Waldenström macroglobulinaemia (also known as lymphoplasmacytic lymphoma)
Waldenström macroglobulinaemia (WM) is a rare type of non-Hodgkin lymphoma. It’s also known as lymphoplasmacytic lymphoma. This information should ideally be read with our section on non-Hodgkin lymphoma.
Non-Hodgkin lymphoma and WM
Back to top
WM is 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’simmune 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 are lymph nodes all over the body. As lymph fluid flows through the lymph nodes, the nodes collect and filter out anything that is harmful or that the body doesn't need. This includes bacteria, viruses, damaged cells and cancer cells.
Lymph fluid contains white blood cells called lymphocytes. Blood cells are made in the bone marrow. Millions of new ones are made every day to replace old and worn-out blood cells. Once new blood cells have matured, they are released into the bloodstream to do different jobs. The job of white blood cells and lymphocytes is to fight infection.
The two main types of lymphocytes are B-cells and T-cells. 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 (LPL) cells, which is where the name lymphoplasmacytic lymphoma comes from.
In WM, the bone marrow produces abnormal LPL cells. Although they are of no use to the body, these cells keep being made. As their numbers increase, they build up in the bone marrow. The bone marrow becomes overcrowded with LPL cells and can’t make enough healthy blood cells. LPL cells can also build up in lymph nodes, the spleen and other organs causing them to swell.
These abnormal LPL cells produce large amounts of the protein immunoglobulin macroglobulin (IgM). Macroglobulinaemia (the M in WM) 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 and risk factors for WM
Back to top
The causes of WM are unknown. People who have a family member with lymphoma have a higher than average risk of developing WM. But because WM is rare, their overall risk of getting it remains very low. Most people who develop WM don’t have any family members with lymphoma. Like other cancers, it’s not infectious and can’t be passed on to other people.
People who have a condition called MGUS in which there is some abnormal IgM in their blood sometimes develop WM. We have more information on MGUS.
Signs and symptoms of WM
Back to top
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.
When symptoms develop, they are usually caused by lymphoma cells overcrowding the bone marrow. This means that it can’t make enough normal healthy blood cells.
The most common symptoms are:
feeling weak and tired (fatigue)
looking very pale due to a lack of red blood cells (anaemia)
bruising or bleeding more easily caused by too few platelets (cells that help the blood to clot)
repeated infections because of a lack of healthy white blood cells (which help fight infection)
heavy, drenching, night sweats
Some people may have symptoms caused by high levels of the IgM protein in the blood. The blood becomes too thick and doesn’t flow freely (hyperviscosity). This can cause changes in your 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 you should always tell your doctor if you have any symptoms.
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 biopsy and a CT scan.
Bone marrow biopsy
This test may be done to check for WM cells in the bone marrow and to check how well the bone marrow is working.
A doctor or nurse takes a small sample of bone marrow from the back of your hip bone (pelvis). Before the bone marrow sample is taken, you’ll be given a local anaesthetic injection to numb the area. You may also be offered a short-acting sedative to reduce any pain or discomfort during the test.
You’ll be asked to lie on your side. The doctor or nurse 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). It can feel uncomfortable for a few seconds when the liquid marrow is drawn into the syringe. After this, they will take a small core of marrow from the bone (a trephine biopsy). A small plaster or dressing will then be placed over the skin.
The samples are sent to the laboratory for testing. It can take 7-10 days to get the results of a bone marrow biopsy.
You may feel bruised after having a sample of bone marrow taken, and have an ache for a few days. This can be eased with mild painkillers.
CT (computerised tomography) scan
A CT scan takes a series of x-rays, which build up a three-dimensional picture of the inside of the body. It is used to find out if WM has affected your lymph nodes, or organs such as the liver or spleen. The scan takes 10-30 minutes and is painless. It uses a small amount of radiation, which is very unlikely to harm you and will not harm anyone you come into contact with. You will be asked not to eat or drink for at least four hours before the scan.
You may be given a drink or injection of a dye, which allows particular areas to be seen more clearly. This may make you feel hot all over for a few minutes. It’s important to let your doctor know if you are allergic to iodine or have asthma, because you could have a more serious reaction to the injection.
Our general information about non-Hodgkin lymphoma explains these tests in more detail.
WM often develops slowly. It is sometimes described as an indolent lymphoma. 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. This is to check the levels of your red blood cells, white blood cells and platelets (a full blood count or FBC).They will also check the levels of IgM protein in your blood.
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 develop 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 targeted therapies or steroid treatment. Other treatments such as blood transfusions or plasma exchange may also be used to improve particular symptoms. You may be invited to have treatment as part of a clinical trial.
Most treatments for WM can be given as an outpatient.
Chemotherapy is the use of 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 also often 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, 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:
Combinations of chemotherapy drugs used include:
DRC - dexamethasone (a steroid), rituximab and cyclophosphamide
CHOP - cyclophosphamide, vincristine, doxorubicin and prednisolone (a steroid)
FCR - fludarabine, cyclophosphamide and rituximab.
Steroids are substances that are naturally produced in the body but that can be made synthetically as drugs. They control many different functions in the body such as regulating our immune system. Steroids may be used to help destroy the abnormal LPL cells and make chemotherapy more effective. They're usually given as tablets, but may also be given as an injection into a vein (intravenously).
Possible side effects of steroids include weight gain, restlessness, agitation and sleep disturbance. These are temporary and usually go away when treatment finishes.
Rituximab (Mabthera ®) is a type of targeted therapy called a monoclonal antibody. These 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 is given as a drip into a vein (infusion). It may be given with chemotherapy and/or steroids.
Bortezomib (Velcade ®) is a cancer growth inhibitor. It works by interfering with a group of enzymes that control cell growth. This may cause the cells to die and stop the cancer from growing. Bortezomib may be given on its own or in combination with chemotherapy, rituximab or steroids. It is given as an injection under the skin (subcutaneous injection) or as an injection into a vein.
Stem cell transplants
Some people with WM may have treatment using stem cells. Stem cells are blood cells at their earliest stage of development. All blood cells develop from stem cells.
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.
Stem cell transplants are specialised and complex treatments. There are many side effects and complications. Stem cell transplants are not suitable for everyone. Your doctor will take into account your age and general health before advising you to have one.
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 abnormal IgM are making it thick. The procedure can take a few hours and is not painful.
You will lie on a bed with a plastic tube (cannula) placed 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 drip in your other arm.
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 current treatment.
Your doctor must discuss the treatment with you, and have your informed consent before entering you into a trial. You may decide not to take part or to withdraw from the trial at any stage. You will then receive the best current 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 totalk 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.
The International Waldenström’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 non-Hodgkin lymphoma. It has a national network of people with lymphoma and local groups.
Leukaemia & Lymphoma Research provides written information on WM.
This section has been compiled using information from a number of reliable sources, including:
Owen R, et al. Guidelines on diagnosis and management of Waldenström’s Macroglobulinaemia. British Journal of Haematology. 2014.
Buske C, et al. Waldenström’s macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2013. European Society for Medical Oncology (ESMO).
Greer, et al. Wintrobe’s Clinical Hematology. 12th edition. 2009. Lippincott Williams and Wilkins.
With thanks to Dr Shirley D'Sa, Consultant Haematologist, and the people affected by cancer who reviewed this edition.
Thank you to all of the people affected by cancer who reviewed what you're reading and have helped our information to grow.
You could help us too when you join our Cancer Voices Network - find out more.