title: Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study.
abstract: Monoclonal gammopathy of undetermined significance (MGUS) is defined by expression of heavy-chain immunoglobulin (IgH) and is the precursor lesion for 80% of cases of multiple myeloma. The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS.
  
  
  
  We used a population-based cohort, previously assembled to estimate MGUS prevalence, of 21,463 residents of Olmsted County, MN, USA, aged 50 years and older. We did a serum free light-chain assay on all samples with sufficient serum remaining, and immunofixation electrophoresis was done for all samples with an abnormal free light-chain ratio or abnormal protein electrophoresis results from the original study. Light-chain MGUS was defined as an abnormal free light-chain ratio with no IgH expression, plus increased concentration of the involved light chain. We calculated age-specific and sex-specific prevalence and rates of progression to lymphoproliferative disorders for light-chain and conventional MGUS and assessed incidence of renal disorders in patients with light-chain MGUS.
  
  
  
  610 (3.3%) of 18,357 people tested had an abnormal free light-chain ratio, of whom 213 had IgH expression that was diagnostic of conventional MGUS. 146 of the remaining 397 individuals had an increase of at least one free light chain and met criteria for light-chain MGUS. Prevalence of light-chain MGUS was 0.8% (95% CI 0.7-0.9), contributing to an overall MGUS prevalence of 4.2% (3.9-4.5). Risk of progression to multiple myeloma in patients with light-chain MGUS was 0.3% (0.1-0.8) per 100 person-years. 30 (23%) of 129 patients with light-chain MGUS were diagnosed with renal disease.
  
  
  
  We define a clinical entity representing the light-chain equivalent of conventional MGUS and posing a risk of progression to light-chain multiple myeloma and related disorders.
  
  
  
  US National Cancer Institute.
authors.affiliation: Hematology, Mayo Clinic, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Katzmann
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Larson
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Melton
authors.forename: Colin L
authors.initials: CL
authors.lastname: Colby
authors.forename: Terry M
authors.initials: TM
authors.lastname: Therneau
authors.forename: Raynell
authors.initials: R
authors.lastname: Clark
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
authors.forename: Arthur
authors.initials: A
authors.lastname: Bradwell
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: D F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000097:blood; D007674:Kidney Diseases / Q000150:complications; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D009101:Multiple Myeloma / Q000209:etiology; D011230:Precancerous Conditions / Q000150:complications; D015995:Prevalence; D012307:Risk Factors
chemical_list: D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains
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