23rd July 2024

Waldenström’s macroglobulinaemia (WM)

Background of WM

WM is an indolent B-cell lymphoma characterised by bone marrow infiltration of lymphoplasmacytic cells which secrete a monoclonal IgM into blood.

The median age of diagnosis is 70 years, with a higher incidence in males and Caucasians.

The specific aetiology of WM is unknown. A history of IgM MGUS or a first-degree relative with a B-cell lymphoproliferative disorder are the only known risk factors.

Presentation and diagnosis of WM

Some patients may be asymptomatic at presentation. Others may present with the following symptoms:

• Constitutional symptoms: fatigue, weakness, weight loss
• IgM paraproteinaemia: hyperviscosity syndrome (visual disturbance, headache, vertigo, tinnitus, bleeding), peripheral neuropathy (usually sensorimotor, distal, symmetric, slowly progressive, legs>arms), infections (reduced production of other Ig types)
• Tissue infiltration: anaemia, lymphadenopathy, hepatosplenomegaly
• Cryoglobulinaemia (discussed later)

Bone pain and bone lesions are rare in WM compared to MM.

Diagnosis requires blood tests, urine electrophoresis, bone marrow biopsy (with immunophenotyping) and imaging for disease staging. Blood tests include full blood count (anaemia), erythrocyte sedimentation rate (usually very high), serum immunoglobulins, serum protein electrophoresis and serum free light chains.

Management and prognosis of WM

Asymptomatic patients are considered to have smouldering WM and do not require treatment; they should be followed up every 3-6 months.

Symptomatic patients should be treated. WM is incurable, so treatment aims are to reduce symptoms and increase quality of life and survival. There is no standardised first-line therapy. Chemoimmunotherapy is normally used (e.g. bendamustine and rituximab).

Symptomatic hyperviscosity is a medical emergency that requires treatment with plasmapheresis.

Median survival is >10 years with many patients dying of causes unrelated to WM.