This information is about a rare type of non-Hodgkin lymphoma known as Waldenström macroglobulinaemia. It may also be called lymphoplasmacytic lymphoma. It should ideally be read with our general information about non-Hodgkin lymphoma.

There are more than 20 different types of non-Hodgkin lymphoma and WM is a rare type (about one in 50 of all cases). It is more common in people over the age of 65, but it can also affect younger people. It is slightly more common in men than in women.

The lymphatic system Lymphomas are cancers of the lymphatic system. The lymphatic system is part of the body's immune system and helps us to fight infection. It is made up of lymph nodes (or lymph glands), special blood cells called lymphocytes, and organs such as the bone marrow, thymus and spleen. There is also lymphatic tissue in other parts of the body, such as the lungs, stomach and skin.

There are lymph nodes all over the body. They are connected by a network of tiny lymphatic vessels that contain a clear fluid called lymph fluid. As this fluid flows through the lymph nodes, they collect and filter out anything that the body does not need, or that could be harmful to it. This includes bacteria, viruses and damaged cells.

There are two main types of lymphocyte: B-cells and T-cells. B-cells grow and develop in the bone marrow, a spongy material that fills some of our bones and makes our blood cells.

Some B-cells develop into cells called plasma cells. Plasma cells make antibodies to help fight infections and harmful substances. Antibodies are made from a special type of protein called immunoglobulin.

WM affects B-cells when they are developing into plasma cells. These cells are called lymphoplasmacytic cells which is where the name lymphoplasmacytic lymphoma comes from.

In WM, the bone marrow produces abnormal B-cells. Although they are of no use to the body, these cells keep being made. As their numbers increase they can build up in lymph nodes and in the spleen and other organs.

These abnormal cells produce large amounts of the protein immunoglobulin macroglobulin (IgM). Macroglobulinaemia in the name Waldenström macroglobulinaemia just means there is more IgM in the blood than normal.

Large amounts of IgM in the blood can cause the blood to become thicker than normal. This is known as hyperviscosity.

The causes are unknown. Waldenström macroglobulinaemia, like other cancers, is not infectious and can't be passed on to other people.

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

Symptoms are often due to the lymphoma cells filling up the bone marrow so that it cannot produce enough normal blood cells.

The most common symptoms are:

• feeling weak and tired, and looking pale due to a lack of red blood cells (anaemia)
• bruising or bleeding more easily due to a low number of platelets (cells which help the blood to clot) in the blood
• repeated infections because the number of white cells (which help fight infection) in the blood is low
• weight loss.

If there are high levels of the IgM protein in the blood, some people may have symptoms caused by the blood becoming too thick and not flowing freely (hyperviscosity). Problems can include changes in vision, headaches, hearing loss, or confusion.

Sometimes people develop numbness or tingling in their hands or feet. This is due to damage to nerves caused by the abnormal protein in the blood.

All these symptoms can be caused by other conditions as well as Waldenström macroglobulinaemia. But they should always be checked out by a doctor.

Your GP will examine you and do a blood test. Depending on the result, you may then be referred to a hospital for specialist advice or treatment. The doctor at the hospital will ask you about your symptoms and any other health problems you have, examine you physically, and do further blood tests. These tests will show if there are abnormal cells in the blood and will also measure the amount of the IgM protein in your blood. The doctor may also ask you to have further tests, such as a bone marrow test, and a CT scan.

Bone marrow sample

Your specialist may want to take a sample of marrow (biopsy) to examine under a microscope.

The sample is usually taken from the back of your hip bone (pelvis). You will be given an injection of local anaesthetic to numb the area. The doctor will then pass a needle through the skin into the bone and draw a small sample of liquid marrow into a syringe (bone marrow aspirate). After this, the doctor will take a small core of marrow from the bone (a trephine biopsy). Both samples will be looked at later under the microscope.

The test can be done on the ward or in the outpatients department. The whole procedure takes about 15-20 minutes. It may be uncomfortable as the marrow is drawn into the syringe but this should only last for a few seconds.

You may feel bruised and have an ache for a few days after the test. This can be eased with mild painkillers.

CT scan

A CT scan is a special type of x-ray. It is used to find out if WM has affected lymph nodes or organs such as the liver.

A number of pictures are taken from different angles, and fed into a computer which shows detailed pictures of the inside of the body. This involves lying still for 45–60 minutes.

You may be asked not to eat or drink anything for at least four hours before your appointment. Most people who have a CT scan are given a drink or injection into a vein in the arm about an hour before the scan, to allow particular areas to be seen more clearly. For a few minutes, this may make you feel hot all over. Before having the injection or drink it is important to tell your doctor or the person doing the test if you are allergic to iodine or have asthma.

Waldenström macroglobulinaemia often develops slowly. This means that some people may not need treatment straight away. Even if you don't need treatment, you will still have regular check ups at the hospital. Your specialist will examine you and do blood tests to check the levels of your red blood cells, white blood cells and platelets (a full blood count of FBC) and the levels of IgM protein in your blood.

Your doctor will consider starting treatment if:

• you begin to get symptoms
• the level of IgM protein in your blood is increasing
• something in your blood count changes, such as developing low levels of red blood cells (anaemia).

The main treatment for WM is chemotherapy (anti-cancer) drugs. Some symptoms can also be improved with plasma exchange (see below) and blood transfusions.

Chemotherapy

Chemotherapy is the use of anti-cancer (cytotoxic) drugs. It works by killing abnormal B-cells when they are dividing to make more copies of themselves. This controls the disease and reduces symptoms.

Chemotherapy may be given as several sessions of treatment over a specific length of time. Usually there is more than one type of chemotherapy that may be helpful. Your doctor will discuss the different options with you. You may be asked to have your chemotherapy as part of a research trial.

Your doctor will give you advice about how to cope with any side effects you have from the treatment, and can give medicines to reduce them if necessary.

Chlorambucil (Leukeran®) is taken as a tablet and is usually given daily for the time recommended by your specialist. It should be kept in the fridge.

Side effects are usually mild. One of the common side effects is a temporary reduction in blood cell production. This can result in anaemia, risk of bruising or bleeding, and infection. Any infection will need to be treated with antibiotics, and your blood count will be monitored throughout your treatment. If your temperature goes up, or you suddenly feel unwell, even with a normal temperature, contact your hospital or doctor straight away.

You may have some mild nausea and vomiting but this can usually be well controlled with anti-sickness drugs. Other possible side effects include a loss of appetite, mouth ulcers, a skin rash or diarrhoea.

Fludarabine is usually taken as tablets but it may be given as an intravenous injection (an injection into a vein). It is taken every day for five days. The treatment is usually repeated every three to four weeks.

Common side effects include an increased risk of infection. The first sign of infection may be a high temperature or feeling cold and shivery. Any infection needs to be treated immediately with antibiotics. Again, if you have a high temperature, contact your hospital or doctor straight away. You may have some mild nausea and vomiting, but this is usually well controlled with anti-sickness drugs. Other possible side effects include loss of appetite, mouth ulcers, diarrhoea and sometimes constipation.

Other drugs, such as cyclophosphamide, and combinations of drugs (for example the CHOP regimen – cyclophosphamide, doxorubicin, vincristine and prednisolone) may be used in particular circumstances.

Plasma exchange

Plasma exchange (or plasmapheresis) is a process carried out to ‘thin’ the blood if high levels of IgM are making it thick. The procedure can take 2-4 hours and is not painful.

You will lie on a bed with a drip placed in each arm. The drip is connected to a machine (called a cell separator), which your blood is circulated through, 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 drip in your other arm.

The number of plasma exchanges you have will depend on the amount of the IgM protein in your blood, your symptoms and response to treatment, such as chemotherapy.

Plasma exchange may be done once a month if it is the only treatment being given. If there are extremely high levels of IgM protein in the blood it can be done as an emergency treatment (daily for three days) before chemotherapy starts.

Surgery

Some people who have an enlarged spleen find that removing the spleen and having chemotherapy helps to relieve symptoms. Your doctor will discuss the operation with you.

After you have had your spleen removed, you may be more prone to certain infections. In order to prevent this, various vaccinations and antibiotics will be prescribed for you. Your doctor will tell you how long you will have to take antibiotics. It may be for several years or it may be for life.

Monoclonal antibody therapy

A monoclonal antibody called rituximab (also known as Mabthera®) is sometimes used to treat WM. It is given as a drip into a vein (intravenous infusion). Monoclonal antibodies are drugs that recognise, target, and stick to particular proteins on the surface of cancer cells. They can stimulate the body’s immune system to destroy these cells.

Rituximab may be given on its own or along with chemotherapy.

Once your course of treatment has finished, you will continue to have regular blood tests and check-ups. If you feel unwell at any time between these appointments, it is important to let your doctor know as soon as possible.

Research into WM is going on all the time. It gives doctors more understanding about the disease and helps them to improve treatment.

Cancer doctors use clinical trials to assess new treatments. Before any trial is allowed to take place, it must have been approved by an ethics committee, which checks that the trial is in the interest of patients.

Your doctor must discuss the treatment with you so that you have a full understanding of the trial and what it involves. You may decide not to take part, or to withdraw from a trial, at any stage. You will then receive the best standard treatment available.

You may have many different emotions, including anxiety and fear. These are normal reactions and are part of the process many people go through in trying to come to terms with their condition.

Everybody has their own way of coping with difficult situations. Some people find it helpful to talk to friends or family, while others prefer to seek help from people outside their situation. Some people prefer to keep their feelings to themselves. There is no right or wrong way to cope, but help is available if you need it.

This section has been compiled using information from a number of reliable sources, including:

• Oxford Textbook of Oncology (2nd edition). Eds Souhami et al. Oxford University Press, 2002.
• Wintrobe’s Clinical Haematology (11th edition). Eds Lee et al. Williams and Wilkins, 2004.
• Improving Outcomes in Haemato-Oncology. National Institute of Clinical Excellence, November 2003.
• Guidelines on the Management of Waldenström Macroglobulinaemia. British Society of Haematology, 2006.

For further references, please see the general bibliography.