Waldenström macroglobulinaemia (also known as lymphoplasmacytic lymphoma)
Waldenström macroglobulinaemia is a rare type of non-Hodgkin lymphoma. It is also known as lymphoplasmacytic lymphoma. It's more common in people over 65, but it can also affect younger people. It is slightly more common in men than in women.
Non-Hodgkin lymphoma is a cancer of the lymphatic system. The lymphatic system is part of the body’s immune system and helps us fight infection. It's made up of organs such as the bone marrow, thymus, spleen, and the lymph nodes (or lymph glands). Lymph nodes are connected by a network of tiny lymphatic vessels that contain lymph fluid. There is also lymphatic tissue in other organs, such as the skin, lungs and stomach.
There are lymph nodes all over the body. As lymph fluid flows through the lymph nodes, the nodes collect and filter out anything harmful or anything that the body doesn't need. This includes bacteria, viruses, damaged cells and cancer cells.
Lymph fluid contains cells called lymphocytes. These are a type of white blood cell that help the body fight infection and disease.
Lymphocytes start to grow in the bone marrow, where blood cells are made. The two main types of lymphocytes are B-cells and T-cells.
B-cells mature in the bone marrow, while T-cells mature in the thymus gland behind the breast bone. When they're mature, both B-cells and T-cells help to fight infections.
Lymphoma is a disease where either T-cells or B-cells grow in an uncontrolled way.
Some B-cells develop into cells called plasma cells. Plasma cells make antibodies to help fight infections. Antibodies are made from a special type of protein called immunoglobulin.
WM affects B-cells when they are developing into plasma cells. These developing 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, the spleen and other organs.
These abnormal B-cells produce large amounts of the protein immunoglobulin macroglobulin (IgM). Macroglobulinaemia (the M in WM) just means there is more lgM in the blood than normal.
Large amounts of IgM in the blood can cause it to become thicker than normal. This is known as hyperviscosity.
Causes of Waldenström macroglobulinaemia
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The causes of WM are unknown. Like other cancers, it’s not infectious and cannot be passed on to other people.
Signs and symptoms of Waldenström macroglobulinaemia
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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.
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 (fatigue), 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 that help the blood to clot) in the blood
repeated infections because the number of white blood cells (which help fight infection) in the blood is low
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). These symptoms can include changes in vision, headaches, hearing loss, or confusion. 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.
These symptoms can also be caused by other conditions, but they should always be checked out by a doctor.
How Waldenström macroglobulinaemia is diagnosed
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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. They will 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 bone 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, they will take a small core of marrow from the bone (a trephine biopsy). Both samples will then be looked at under a 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.
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 an injection into a vein in the arm, about an hour before the scan. This allows particular areas of the inside of the body to be seen more clearly. It may make you feel hot all over for a few minutes.
Before having the injection or drink it is important to tell your doctor and the person doing the test if you are allergic to iodine or have asthma.
Treatment for Waldenström macroglobulinaemia
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WM often develops slowly. This means that some people may not need treatment straight away, or even for months or years.
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 to check the levels of your red blood cells, white blood cells and platelets (a full blood count or 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
your blood count changes, such as developing low levels of red blood cells (anaemia).
The main treatment for WM is chemotherapy. It may be given on its own or in combination with other treatments such as a monoclonal antibody treatment or steroid treatment. Other treatments such as blood transfusions or plasma exchange may also be used to improve particular symptoms.
Chemotherapy is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells. It can be given as tablets or into a vein (intravenously). You may be given just one type of chemotherapy drug or you may be given two or more chemotherapy drugs together (combination chemotherapy). Your specialist will explain which treatment is appropriate for you.
If you are treated with just one chemotherapy drug, any side effects are likely to be mild. If you’re 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 you have. They can give you medicines to reduce them if necessary.
One of the most common side effects of chemotherapy is being more prone to infections. Always let your doctor or nurse know if you have any signs of an infection so it can be treated straight away.
The chemotherapy drugs most commonly used to treat WM are listed below.
Chlorambucil (Leukeran ®)
Chlorambucil is taken as a tablet and is usually given daily for the time recommended by your specialist. It should be kept in the fridge.
Fludarabine (Fludara ®)
Fludarabine usually taken as tablets, but it may be given as a ‘drip’ into a vein (intravenous infusion).
Cladribine (Leustat ®)
Cladribine is a similar type of drug to fludarabine. It may be given as a ‘drip’ into a vein (intravenous infusion) or as an injection just under the skin (subcutaneous injection).
Cyclophosphamide may be taken as tablets or given into a vein (intravenously).
Bendamustine (Levact ®)
Bendamustine is a newer treatment for WM. It is given as a ‘drip’ into a vein.
Combinations of chemotherapy drugs are sometimes given such as the CHOP regimen, which is made up of cyclophsphamide, vincristine, doxorubicin and the steroid prednisolone.
Steroids can be used as part of your treatment to help destroy the abnormal B-cells and make chemotherapy more effective. They're usually given as tablets, but may also be given as an injection into a vein (intravenous).
The side effects of steroids are temporary and usually go away when treatment finishes.
Monoclonal antibody therapy
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.
A monoclonal antibody called rituximab (Mabthera ®) is sometimes used to treat WM. It's given as a drip into a vein (infusion). Rituximab may be given with chemotherapy and/or steroids.
Bortezomib (Velcade ®)
Bortezomib is a newer type of treatment and may be given on its own or in combination with steroids and/or rituximab. It may be given into a vein or as an injection under the skin (subcutaneous injection). It may be given 1-2 times a week, every 3-5 weeks. The main side effects of bortezomib are tingling, numbness or pain in the hands and feet.
Stem cell transplants
Some people with WM may have treatment involving the use of their own stem cells or stem cells from a donor. Stem cells are a special type of blood cell that can make all other types of blood cells.
There are serious side effects associated with these treatments. They’re not suitable for everyone and aren’t done routinely. Doctors take into account a person's general health and fitness before recommending them.
Some people have some of their own stem cells collected and stored. This allows them to have higher doses of chemotherapy to destroy the lymphoma cells.
After the chemotherapy, their stem cells are returned by a drip (like a blood transfusion) to help their blood cells recover from the effects of chemotherapy. This is called high-dose chemotherapy with stem cell support.
Some people may have treatment using stem cells from another person (a donor). This is called a donor (allogeneic) transplant.
David talks about his experience of having a stem cell transplant.
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 plastic tube (cannula) placed in each arm. The cannula 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 IgM protein in your blood, your symptoms and your 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 1–2 days) before chemotherapy starts.
Rarely, people who have an enlarged spleen (due to a build-up of abnormal B-cells) may have it removed with surgery. Removing the spleen before chemotherapy starts may help to relieve symptoms in some people. Your doctor will discuss the operation with you.
After you have had your spleen removed, you may be more prone to certain infections. To prevent this, your doctor will prescribe different vaccinations and antibiotics for you. They will tell you how long you will have to take antibiotics for – it may be for several years or for life.
New treatments for WM are being researched all the time. Your doctor may invite you to take part in a clinical trial to compare a new treatment against the best available standard treatment.
Your doctor must discuss the treatment with you, and have your informed consent before entering you into a trial.
Before any trial is allowed to take place, it must be approved by a research ethics committee, which protects the interests of those taking part. You may decide not to take part or to withdraw from the trial at any stage. You will then receive the best standard treatment available.
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.
Everyone has their own way of dealing with their 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 contact our cancer support specialists, or the organisations listed below, for more information and support.
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.
WM UK Support Group
WM UK Support Group offers support for people in the UK and Eire with WM, as well as to their family and friends. Have an online forum, help line and email.
International Waldenström’s Macroglobulinaemia Foundation
The IWMF is an international support group for people with WM.
The Lymphoma Association
Lymphoma Association gives emotional support, advice and information on all aspects of non-Hodgkin lymphoma. Has a national network of people with lymphoma and local groups.
Leukaemia CARE is a national group that promotes the welfare of people with leukaemia and other blood disorders, including non-Hodgkin lymphoma. Has regional support groups in many counties.
Leukaemia & Lymphoma Research
Leukaemia & Lymphoma Research provides written information on WM.
This section has been compiled using information from a number of reliable sources, including:
Guidelines on the Management of Waldenström Macroglobulinaemia. 2006. British Society of Haematology.
Lee, et al. Wintrobe’s Clinical Hematology. 12th edition. 2009. Lippincott Williams and Wilkins.
Best Practice in Lymphoma Diagnosis and Reporting, Specific disease appendix. Parker A, et al BSCH guidelines. 2010.
Facilities for the treatment of adults with haematological malignancies - 'Levels of Care' British Committee for Standards in Haematology. 2010.
Thanks to Dr Shirley D'Sa, Consultant Haematologist, and all of the people affected by cancer who reviewed this edition.
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