after birth (not passed on from a parent). Some of these acquired changes may have outside causes, but often they occur for no apparent reason. They seem to happen more often as we age, which might help explain why WM usually occurs in older people.

Recent research has found that about 9 times out of 10, WM cells have a mutation (change) in a gene known as MYD88, which normally helps immune system cells signal each other and helps keep them alive. The DNA change in this gene might make it stay turned on all the time, which might help the WM cells survive longer than they should.

Sometimes, WM cells have other kinds of DNA changes. In each human cell, the DNA is packaged in 23 pairs of chromosomes. In some WM cells, a piece of a chromosome is missing. This is called a deletion. The most common chromosome defect seen in WM is a deletion of part of chromosome 6. It’s not clear exactly which genes this might affect. Another type of chromosome defect in WM is called a translocation. In a translocation, a piece of one chromosome becomes attached to a different chromosome. Chromosome changes like these can cause oncogenes to be turned on or tumor suppressor genes turned off.

Researchers have found that some patients with WM have important changes or defects in other bone marrow cells. These changes might also help cancer cells grow. Certain cells in the bone marrow called dendritic cells release a hormone called interleukin-6 (IL-6) that helps normal plasma cells and plasmacytoid lymphocytes grow. Excess IL-6 production by these cells appears to be an important factor in the development of WM.

Scientists are learning about the exact gene changes that cause WM. But even though they have found some of these gene changes, they still do not know why these changes occur.

Most of the risk factors for Waldenstrom macroglobulinemia (WM), such as older age or monoclonal gammopathy of undetermined significance (MGUS), can’t be changed or controlled, so there is no way to prevent cancers that might be related to these risk factors.

Some research suggests that people with hepatitis C might be more likely to develop WM. There is currently no vaccine to prevent hepatitis C, but there are ways to lower your risk of getting it, such as avoiding known risk factors like injection drug use or unprotected sex with many partners. Hepatitis C can also be treated effectively in many cases, although it’s not known how this might affect a person’s risk of WM.

Waldenstrom macroglobulinemia (WM) is not common, and at this time there are no widely recommended screening tests to look for this disease in people without symptoms.

Still, many cases of WM are found early, either when people go to the doctor because of symptoms they are having, or when they have blood tests done for other reasons. The best way to find this cancer early is to see your doctor if you have signs or symptoms that might be caused by this disease.

If Waldenstrom macroglobulinemia (WM) keeps growing or comes back after one kind of treatment, other treatments can often still be helpful. Clinical trials also might offer chances to try newer treatments that could be helpful.

But when a person has tried many different treatments and the WM is no longer getting better, even newer treatments may no longer be helpful. If this happens, it’s important to weigh the possible limited benefits of trying a new treatment against the possible downsides, including treatment side effects. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer — when you have been through many treatments and nothing’s working anymore. Your doctor might offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. Your doctor can estimate how likely it is the cancer will respond to treatments you’re considering. For instance, the doctor may say that more treatment might have about a 1 in 100 chance of working. Some people are still tempted to try this. But it’s important to have realistic expectations if you do choose this plan.

Palliative care

No matter what you decide to do, it’s important that you feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but it is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose — the main goal of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve pain caused by a large tumor. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

Hospice care

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t have treatment for the problems caused by the cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice in Hospice Care.

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends — times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

You can learn more about the changes that occur when treatment stops working, and about planning ahead for yourself and your family, in Advance Directives and Nearing the End of Life.