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Bone marrow assessment in asymptomatic immunoglobulin M monoclonal gammopathies

In a recent issue of this journal, the British Committee for Standards in Haematology (BCSH) published the guidelines for diagnosis and management of Waldenstr€ om macroglobulinaemia (WM) (Owen et al, 2014). The experts recommend that bone marrow assessment should be included in the diagnostic work-up of all patients with an IgM monoclonal (M) protein, whatever the concentration, if there is a clinical suspicion of WM, based on the presence of typical signs and symptoms, such as cytopenias, lymphadenopathies, splenomegaly or symptoms related to the monoclonal (M) protein. The need of a bone marrow evaluation in asymptomatic patients is more controversial, especially if the concentration of the IgM M-protein is low. In 2009, a joint commission of the BCSH, the UK Myeloma Forum and the Nordic Myeloma Study Group stated that a routine bone marrow biopsy was not required in patients with a serum IgM M-protein lower than 10 g/l, unless there were symptoms of concern (Bird et al, 2009). However, as emphasized in the diagnostic criteria established during the Second International Workshop on WM (IWWM), the concentration of monoclonal IgM can vary widely in WM and it is not possible to define a concentration that reliably distinguishes WM from monoclonal gammopathy of undetermined significance (MGUS) (Owen et al, 2003). After the Second IWWM, we introduced bone marrow assessment into the diagnostic work-up of all patients with an IgM monoclonal protein, including those without symptoms and with low levels of M-protein. We retrospectively reviewed 177 consecutive patients with an asymptomatic IgM monoclonal gammopathy, seen at our Institution between 2002 and 2014, who provided their consent to bone marrow evaluation. Based on bone marrow findings, 113 patients (64%) were classified as IgM-MGUS and 64 (36%) as asymptomatic WM. The main clinical patients’ characteristics are reported in Table I. One hundred and forty-nine patients were evaluable for progression. Overall, 22 patients (15%) progressed to symptomatic WM treatment during their follow-up. The 5-year and 10-year progression-free survival (PFS) of patients with IgM-MGUS was respectively 90% and 81%, as compared to 61% and 46% in patients with asymptomatic WM (P = 0 001). We then focused on the 87 asymptomatic patients presenting with an IgM M-protein lower than 10 g/l, to assess