A monoclonal gammopathy of undetermined significance (MGUS) occurs in about 1% of the population over 50 years of age. Of these, about 20% evolves in Multiple Myeloma (MM); however, so far, predictive parameters of progression have not yet been identified.The aim of this study was to analyse the natural history of a cohort of non IgM MGUS and to identify whether or not there were laboratory parameters at diagnosis which can be utilized as prognostic markers of stable MGUS or progression to MM. From February 1974 to July 2001, 656 non IgM MGUS, whose clinical history was concluded (lost to follow up or died), have been followed at the Hematology of the University “La Sapienza” in Rome. The duration of follow up ranged from 2 months to 324 months, male/female ratio was 1.14, median age was 65 years (range 19–92). In each patient we evaluated: hemoglobin, platelet count, serum protein electrophoresis, serum concentration of monoclonal protein, serum calcium, creatinine, uric acid, BUN and percentage of bone marrow plasma cells.A monoclonal component (MC) of IgG type was documented in 543 patients (83%) while in 106 (16%) it was of IgA type, 6 patients had biclonal MC and 1 had a λ light chain MC; BJ proteinuria was detected in 78 (11%) patients at diagnosis.

After a median follow up of 60.1 months (range 2–324) the MC remained stable in 496 patients (75%), whereas in 160 cases (25%) increased to evolve in MM. According to the literature, cumulative probability of progression to MM was 3%, 7% and 17% at 5, 10 and 15 years respectively. Differently from what observed by other investigators, in this cohort of pts, the MGUS of IgA type was not associated with a higher risk of progression to MM. The median time of progression to MM was 60.7 months (range 3–256) and factors associated with a more rapid progression to MM were advanced age and a higher number of bone marrow plasmacells. At diagnosis of MM, the concentration of the serum MC was significantly higher (P<0.003) in patients who evolved from MGUS than in those with a newly diagnosed MM. None of the studied parameters at diagnosis of MGUS were predictive of evolution to MM even though, levels of MC <2.4 g/dl and bone marrow plasmacell infiltration <9% indicated a slower progression to overt MM.

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