Waldenström’s Macroglobulinemia (WM)
Characteristics
Waldenström’s macroglobulinemia, also called lymphoplasmacytic lymphoma, is a slow-growing (indolent) non-Hodgkin lymphoma (NHL) that originates from lymphocytes with features between B-cells and plasma cells. Due to mutations in these cells, an excess amount of a protein called immunoglobulin M (IgM) is produced. This excessive amount of IgM thickens the blood and reduces the blood flow. This process is referred to as hyper-viscosity syndrome. In parallel, the cancerous B-cells start to grow out of control, building up in the bone marrow and disturbing the normal production of blood cells.
WM typically affects older people (≥65 years) and is slightly more common in men than in women. WM is a rare cancer type, with about 190 new diagnoses in Belgium in 2021. For the moment, there is no cure for WM, but effective treatments have been developed that can keep the disease under control for many years.
Patient materials
Uitklappen
Certain genetic changes in the DNA of B-lymphocytes trigger the development of WM. The most common of these mutations involves the MYD88 gene (seen in about 90% of WM patients). This gene is responsible for the production of the MYD88 protein, which plays an important role in regulating the protein production. In addition to this, about 40% of WM patients carry a mutation in the CXCR4 gene, which produces a protein with a crucial role in regulating the cell growth and cell division.
Symptoms
Usually, WM follows an indolent disease course and the disease can remain asymptomatic for years. When WM does become symptomatic, some of the symptoms are similar to what is seen in other types of NHL, including an unexplained weight loss, fever, and drenching night sweats (B-symptoms).
In addition to this, a disturbed blood cell production can lead to a general feeling of weakness and fatigue (due to a reduced number of red blood cells), a tendency to bleed or bruise easily (due to a reduced number of platelets) and being prone to infections (due to a reduced number of white blood cells).
Also the excessive IgM production and the resulting hyperviscosity syndrome can cause a specific set of symptoms. For example, excessive amounts of IgM can damage nerves in the extremities, leading to numbness, or a tingling sensation in fingers and toes (neuropathy). In addition to this, the thickened blood can cause nosebleeds, dizziness, or headaches and a blurred vision.
A proportion of WM patients may also develop swollen lymph nodes, or an enlarged spleen or liver.
Diagnostic tests
The diagnosis of WM requires several analyses. First of all, a blood sample will be collected to assess the number of healthy blood cells and to measure the level of IgM protein in the blood. The abnormal IgM antibody that is made in WM is monoclonal, meaning that it concerns many copies of an identical antibody. The identification of such a monoclonal antibody is mandatory for a diagnosis of WM. To this end, a serum protein electrophoresis (or SPEP) test is performed on a blood (or urine) sample.
To confirm the WM diagnosis, cancer cells need to be present in the bone marrow. To this end, a bone marrow sample is removed from the hipbone or sternum (breastbone) and sent to the lab for a further evaluation of the size, shape, and molecular and genetic features of the cells in the bone marrow.
In addition to this, imaging tests (X-ray, CT, PET, MRI, ultrasound) can be performed to look for signs of WM in other areas of the body.
Treatments
For patients without symptoms, a "watch-and-wait" approach is often adopted. This means that patients don’t get any treatment but are followed up with regular blood tests to monitor the disease and the overall health of the patient.
When treatment is necessary (usually when anaemia or B-symptoms occur), targeted therapy with an inhibitor of the Bruton’s tyrosine kinase (BTK), alone or in combination with the monoclonal antibody rituximab is currently the preferred first line treatment. In selected patients, chemotherapy and an autologous stem cell transplantation can be considered. In addition to this, clinical trials can offer patients a chance to be treated with alternative therapies.
To address the hyperviscosity syndrome, plasmapheresis can be used. With this procedure, blood is run through a machine to remove the IgM antibody, after which the blood is returned to the patient.
Relevant patient organisations
Get connected to different patient organisations that connect you to people with the same medical history. Support amongst peers helps the burden and stress of the daily challenges that come with disorders.
Find below some organisations we can recommend.
Be aware that these groups operate mainly in Dutch or French given their local nature, don’t hesitate to contact them nevertheless.
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