Use of nonclonal serum immunoglobulin free light chains to predict overall survival in the general population.
OBJECTIVE
To determine whether the free light chain (FLC) assay provides prognostic information relevant to the general population.


METHODS
After excluding persons with a known plasma cell disorder, we studied 15,859 Olmsted County, Minnesota, residents 50 years or older in whom unmasked data and samples for FLC testing were available. Baseline information was obtained between March 13, 1995, and November 21, 2003, and follow-up status and cause of death were identified through June 30, 2009. The κ and λ FLC sum (Σ FLC) was evaluated for its ability to predict overall survival. Specific causes of death were also investigated.


RESULTS
In 158,003 person-years of follow-up, 4348 individuals died. A high Σ FLC was significantly predictive of worse overall survival; the risk ratio for death for those with the highest decile of Σ FLC (ie, ≥ 4.72 mg/dL) was 4.4 (95% confidence interval, 4.1-4.7) relative to the remaining study participants. Multivariate analyses demonstrated that this excess risk of death was independent of age, sex, and renal insufficiency, with a corrected risk ratio of 2.1 (95% confidence interval, 1.9-2.2). The increased mortality was not restricted to any particular cause of death because the observed-to-expected risk of death from most causes was significantly higher among those individuals with an antecedent Σ FLC of 4.72 mg/dL or higher, which is near the upper limit of normal for the test.


CONCLUSIONS
A nonclonal elevation of Σ FLC is a significant predictor of worse overall survival in the general population of persons without plasma cell disorders.
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
Angela
A
Dispenzieri
Jerry A
JA
Katzmann
Robert A
RA
Kyle
Dirk R
DR
Larson
Terry M
TM
Therneau
Colin L
CL
Colby
Raynell J
RJ
Clark
Graham P
GP
Mead
Shaji
S
Kumar
L Joseph
LJ
Melton
S Vincent
SV
Rajkumar
D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000097:blood*; D007146:Immunoglobulin lambda-Chains / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D009026:Mortality; D015999:Multivariate Analysis; D011379:Prognosis
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains