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MarjattaSinisalo
OutiLaine

Waldenström's Macroglobulinaemia (WM)

Essentials

  • Remember Waldenström's macroglobulinaemia as a rare cause of a increased ESR.
  • In most cases a long-term disease; progression may be very slow
  • Basically a lymphoma disease (lymphoplasmacytic lymphoma); defined as WM when paraprotein of IgM class is detected
  • Clinical picture is characterized by symptoms of cytopenias and immunodeficiency, by extramedullary tumour infiltrates and by hyperviscosity symptoms, often neuropathy.
  • No osteolytic lesions

Definition

  • Clonal proliferation of mature B cells (differentiation at the lymphocyte-plasma cell level) with a homogeneous immunoglobulin fraction (paraprotein, M component) detected in serum protein electrophoresis. This always consists of IgM.

Epidemiology

  • Far less frequent than myeloma, incidence about 0.3 new cases/100 000 persons/year
  • Usually occurs in persons aged 60-70 years, very rare in younger persons.
  • Slightly more common in men (60% of the cases).

Aetiology

  • Unknown; an association of chronic immunostimulation and autoimmune diseases with the disease onset has been suspected.

Diagnostic criteria

  • Lymphoplasmacytic lymphoma as a finding in the bone marrow and a serum IgM paraprotein.

Differential diagnosis

  • Other conditions with IgM paraprotein:
    • IgM-MGUS (monoclonal IgM-gammopathy of undetermined significance, drawing the line between IgM-MGUS and WM is difficult)
    • Extremely rare IgM myeloma (osteolytic bone lesions suggest myeloma)
    • B-lymphocytic neoplasms (chronic lymphatic leukaemia, diffuse lymphoma)

Clinical picture and laboratory findings

  • Each symptom occurs in about 20-25% of the patients
    • Deteriorated general condition
    • Bleeding
    • Splenomegaly
    • Hepatomegaly
    • Lymphadenopathy
    • Symptoms related to hyperviscosity: visual disturbances, headache, dizziness and other symptoms related to cerebral circulation
    • Neurological symptoms: distal symmetric slowly-progressing sensorimotor polyneuropathy
  • Laboratory findings
    • High ESR
    • Paraprotein in serum protein electrophoresis which in immunofixation is typed as IgM
    • Increased serum viscosity can be detected in about 50% of the patients, if IgM > 40 g/l (the investigation is rarely needed in follow-up, obtaining the result involves a delay).
    • Often anaemia or thrombocytopenia
    • High paraprotein concentration may cause erratic laboratory test results (e.g. sodium, creatinine, urea, cholesterol, bilirubin, LD, CRP).

Primary investigations

  • Complete automated blood count and bone marrow aspiration
  • Serum protein electrophoresis (immunofixation should be performed if paraprotein is detected)
  • Plasma IgG, IgA and IgM
  • Plasma creatinine and serum urate
  • Chest x-ray and upper abdominal ultrasonography

Course of the disease and prognosis

  • The course of the disease varies greatly; the average life expectancy is 5-6 years. Good response to therapy improves the prognosis.
  • WM usually is a long-lasting disease and its progression may be very slow.

Complications

  • Hyperviscosity syndrome (usually associated witha high IgM concentration, > 50 g/l)
  • Cryoglobulinaemia
  • Chronic cold agglutination disease: IgM paraprotein may act as a cold agglutinin and cause haemolytic anaemia.
  • Haemorrhages and infections

Treatment and follow-up , Bendamustine for Patients with Indolent B Cell Lymphoid Malignancies Including Chronic Lymphocytic Leukaemia

Evidence Summaries