Waldenström’s macroglobulinaemia: symptoms, diagnosis and treatment

Waldenström’s macroglobulinaemia, usually abbreviated to WM, is a rare cancer of the white blood cells. Macmillan Cancer Support explains that it develops when lymphoplasmacytic cells, which are a type of B-cell, become abnormal. B-cells are white blood cells that normally help fight infection. The abnormal cells usually build up in the bone marrow, lymph nodes, spleen and other organs.

As the abnormal cells accumulate they make large amounts of a protein called immunoglobulin M, or IgM. Doctors may also call this the M-protein, M-band or paraprotein. IgM circulates in the blood, and Macmillan explains that large amounts can make the blood thicker and more slow-moving. This one feature explains why WM can cause both low blood counts and symptoms related to thick blood.

WMUK, the UK charity for WM and lymphoplasmacytic lymphoma, makes the point that WM is a cancer of the white blood cells and that crowding out of healthy blood cells in the bone marrow leads to fatigue, repeated infections and easy bruising or bleeding.

Macmillan says WM usually develops over a long period of time and some people have no symptoms. When symptoms occur, they fall into two groups: those caused by lymphoma cells crowding the bone marrow, and those caused by excess IgM.

None of these symptoms is specific to WM, and most people with fatigue, infections or tingling have a more common explanation. WMUK advises mentioning all symptoms, however mild, to your healthcare team, and notes that symptoms may be caused by WM, by WM-related conditions, or by treatment side effects, so it is important to discuss all of them.

See a GP if you have persistent tiredness, unexplained weight loss, drenching night sweats, repeated infections or unusual bruising. Sudden severe headache, confusion, a nosebleed that will not stop or sudden changes in vision need urgent assessment through NHS 111, A&E or 999, as appropriate, because they can have many serious causes. People already diagnosed with WM should follow the advice given by their haematology team on whom to contact urgently.

Macmillan says the causes of WM are mostly unknown, though some things may increase the risk. WM is sometimes linked with monoclonal gammopathy of unknown significance (MGUS) of the IgM type, a condition in which abnormal IgM is present in the blood. People with a family member with lymphoma have a higher than average risk, but because WM is rare their risk remains very low, and most people with WM have no relatives with lymphoma.

Like other cancers, WM is not infectious and cannot be passed on to other people.

The most common tests for diagnosing WM, according to Macmillan, are blood tests and bone marrow tests. Blood tests measure blood counts and the level of IgM. A bone marrow biopsy looks at the cells directly, and blood or bone marrow samples can be used to look at the genes in the lymphoma cells. Macmillan says around 9 out of 10 people with WM have a genetic change called MYD88. Scans can be used to look at organs such as the liver and spleen and to show lymph nodes, and an enlarged lymph node may be biopsied.

There is no standard staging system for WM. Instead, doctors look at several factors such as the level of red blood cells, the number of platelets, the amount of IgM and the amount of a protein called beta-2-microglobulin to help predict how the lymphoma may behave and to plan treatment. In the NHS, a team of specialists called a multidisciplinary team (MDT) meets to discuss the best treatment for each person.

Because WM often develops slowly, Macmillan says some people do not need treatment straight away, or even for months or years. Even so, regular hospital check-ups include examination and blood tests of IgM, red cells, white cells and platelets. Macmillan lists the triggers for starting treatment as troublesome symptoms, a rising IgM level and changes in blood count such as anaemia. WMUK adds that doctors take into account your age, general health and fitness and what treatment you have had before.

The aim, in Macmillan’s words, is to improve quality of life and keep you well for as long as possible with the fewest possible side effects. WMUK is explicit that there is no cure, and that the aim is remission, which can last for years.

• Chemotherapy combined with rituximab, a monoclonal antibody: both charities name DRC (dexamethasone, rituximab and cyclophosphamide) and bendamustine with rituximab as common combinations.

• Targeted treatments: WMUK names BTK inhibitors such as zanubrutinib and ibrutinib; Macmillan notes ibrutinib and bortezomib may be used if WM comes back, and that some drugs may only be available in some situations on the NHS.

• Steroids, which are often given with chemotherapy to make it more effective.

• Stem cell transplant, which WMUK describes as intensive and only offered as second- or third-line treatment.

• Treatment of symptoms: blood transfusions for symptoms of anaemia, and plasma exchange to thin the blood.

• CAR T-cell therapy: WMUK says it is not currently offered for WM but is likely to appear in clinical trials.

WMUK says that when treatment finishes most people go into remission, which may last for years, and that the team will monitor IgM levels. If levels rise and symptoms worsen, further treatment may be discussed. Courses are described as first-line, second-line and third-line.

Practical support comes from a clinical nurse specialist, the haematology team, and charities including WMUK, Lymphoma Action and Blood Cancer UK, all named in the sources. Macmillan says some treatments are available as outpatient care. Some people also choose a private haematology consultation for a second opinion or quicker clinic access, while treatment itself is usually delivered by the NHS team that knows your history.