A 63-year-old man with a past history of ischaemic heart disease, diabetes and hypertension presented to his local Accident and Emergency department with a severe nose bleed. He also gave a 6-month history of intermittent headache, dizziness and blurring of vision. He was admitted by the ear, nose and throat surgeons but his nose bleeding proved difficult to control with local measures. Initial investigations revealed the following: haemoglobin 7.3 g/dl, white cell count 5.2 × 109/l with a normal differential and platelet count 97 × 109/l. The blood film demonstrated marked rouleaux formation and his plasma viscosity was grossly elevated at 10.3 mPa.s. Renal and hepatic function were essentially normal but serum protein electrophoresis demonstrated an immunoglobulin M (IgM) κ paraprotein level of 75 g/l. This was not associated with any reduction in the levels of IgG or IgA but κ light chains were present in the urine at low concentrations. Serum β2-microglobulin was elevated at 5 mg/l. Bone marrow examination demonstrated extensive infiltration by small lymphocytes showing plasmacytoid differentiation and a striking increase in reactive mast cells. The infiltrate had the following immunophenotype: CD5–, CD10–, CD19+, CD20+, CD22+, CD23–, CD79+, surface IgM κ+. A diagnosis of Waldenström's macroglobulinaemia (WM) was made.
What would be your initial management plan and chemotherapeutic options?
What are the known prognostic factors in this disorder?
Waldenström’s macroglobulinaemia is a relatively rare B-cell lymphoproliferative disorder, which is characterized primarily by bone marrow infiltration and IgM paraproteinaemia.1 It accounts for approximately 2% of all haematological malignancies. In the USA the annual incidence is 6.1 per million in white males and 2.5 per million in white females, although the incidence appears to be lower in non-Caucasians. In the UK the annual incidence is 10.3 per million while the median age at presentation is 71 years and the median overall survival is 60 months.2, 3 The presenting clinical features of WM are highly variable.2, 4, 5 Some patients are asymptomatic at presentation and are found to have an IgM paraprotein as a coincidental finding during unrelated clinical investigations.5, 6 Patients with symptomatic disease may present with features attributable to tissue infiltration such as anaemia, systemic symptoms and organomegaly. A proportion of patients present with clinical features directly attributable to the physicochemical properties of their IgM paraprotein. These features include hyperviscosity syndrome (see below), cryoglobulinaemia and amyloidosis. The IgM paraprotein may also have autoantibody specificity, which can result in a number of autoimmune phenomena such as peripheral neuropathy, cold agglutinin disease, immune thrombocytopenia, acquired von Willebrand’s disease and C1 esterase inhibitor deficiency (Caldwell syndrome).
Waldenström’s macroglobulinaemia is characterized by bone marrow infiltration by small lymphocytes showing plasma cell differentiation. The pattern of infiltration is diffuse or interstitial and a reactive increase in mast cells is ...