A Long-Term Study of Prognosis on Monoclonal Gammopathy of Undetermined Significance.

From 1976 to 2006, 547 patients have been identified and followed for monoclonal gammopathy of undetermined significance (MGUS). Criteria of inclusion included presence of serum monoclonal protein of a concentration of 2 g per deciliter or less; no or moderate amounts of monoclonal light chains in the urine; the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and proportion of plasma cells in the bone marrow of 5% or less. Patients identified as MGUS were followed every 6 months with physical examination, CBC, chemistries, and paraprotein studies. Ages ranged from 32 – 100 years (median 70 years). There were 214 males and 333 females. Over the 30 years of observation, 61 patients have developed disease progression: myeloma 29, lymphoma 12, macroglobulinemia 10, chronic lymphocytic leukemia 7, and amyloid 3. Time to develop myeloma ranged from 2–24 years (median 6 years), macroglobulinemia 2–8 years (median 5 years), and amyloid 3–10 years (median 10 years). Patients developed myeloma throughout the entire period of observation: 2, 3, 3, 4, 4, 4, 4, 5, 5, 5, 6, 6, 6, 6, 6, 7, 7, 8, 8, 9, 10, 10, 11, 14, 15, 15, 18, 20, and 24 years. Survival from diagnosis of myeloma was 1+ – 14+ months (median 36 months) for myeloma and 24 – 108+ months (median 48 months) for macroglobulinemia. The only reliable method of identifying progression of disease to myeloma/macroglobulinemia/amyloid was serial determinations of paraprotein level. In this large series followed for 30 years, with a more restricted diagnosis of MGUS (paraprotein level ≤ 2 g per deciliter and 5% or less bone marrow plasma cells), 1% of all patients identified developed progression of disease. No patient developed disease progression in less than 2 years using the more restricted diagnosis. Risk of progression increased with time with patients developing myeloma even 20 years or longer of follow-up. Serial evaluations of paraprotein levels are indicated in patients identified as MGUS.