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Summary:

  • Waldenström's macroglobulinaemia is a rare lymphoplasmacytic lymphoma associated with the production of monoclonal IgM.
  • sFLC analysis is informative in the majority of patients at diagnosis.
  • Elevated concentrations of FLCs at baseline are associated with shorter time to treatment and reduced overall survival.
  • The involved FLC concentration is a useful marker of response to treatment and may show responses and disease progression earlier than IgM.
  • Quantification by IgM Hevylite® may be useful in cases where the monoclonal protein concentration is low, forms multimers or co-migrates with other serum protein peaks.
  • IgM Hevylite may be useful for monitoring responses to treatment and identifying patients with inferior survival.

Waldenström's macroglobulinaemia (WM) is a rare, low-grade, lymphoplasmacytic lymphoma characterised by the production of monoclonal IgM. The incidence rate of WM is approximately 5 cases per million persons per year, about 5 - 10% that of multiple myeloma (MM) [704]. The median age at diagnosis is 65 years, and up to 70% of patients are male [704][705] Median survival is approximately 5 years (with 10% of patients still alive after 15 years); many die from unrelated causes [705]. The majority of patients diagnosed with WM do not require immediate therapy as they are detected before symptoms occur [706].

Infiltration of bone marrow and extramedullary sites by malignant B-cells, and elevated serum IgM concentrations are responsible for the majority of symptoms associated with WM [707]. Whilst the most common presenting symptom is fatigue related to anaemia, symptoms vary considerably among patients and may include night sweats, weight loss, bleeding tendency, polyneuropathy, lymphadenopathy, hepatosplenomegaly and symptoms relating to hyperviscosity (i.e. headaches, blurred vision, confusional episodes, epistaxis).

Cryoglobulinaemia (where monoclonal IgM reversibly precipitates at temperatures below 37 °C) affects up to 20% of patients, although <5% have symptoms (Section 34.2) [707]. The presence of cryoglobulins makes serum collection and laboratory quantification of IgM difficult, as they need to be performed at elevated temperatures.

Attempts to standardise diagnostic criteria have been made by the World Health Organisation (WHO) and the Mayo Clinic (Table 32.1), but there are significant discrepancies between the two definitions [704].

Mayo Clinic WM diagnostic criteria:

▪ IgM monoclonal gammopathy (regardless of the size of the monoclonal protein).

▪ >10% bone marrow lymphoplasmacytic infiltration (usually inter-trabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation.

▪ Tumour lymphocytes display a typical immunophenotype (surface IgM+, CD5-, CD10-, CD19+, CD20+, CD23-) that satisfactorily excludes other lymphoproliferative disorders, including chronic lymphocytic leukaemia and mantle cell lymphoma.

Table 32.1. Mayo Clinic WM diagnostic criteria [704][708].