29th May 2023

Waldenstrom’s macroglobulinaemia

Waldenstrom’s is a type of indolent B-cell lymphoma called lymphoplasmacytic lymphoma (LPL), but one which secretes IgM (monoclonal) paraprotein. The malignant cells share features of both lymphoid cells and plasma cells. It is relatively rare and mostly presents in >70 years.  There is an association with Sjogren’s syndrome and autoimmune haemolytic anaemia.

There is usually bone marrow infiltration and there may be lymphadenopathy or splenomegaly. Symptoms can be diverse and may be related to anaemia from marrow infiltration, constitutional symptoms or lymphadenopathy or directly related to the IgM paraprotein (due to it being a large and ‘sticky’ protein):

1. Hyperviscosity syndrome – visual disturbances, neurological deficits, and skin/mucosal bleeding. Treatment is with fluids and urgent plasmapheresis.
2. Cryoglobulinaemia
3. Coagulation abnormalities
4. Cold haemagglutinin disease
5. Peripheral neuropathy

It is preceded by a premalignant IgM MGUS condition, with parallels to MGUS and myeloma.

Investigations

• Bloods
  • To include full panel plus serum Ig electrophoresis, may need hyperviscosity screen and DAT screen
• Bone marrow – essential for diagnosis
• Imaging – if symptomatic, CT CAP for staging should be performed

Treatment

Treatment is not always needed immediately. A ‘watch and wait’ approach is often taken initially. The following are indications to start treatment:

1. Constitutional symptoms
2. Symptomatic lymphadenopathy/splenomegaly
3. Hyperviscosity syndrome
4. Cytopenias due to marrow infiltration
5. IgM related syndromes – CHAD, peripheral neuropathy

Treatment is not generally considered curative. Overall median survival is 5 years from diagnosis.