Waldenstrom's macroglobulinaemia

Waldenström’s macroglobulinaemia (WM) is a rare type of slow-growing non-Hodgkin lymphoma. It develops when a type of white blood cell, called lymphoplasmacytic cells (LPL cells), become abnormal and grow out of control. It is also called lymphoplasmacytic lymphoma.

The abnormal LPL cells build up in the bone marrow and sometimes in the lymph nodes, spleen and other organs. They make large amounts of a protein called IgM, which can make the blood thicker than normal.

WM may not cause symptoms when it is first diagnosed. If there are symptoms, they may include:

  • tiredness
  • bruising or bleeding
  • infections
  • night sweats
  • weight loss
  • headaches
  • blurred vision.

Doctors can diagnose WM with a blood test. You may also have a bone marrow test and a scan to find the extent (stage) of the lymphoma.

WM may not need to be treated for months or years. If you don’t have treatment, you will have regular check-ups instead. The main treatments are chemotherapy, and sometimes targeted therapy. Some people have a treatment called plasma exchange (plasmapheresis). This removes IgM from their blood if it becomes too thick.

What is WM (lymphoplasmacytic lymphoma)?

It is best to read this information with our general information about non-Hodgkin lymphoma (NHL). If you have any more questions, you can ask your doctor or nurse at the hospital where you are having treatment.

Waldenström’s macroglobulinaemia (WM) is a slow-growing type of NHL. It is also called lymphoplasmacytic lymphoma.

WM is a cancer of a type of white blood cell called lymphoplasmacytic cells (LPL cells). This is where the name lymphoplasmacytic lymphoma comes from. LPL cells are a type of white blood cell called a B-cell. This is why WM is also sometimes called a B-cell lymphoma.

In people with WM, the number of abnormal LPL cells (lymphoma cells) increases over time and they begin to fill the bone marrow. This is where blood cells are usually made. Lymphoma cells can also build up in lymph nodes, the spleen and other organs, causing them to get bigger.

The lymphoma cells make large amounts of a protein called immunoglobulin M (IgM). This protein circulates in the blood. Sometimes doctors call it the M-protein or M-band. You may also hear it called a paraprotein.


Causes and risk factors for WM

The causes of WM are unknown. WM is more common in people over 65. It is slightly more common in men than women. People who have MGUS (monoclonal gammopathy of unknown significance), a condition where there is abnormal IgM in the blood, sometimes develop WM.

People who have a family member with lymphoma have a higher than average risk of developing WM. But because WM is rare, their risk of getting it is still very low. Most people who develop WM don’t have any family members with lymphoma. Like other cancers, it is not infectious and can’t be passed on to other people.


Signs and symptoms of WM

WM usually develops over a long period of time. Some people have no symptoms, and the cancer is found by chance following a blood test for some other reason.

Lymphoma cells building up in the bone marrow can cause symptoms. This is because the lymphoma cells take up space, which makes it difficult for the bone marrow to make enough blood cells.

The most common symptoms are:

  • feeling weak and tired (fatigue)
  • looking very pale or feeling breathless because of a lack of red blood cells (anaemia)
  • repeated infections because of a lack of healthy white blood cells (which help fight infection)
  • bruising or bleeding easily
  • heavy, drenching night sweats
  • weight loss.

Some people have symptoms caused by high levels of IgM in the blood. The blood becomes thick and doesn’t flow freely. Doctors call this hyperviscosity. It can cause headaches or changes in vision and hearing. It may also make thinking difficult.

Sometimes people develop numbness or tingling in their hands and feet, or problems with their balance. This is due to nerve damage (neuropathy) caused by the abnormal protein in the blood.


Diagnosing WM

The most common tests used to diagnose WM are:

  • blood tests
  • a bone marrow test.

Some people have a scan to look at organs such as the lymph nodes, liver and spleen.


Staging and grading WM

Staging

Doctors use staging to assess how the lymphoma is affecting the blood and bone marrow. This helps them to know when treatment is needed and which treatment is appropriate for each person.

There is no standard system for staging WM. Instead, doctors look at several factors such as:

  • the level of red blood cells in the blood
  • the number of blood clotting cells (platelets) in the blood
  • the amount of IgM in the blood
  • the amount of a protein, called beta-2-microglobulin, in the blood.

Doctors use these factors to help them predict how the lymphoma may behave and to plan treatment.

Grading

Non-Hodgkin lymphomas are divided into two groups:

  • Low-grade (indolent) lymphomas, which usually grow slowly.
  • High-grade (aggressive) lymphomas, which grow more quickly.

WM is a low-grade lymphoma and usually develops slowly. Sometimes it can change (transform) to become a high-grade lymphoma.


Treating WM

WM often develops slowly. Some people may not need treatment straight away, or even for months or years This is called watch and wait

Even if you don’t need treatment, you will have regular check-ups at the hospital. Your specialist will examine you and do blood tests. This is to check the levels of IgM protein in your blood as well as the numbers of red blood cells, white blood cells and platelets.

Your doctor may start treatment if:

  • you have troublesome symptoms
  • the level of IgM protein in your blood is increasing
  • your blood count changes – for example, if you have low levels of red blood cells (anaemia).

The aim of treatment is to improve your quality of life and keep you well for as long as possible, with the fewest possible side effects.

The main treatments for WM are chemotherapy and a targeted therapy called rituximab. Other treatments, such as blood transfusions or plasma exchange, may be used to improve certain symptoms. You may be invited to have treatment as part of a clinical trial.

You can have most treatments for WM as an outpatient.

Chemotherapy

Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. It can be given by mouth as tablets, into a vein (intravenously) or as an injection under the skin. You may be given just one type of chemotherapy drug, or you may be given two or more chemotherapy drugs together (combination chemotherapy).

Chemotherapy is usually given in combination with a targeted therapy called rituximab.

Your specialist will explain which treatment is appropriate for you.

If you are treated with just one chemotherapy drug and rituximab, any side effects are likely to be mild. If you are having treatment with a combination of drugs, you may have more side effects. Your doctor or specialist nurse can tell you what to expect. You should always tell them about any side effects that you experience. They can give you medicines to reduce them if needed.

One of the most common side effects of chemotherapy is being more likely to get infections. Always let your doctor or nurse know if you have any signs of an infection so it can be treated straight away.

Combinations of rituximab and chemotherapy that may be used include:

• DRC – this is made up of dexamethasone (a steroid), rituximab and the chemotherapy drug cyclophosphamide

• R-bendamustine – this is made up of rituximab and the chemotherapy drug bendamustine

• FR – this is made up of the chemotherapy drug fludarabine and rituximab

FCR – this is made up of the chemotherapy drugs fludarabine and cyclophosphamide, and rituximab

• R-cladribine – this is made up of rituximab and the chemotherapy drug cladribine.

Targeted therapy

Targeted therapies are sometimes known as biological therapies. They interfere with the way cancer cells grow. These drugs only ‘target’ the cancer cells, so they have less effect on healthy cells.

Monoclonal antibodies

Rituximab is a type of targeted therapy called a monoclonal antibody. It targets proteins on the surface of B-cells. This causes the body to destroy these cells. Rituximab is given as a drip into a vein. It can be given on its own but is usually given with chemotherapy.

Cancer growth inhibitors

Cancer growth inhibitors interfere with proteins that control cell growth. This may cause the cells to die and stop the cancer from growing for a period of time.

These drugs may be used if WM comes back after treatment. Each drug may be given on its own or in combination with rituximab:

Ibrutinib (Imbruvica®) is taken as a tablet

Bortezomib (Velcade®) is given as an injection under the skin (subcutaneous injection) or as an injection into a vein.

These drugs may only be available in some situations. If a drug is not routinely available on the NHS, there may be other ways you can get access to it. Your cancer doctor can give you advice about what to do if a treatment is not available.

Steroids

Steroids are drugs that are often given with chemotherapy to treat lymphomas. They help make chemotherapy more effective. They also help you feel better and can reduce feelings of sickness.

Stem cell treatment (transplants)

This treatment is sometimes used to treat lymphoma that has come back after treatment. It is an intensive treatment, so it is not suitable for everyone.

Stem cells are a type of blood cell that can make all other types of blood cells. There are two different types of stem cell treatment:

High-dose treatment with stem cell support (autologous stem cell transplant)

Some people have treatment to put the lymphoma into remission. Then some of their own stem cells are collected from their blood and stored. Then they have high doses of chemotherapy to try to destroy any remaining lymphoma cells. After this, their stem cells are returned through a drip (like a blood transfusion). The stem cells help their blood cell numbers recover from the effects of chemotherapy.

Donor transplant (allogeneic transplant)

Some people have chemotherapy to put the lymphoma into remission and are then given stem cells from another person (a donor).

Plasma exchange

Plasma exchange (plasmapheresis) is a process that can be done to thin the blood. It may be used if your blood is thick because it contains high levels of IgM. It can take a few hours.

You lie on a bed with a small plastic tube (cannula) placed in a vein in each arm. The cannula is connected by a tube to a machine called a cell separator. Your blood is circulated through the cell separator a small amount at a time. This machine separates the plasma (which contains the IgM protein) from the blood cells. The normal blood cells, along with a plasma substitute (for the plasma that is removed), are then returned to your body through the cannula in your other arm.

Clinical trials

Your lymphoma doctor may talk to you about having treatment as part of a clinical trial. Clinical trials test new treatments or new ways of giving treatments.


Follow-up after treatment

After treatment, you will have regular check-ups. These appointments are a good opportunity for you to talk to your doctor or nurse about any concerns you have. Your doctor will want to know how you are feeling generally, and to check you are recovering from any side effects of treatment. We have more information about follow-up.


Getting support

Everyone has their own way of dealing with illness and the different emotions they experience. You may find it helpful to talk things over with family and friends or your doctor or nurse. You can also call our cancer support specialists free on 0808 808 00 00. These organisations also offer information and support:

Bloodwise offers support and information to people affected by blood cancers, including WM.

• The International Waldenstrom's Macroglobulinemia Foundation (IWMF) is an international support group for people with WM.

• The Lymphoma Association gives emotional support, advice and information on all aspects of Hodgkin lymphoma and non-Hodgkin lymphoma. It has a national network of people with lymphoma, and local groups.

Waldenström’s Macroglobulinaemia UK (WMUK) is a UK-based charity that aims to bring WM patients, carers, specialist doctors and nurses closer together, and to lobby for the latest and best treatments for WM.