What Is Waldenström Macroglobulinaemia?

  • Adeline Rankin Postgraduate certificate in clinical education, Clinical education, University of East Anglia, UK
  • Ellen Rogers MSc in Advanced Biological Sciences, University of Exeter, UK

Waldenström macroglobulinaemia (WM), also known as lymphoplasmacytic lymphoma, is a rare type of cancer that affects a type of immune cell called B cells (or B lymphocytes). Specifically, WM affects a subset of the B cells known as the plasma cells, which produce antibodies (or immunoglobulins) - proteins that recognise and protect you from microorganisms and other unwanted invaders. There are five types of immunoglobulins: IgA, IgD, IgE, IgD, and IgM, which have different roles in fighting infection. If you have WM, your plasma cells become abnormal and produce large quantities of IgM and/or IgG. These excess antibodies can make the blood thick and slow-flowing and increase your risk of developing blood clots. They may also cause you to experience fatigue or anaemia, which are the most common symptoms of WM. Following the appearance of these symptoms, WM is usually diagnosed via blood testing, which reveals the high levels of IgM and/or IgG in the blood.¹

Who is affected by waldernström’s macroglobulinaemia?

WM is a very rare disease, with only around 350 people being diagnosed with the condition in the UK each year.¹ WM is more common in men than women and predominantly affects older patients, with the average patient being diagnosed at 71 years of age.²,³ White Europeans are at an increased risk of WM compared to other ethnic groups, as are individuals who have a relative who has suffered from the condition previously.³ 

How does waldenström's macroglobulinemia develop?

In a healthy immune system, B cells produce antibodies that help the body identify and fight off infections from viruses, bacteria, and parasites. Inactive B cells regularly circulate in the blood until they find and bind to an antigen - a protein, carbohydrate, or other molecule found on the surface of disease-causing microorganisms. Once activated, B cells differentiate into plasma cells, which begin producing specific antibodies to help fight the infection. Even when the invading microorganisms have been killed, these plasma cells remain in your blood in case you are exposed to the same antigen again in the future.⁴ This phenomenon is known as “immunological memory”. 

In WM, the gene for the plasma cell protein “Myeloid Differentiation Factor 88” (MYD88) becomes mutated. The mutation is called a ‘gain of function’ mutation as it causes cells to bypass the body’s “quality control” checks and replicate uncontrollably. These rapidly dividing cells are called malignant cells.⁵ These malignant plasma cells (or lymphoplasmacytic cells) produce non-functional IgM proteins which accumulate in the blood but cannot fight infection. As WM develops and worsens, the lymphoplasmacytic cells may begin to accumulate in some organs, such as the spleen and lymph nodes or the bone marrow.

Bone marrow infiltration

The bone marrow is soft tissue found within the bones. It contains stem cells, which are able to develop into many different types of blood cells, including red blood cells (which carry oxygen around the body), white blood cells (which are responsible for fighting infection), and platelets (which are needed for blood clotting).⁶ When lymphoplasmacytic cells infiltrate and accumulate within the bone marrow, the normal development of blood cells becomes disrupted. This can impact your health in several ways: a lack of red blood cells can cause anaemia; a lack of white blood cells can increase your risk of infection; and a low platelet count can increase your risk of bleeding and excessive blood loss. 

Spleen and lymph node infiltration

Whilst the white blood cells are “born” in the bone marrow, they develop and mature in the spleen and lymph nodes. If the lymphoplasmacytic cells produced in WM collect in the spleen or lymph nodes, they can become enlarged. If your doctor suspects you have WM, they may examine your lymph nodes to see if they are swollen. 

Symptoms of waldenström’s macroglobulinaemia 

Many WM patients are asymptomatic (have/experience no visible symptoms). However, known symptoms of WM include:

  • Fatigue and breathlessness: These are often the first symptoms of WM to emerge and are secondary to anaemia caused by the disruption of normal red blood cell development.
  • Fever 
  • Weight loss
  • Enlarged lymph nodes, which feel like lumps in the neck or groin. 
  • An enlarged spleen: if the spleen becomes enlarged, it may exert pressure on your stomach, causing you to feel full quickly.⁵

WM is often preceded by a condition known as Monoclonal Gammopathy of unknown significance (MGUS). MGUS is often identified and diagnosed when routine blood tests show a high level of immunoglobulins in your blood, indicating that your B cells have become abnormal. While MGUS itself does not require any treatment, it does increase your risk of developing B cell cancer (such as WM) in the future. 

How is waldernström’s macroglobulinaemia diagnosed?

Blood tests

As WM is often asymptomatic, the first indicator of WM is usually abnormal blood test results, which may reveal you have anaemia or high levels of immunoglobulin in the blood. Further tests, such as immunoglobulin electrophoresis and immunofixation, can be carried out to further investigate these findings and determine the type(s) of immunoglobulin present in your blood. As above, WM is associated with high levels of IgM antibodies.¹ 

Bone marrow biopsy

To determine whether abnormal blood test results are due to WM, your doctor may take a small sample of your bone marrow and look at it under a microscope. A bone marrow biopsy is performed by using a needle to take a sample of the bone marrow - usually from the hip. The procedure is performed under local anaesthetic, but a sedative may be given to help you relax during the procedure.⁷ The biopsied bone marrow is then examined under a microscope to look at the types of cells within the sample and to see whether lymphoplasmacytic cells are present. 

Eye examination

The high levels of IgM in the blood of WM patients can cause the blood vessels in the back of the eye to swell and become leaky. Your doctor may use an ophthalmoscope or retinal photograph to examine your eye and look for these changes.

Computed tomography (CT) scans

If your doctor suspects you have WM, they will submit you for a CT scan to look for swelling in your spleen, liver, and lymph nodes. This helps to determine how advanced your cancer is and helps your medical team decide on the most appropriate treatment for you.¹

How is waldernström’s macroglobulinaemia treated?

Your treatment for WM will depend on your symptoms and test results. If you are asymptomatic (not experiencing any symptoms), your doctor may choose to take a ‘watch and wait’ approach. As such, you will not need any treatment but will be closely monitored and undergo regular blood tests.

If your condition is causing troublesome symptoms (such as anaemia, weakened immunity or poor blood clotting), your doctor will likely suggest you start treatment. This may include:

  • Chemotherapy: drugs that kill or stop lymphoplasmacytic cells from dividing. There are a number of different combinations of chemotherapy which can be used for WM, and these are tailored to each patient depending on the severity of their condition, their symptoms, and any complications they may be experiencing.¹
  • Immunotherapy: immunotherapy uses antibodies that have been specially designed in a laboratory to target cells with specific proteins on their surface. The lymphoplasmacytic cells present in WM display a protein called CD20 on their surface, which acts as the target. Rituximab is a drug that contains antibodies that bind to CD20 on the surface of these cells. This binding activates your immune system, which goes on to react against and kill the cancerous cells.
  • Stem cell transplants: stem cell transplantation is not a common treatment but is occasionally used in younger patients with aggressive WM. Stem cells have the potential to develop into any type of blood cell and can be used to replace diseased (or cancerous) blood cells within the body. A stem cell transplant involves using chemotherapy to kill the diseased lymphoplasmacytic cells and then replacing them with stem cells or healthy B cells collected from the patient or a stem-cell donor.⁸ 
  • Splenectomy: although very rare, some WM patients will suffer from significantly enlarged spleens, which can cause severe discomfort. In these cases, the decision may be taken to remove the spleen in surgery.

Other complications associated with waldernströom’s macroglobulinaemia

The abnormal antibodies produced by the cancerous cells found in WM can result in some complications, which are described below.

Hyperviscosity syndrome

The high levels of IgM antibodies produced by cancerous B cells may cause patients to develop a condition called Hyperviscosity Syndrome. Hyperviscosity syndrome causes the blood to become thicker and disrupts its normal flow through smaller blood vessels. This can lead to headaches, blurred vision, and neurological symptoms like confusion, peripheral neuropathy (numbness, tingling, or pain in the hands and feet), and strokes. Hyperviscosity syndrome may also put extra pressure on the heart and, in severe cases, cause heart failure. Despite their thickened blood, patients with hyperviscosity syndrome are prone to spontaneous bleeding, often from the nose, mouth or inside the gastrointestinal tract. 

Hyperviscosity syndrome is a medical emergency and may need a treatment called plasma exchange. Plasma exchange involves passing your blood through a machine which separates the red blood cells, white blood cells, and platelets from the liquid plasma containing the abnormal IgM antibodies. The healthy blood cells are then replenished with healthy plasma and returned to the body.


High levels of a type of IgM antibody called cryoglobulins in the blood can cause the blood to thicken to a gel-like consistency in cold temperatures, significantly reducing circulation to the face, hands, and feet.⁹ 

Cold agglutinin disease

Cold agglutinin disease occurs when abnormal IgM molecules called cold agglutinins bind to your red blood cells, causing them to be destroyed when you enter cold environments or otherwise become cold. Cold agglutinin disease may cause painful bluish-purple discolouration on the extremities (e.g. the hands and feet) when out in the cold, as well as anaemia as more red blood cells are destroyed.¹⁰ If you become anaemic due to cold agglutinin disease (or WM alone), you may require regular blood transfusions to keep your red blood cell count high.


Waldenström’s macroglobulinaemia is a rare cancer of the white blood cells that mainly affects people over the age of 70. Being diagnosed with any form of cancer is scary, and every patient will have different needs and require different types of treatment and support. You do not have to go through this journey alone. In the UK, there are many organisations that are able to offer you more information about your diagnosis and treatment plan and can help support you and your family. These include Macmillan, Waldenstrom’s Macroglobulinaemia UK, and Cancer Research UK. A very useful information leaflet produced by the Leukaemia and Lymphoma Society can be found here


  1. Macmillan Cancer Support. About Waldenström’s macroglobulinaemia [Internet]. Accessed Sept 30 2023 via https://www.macmillan.org.uk/cancer-information-and-support/lymphoma/non-hodgkin/types/waldenstroms-macroglobulinaemia 
  2. Gertz MA. Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management. American J Hematol. 2021;96:258–69. 
  3. Dimopoulos MA, Kastritis E. How I treat Waldenström macroglobulinemia. Blood. 2019;134:2022–35. 
  4. Allen HC, Sharma P. Histology, Plasma Cells. StatPearls, Treasure Island (FL): StatPearls Publishing; 2023.
  5. Ravi G, Kapoor P. Current approach to Waldenström Macroglobulinemia. CTARC. 2022;31:100527.
  6. Britannica. Bone marrow [Internet]. Accessed Sep 30 2023, via https://www.britannica.com/science/bone-marrow 
  7. NHS. Biopsy [Internet]. Last updated Aug 10 2021, accessed Sept 30 2023 via https://www.nhs.uk/conditions/biopsy/ 
  8. NHS. Stem cell transplant [Internet]. Last updated Sep 7 2022, accessed Sep 30 2023 via https://www.nhs.uk/conditions/stem-cell-transplant/
  9. Vasculitis Foundation. Cryoglobulinemia [Internet]. Accessed Sep 30 2023 via https://www.vasculitisfoundation.org/education/forms/cryoglobulinemia/ 
  10. Patient. Cold Agglutinins [Internet]. Last updated Aug 20 2014, accessed Sep 30 2023 via https://patient.info/doctor/cold-agglutinins
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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