These cases should have no symptoms or findings of end organ dysfunction attributed to Waldenström macroglobulinemia such as anemia, decreases in any white blood cell count, cold agglutinin disease, hyperviscosity of blood, lymphadenopathy, hepatomegaly, splenomegaly, peripheral neuropathy, cryoglobulinemia, or constitutional symptoms.As determined by a Mayo Clinic study of 48 individuals, smoldering Waldenström macroglobulinemias risk of progression to Waldenström macroglobulinemia is estimated to be ~12% per year and then falling of sharply for at least the next 5 years to 2% per year. In this study the only factor predictive of a more rapid progress was a finding of anemia (hemoglobin level <115 grams/liter). During a 15-year follow-up, the Clinic subsequently reported that patients progressed to Waldenström macroglobulinemia, amyloidosis, or a related IgM-associated neoplasm at a rate of 6%, 39%, 59%, and 68% after the first, third, fifth, and tenth year, respectively. However, the Southwest Oncology Group in a study on 231 individuals reported that the smoldering disease progressed to overt Waldenström macroglobulinemia over 9 years in only 26% of cases. Light chain SMM
Light chain smoldering multiple myeloma (light chain SMM) was previously termed idiopathic Bence Jones proteinuria. The condition is currently diagnosed in asymptomatic individuals who have a 24-hour urinary Bence Jones, i.e. light chain myeloma protein level, that is >0.5 grams and/or bone marrow plasma cells that are 10% to <60% of nucleated cells.
SMM consists of the following subtypes which represent progression of their corresponding MGUS subtypes. Non-IgM SMM
Non-IgM SMM (also termed IgG and IgA SMM because of the rarity of IgD and IgE SMM) is diagnosed in asymptomatic individuals based on criteria identical to those listed above for Non-IgM MGUS except that: their intact IgG or IgA myeloma protein levels are equal to or greater than 30 grams/liter rather than 15 grams/liter; their bone marrow shows plasma cells comprise between 10% and <60% rather than <10% of nucleated cells; and/or their 24-hour urine contains 0.5 gram or greater levels of Bence Jones, i.e. light chain myeloma, proteins. individuals must also lack evidence of more recently established multiple myeloma-defining criteria viz., CRAB features, amyloidosis, more than one solitary plasmacytoma, and/or serum or urine free light chain κ to λ or λ to κ ratios of 100 or greater.Overall, the risk of Non-IgM SMM progressing to multiple myeloma is 10% per year for the first 5 years but falls off sharply to 3% per year for the next 5 years and thereafter to 1% per year. Smoldering Waldenström macroglobulinemia
Smoldering Waldenström macroglobulinemia is diagnosed in asymptomatic individuals that have a serum IgM level 30 gram/liter and/or a bone marrow lymphoplasmacytoid cell infiltrate >10% of total nucleated cells.