Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study

Angela Dispenzieri; Jerry A. Katzmann; Robert A. Kyle; Dirk R. Larson; L. Joseph Melton; Colin L. Colby; Terry M. Therneau; Raynell Clark; Shaji K. Kumar; Arthur Bradwell; Rafael Fonseca; DF F. Jelinek; S. Vincent Rajkumar

doi:10.1016/S0140-6736(10)60482-5

Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study

Angela Dispenzieri, Jerry A. Katzmann, Robert A. Kyle, Dirk R. Larson, L. Joseph Melton, Colin L. Colby, Terry M. Therneau, Raynell Clark, Shaji K. Kumar, Arthur Bradwell, Rafael Fonseca, DF F. Jelinek, S. Vincent Rajkumar

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Abstract

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: US National Cancer Institute.

Original language	English (US)
Pages (from-to)	1721-1728
Number of pages	8
Journal	The Lancet
Volume	375
Issue number	9727
DOIs	https://doi.org/10.1016/S0140-6736(10)60482-5
State	Published - 2010

ASJC Scopus subject areas

General Medicine

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10.1016/S0140-6736(10)60482-5

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Dispenzieri, A., Katzmann, J. A., Kyle, R. A., Larson, D. R., Melton, L. J., Colby, C. L., Therneau, T. M., Clark, R., Kumar, S. K., Bradwell, A., Fonseca, R., Jelinek, DF. F., & Rajkumar, S. V. (2010). Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. The Lancet, 375(9727), 1721-1728. https://doi.org/10.1016/S0140-6736(10)60482-5

Dispenzieri, A, Katzmann, JA, Kyle, RA, Larson, DR, Melton, LJ, Colby, CL, Therneau, TM, Clark, R, Kumar, SK, Bradwell, A, Fonseca, R , Jelinek, DFF & Rajkumar, SV 2010, 'Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study', The Lancet, vol. 375, no. 9727, pp. 1721-1728. https://doi.org/10.1016/S0140-6736(10)60482-5

@article{3852d1f8398a48d2ad84cf61fc764a47,

title = "Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study",

abstract = "Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: US National Cancer Institute.",

author = "Angela Dispenzieri and Katzmann, {Jerry A.} and Kyle, {Robert A.} and Larson, {Dirk R.} and Melton, {L. Joseph} and Colby, {Colin L.} and Therneau, {Terry M.} and Raynell Clark and Kumar, {Shaji K.} and Arthur Bradwell and Rafael Fonseca and Jelinek, {DF F.} and Rajkumar, {S. Vincent}",

note = "Funding Information: Investigators were supported in part by the US National Cancer Institute (grant numbers CA125614, CA062242, CA107476, CA150831, CA93842, CA83724, CA100080, and CA100707 ) and National Institutes of Health ( AR30582 ). Support was also provided by the Robert A Kyle Hematologic Malignancies Fund. We thank The Binding Site, UK, for providing reagents and Tara Phelps and Carol Shipman for their work maintaining the samples and the Dysproteinemia database, respectively. ",

year = "2010",

doi = "10.1016/S0140-6736(10)60482-5",

language = "English (US)",

volume = "375",

pages = "1721--1728",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9727",

}

TY - JOUR

T1 - Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance

T2 - a retrospective population-based cohort study

AU - Dispenzieri, Angela

AU - Katzmann, Jerry A.

AU - Kyle, Robert A.

AU - Larson, Dirk R.

AU - Melton, L. Joseph

AU - Colby, Colin L.

AU - Therneau, Terry M.

AU - Clark, Raynell

AU - Kumar, Shaji K.

AU - Bradwell, Arthur

AU - Fonseca, Rafael

AU - Jelinek, DF F.

AU - Rajkumar, S. Vincent

N1 - Funding Information: Investigators were supported in part by the US National Cancer Institute (grant numbers CA125614, CA062242, CA107476, CA150831, CA93842, CA83724, CA100080, and CA100707 ) and National Institutes of Health ( AR30582 ). Support was also provided by the Robert A Kyle Hematologic Malignancies Fund. We thank The Binding Site, UK, for providing reagents and Tara Phelps and Carol Shipman for their work maintaining the samples and the Dysproteinemia database, respectively.

PY - 2010

Y1 - 2010

N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: US National Cancer Institute.

AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: US National Cancer Institute.

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U2 - 10.1016/S0140-6736(10)60482-5

DO - 10.1016/S0140-6736(10)60482-5

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SN - 0140-6736

VL - 375

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JO - The Lancet

JF - The Lancet

IS - 9727

ER -

Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study

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