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||Monoclonal Gammopathy of Undetermined Significance and Risk of Infections A Population Based Study
||Kristinsson SY, Min T, Pfeiffer R, Bjorkholm M, Goldin L, Blimark C, Mellqvist UH, Wahlin A, Turesson I, Landgren O
||2010 Nov 19
||Abstract 4053Background: Based on clinical case reports and small hospital-based patient series, monoclonal gammopathy of undetermined significance (MGUS) has been reported to increase morbidity due to bacterial infections; however, no comprehensive evaluation has been conducted.Patients and methods: Using population-based data from Sweden, we assessed the risks of viral and bacterial infections (reported to the Patient-Registry) in 5,326 MGUS patients diagnosed 1958-2006, compared to 20,161 matched population-based controls. We fit Cox proportional hazard models to estimate hazard ratios (HRs) as measures of risk.Results: At 5 years of follow-up MGUS patients had a 2.1-fold (95% confidence interval (CI) 2.1-2.3) increased risk of developing any infection compared to controls; at 10 years of follow-up, the risk was very similar (HR=2.2; 95% CI 2.0-2.3). MGUS patients had a 2.2-fold (95% CI 2.0-2.4) and 2.1-fold (95% CI 2.0-2.3) increased risk of developing bacterial infections at 5 and 10 years, respectively. A significantly increased risk (P<0.05) was found for pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis and meningitis. We also assessed the risk of developing viral infections; compared to controls, MGUS patients had a 2.7-fold (95% CI 2.2-3.3) and 2.9-fold (95% CI 2.3-3.7) increased risk at 5 and 10 years, respectively, with a significantly increased risk for influenza and herpes infections (P<0.05). Risk of infections did not differ by MGUS isotype. MGUS patients with an M-protein >2.5 g/dL at diagnosis had higher risks of infections compared to those <0.5 g/dL. However, compared to controls the risk of infections was also significantly increased among MGUS patients with a concentration <0.5 g/dL. MGUS patients with (versus without) infections had no excess risk of developing multiple myeloma or related malignancies.Summary and Conclusions: Based on over 5,000 MGUS patients, we found a 2-fold higher risk of developing bacterial and viral infections, compared to controls. The risk was highest among MGUS patients with high M-protein concentrations at diagnosis (>2.5 g/dL); however, the risk was still significantly increased among those with a concentration <0.5 g/dL. Infections in patients with MGUS were not associated with an increased risk of malignant transformation. We recently showed that patients with MGUS have a 3-fold risk of death in bacterial infections. Our findings may have clinical implications for treatment strategies and prophylactic measures, as well as surveillance of MGUS patients.