The Natural History of Monoclonal Gammopathy of Undetermined Significance

Abstract

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum monoclonal component (M-component), but no evidence of multiple myeloma, macroglobulinaemia, amyloidosis or other plasma cell proliferative disease. A long-term follow-up study (median 11.5 years) has been carried out in 263 cases of MGUS, 159 males (60.5%) and 104 females (39.5%), aged 40-89 years (median 66.5 years). The actuarial probability for malignant transformation was 6.1, 15.4 and 31.3% at 5, 10 and 20 years, respectively. At the final evaluation, 157 patients (59.7%), 119 (45.3%) of whom with no increase and 38 (14.4%) with an increase in serum M-component, died of causes unrelated to MGUS and without development of any plasma cell proliferative disease; 47 patients (17.9%) were still alive without increase in M-component; 11 patients (4.1 %) were still alive and at follow-up presented values of serum M-component > 30 g/l without any evidence of plasma cell proliferative or lymphoproliferative disease; 48 patients (18.3%) developed multiple myeloma (35 cases, 13.1%), solitary plasmacytoma of the bone (2 cases, 0.8%), macroglobulinaemia (4 cases, 1.6%), malignant lymphoma (3 cases, 1.2%), amyloidosis (2 cases, 0.8%), chronic lymphocytic leukaemia (1 case, 0.4%), and plasma cell leukaemia (1 case, 0.4%). The patients developing multiple myeloma, solitary plasmacytoma, macroglobulinaemia and plasma cell leukaemia had an increase in serum M-component, whereas no increase was found in malignant lymphoma, amyloidosis and chronic lymphocytic leukaemia. These findings and the data in the literature suggest that MGUS could be considered a preneoplastic condition; since no clinical and laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up indefinitely.

Long-term follow-up of IgM monoclonal gammopathy of undetermined significance

“…Macroglobulinemia was diagnosed at a median of 6 years after the recognition of MGUS, whereas MGUS had been present for 6, 13, and 15 years in 3 patients in whom malignant lymphoma developed. 25 Duration and results of follow-up were not given in a series of 106 patients with IgM paraprotein, of whom 22 had IgM MGUS. 26 In a report of 242 patients with MGUS of the IgM type diagnosed at Mayo Clinic from 1956 to 1978, 9 malignant lymphoid disorders developed in 40 (17%) patients an average of 4 years after recognition of the M protein.…”

Pathogenesis and progression of monoclonal gammopathy of undetermined significance

“…7,31,[53][54][55][56][57][58][59] No reliable predictors of progression were found in the first Mayo Clinic series 7 and in the studies with relatively small number of patients. 7,56 However, in the series including a larger number of cases, three features emerged as important predictors of progression: (a) the serum M-protein size, (b) the extent of bone marrow involvement by plasma cells and (c) the IgA M-protein isotype (Table 4).…”

Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study

“…10,12,13 However, to our knowledge, no population-based, large study has been conducted to determine excess mortality patterns and simultaneously assess causes of death in MGUS patients compared to those in controls. Using population-based and hospital-based registries from Sweden, we identified a nationwide cohort of 4,259 MGUS patients diagnosed in 1986-2005.…”