Prognostic validation of the international classification of immunoglobulin M gammopathies: A survival advantage for patients with immunoglobulin M monoclonal gammopathy of undetermined significance?

Purpose: To verify the reliability of the new criteria for the diagnosis of IgM gammopathies recently proposed by an international panel of experts (Athens, 2002). Experimental Design: A retrospective series of 698 patients with IgM gammopathy was reviewed paying attention to symptoms, serum IgM concentration, bone marrow infiltration, blood cell count and clinical course. Four clinical entities can be identified: IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), asymptomatic and symptomatic Wandenström's macroglobulinemia (A-WM and S-WM, respectively), and IgM-related disorders, although this last was excluded from the study because of the scarcity of patients due to probable selection biases. The observed mortality was studied related to that expected in the general population of comparable age and ses and over an equivalent period of follow-up (standardized mortality ratio, SMR). Results: IgM-MGUS, A-WM, and S-WM shared many clinical aspects but, with respect to the general population, patients with IgM-MGUS had a slight but definite survival advantage, those with A-WM had a mortality rate equivalent to that of the general population, whereas the SMR of patients with S-WM was 5.4. Within A-WM and S-WM the SMR values did not vary significantly in relation to marrow lymphocyte counts or serum IgM concentrations. Conclusions: Our findings represent a prognostic validation of the applied diagnostic criteria for three of the four identifiable clinical entities and highlight the importance of symptoms over serum IgM concentration and marrow infiltration.