Waldenström's macroglobulinaemia

Waldenström's macroglobulinaemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men.

The pathophysiological hallmark is monoclonal immunoglobulin M (IgM) production by malignant lymphoplasmacytic cells that infiltrate the bone marrow and visceral organs.

Diagnosis is most often made following an incidental finding of an IgM monoclonal protein (paraprotein) on a blood test.

Anaemia (due to marrow infiltration), fatigue, and anorexia are the most common clinical features.

Lymphadenopathy, splenomegaly, and hyperviscosity (which can lead to skin and mucosal bleeding, thrombosis, retinopathy with visual disturbances, and neurological symptoms such as headache, dizziness, and vertigo) are uncommon, but they are important clinical manifestations that require urgent treatment.

WM is incurable but median overall survival is long (approximately 8 years based on US data, though this will have improved significantly with the use of Bruton’s tyrosine kinase inhibitors and other novel agents).

Goals of treatment are to reduce symptoms, improve quality of life, and prolong survival. Treatment options include observation (for asymptomatic patients), plasmapheresis, chemotherapy, and targeted therapies.

There is no standard of care, mainly due to a lack of randomised trials in WM. Participation in clinical trials is recommended where possible.

WM can transform to aggressive high-grade lymphomas.

WM (also referred to as lymphoplasmacytic lymphoma [LPL]) is an indolent B-cell lymphoma in which malignant lymphoplasmacytic cells infiltrate bone marrow and visceral organs, and hypersecrete an IgM monoclonal protein.

Clinical manifestations are most commonly related to bone marrow infiltration by malignant cells (e.g., anaemia, thrombocytopenia, pancytopenia). They are less commonly related to organ infiltration (e.g., splenomegaly, hepatomegaly, and lymphadenopathy) and abnormal IgM properties and/or organ deposition (e.g., hyperviscosity syndrome, polyneuropathy, cryoglobulinaemia, cold agglutinin haemolytic anaemia, bleeding from the nose and gums, purpura, thrombosis [e.g., stroke, angina, myocardial infarction, pulmonary embolism, deep vein thrombosis], and kidney disease). In contrast with multiple myeloma, bone lesions are not a feature of WM.