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. 2014 Sep 1;32(25):2699-704.
doi: 10.1200/JCO.2013.50.0892. Epub 2014 Jul 14.

Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis

Brendan M Weiss  1 , Joseph Hebreo  2 , Daniel V Cordaro  2 , Mark J Roschewski  2 , Thomas P Baker  2 , Kevin C Abbott  2 , Stephen W Olson  2
Affiliations

Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis

Brendan M Weiss et al. J Clin Oncol. .

Abstract

Purpose: Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis.

Patients and methods: We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples.

Results: An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001).

Conclusion: Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Receiver operator characteristic (ROC) curves for free light chain differential in years before diagnosis of immunoglobulin light chain amyloidosis. Free light chain differential for (A) < 4 years, (B) 4 to 11 years, and (C) > 11 years before diagnosis.
Fig 2.
Fig 2.
Serial free light chain (FLC) differential levels before clinical presentation in patients with immunoglubulin light chain amyloidosis.
Fig A1.
Fig A1.
Box plots representing free light chain (FLC) differential levels in cases and controls in the years before diagnosis of immunoglobulin light chain (controls = 0; cases = 1). FLC differential by case (A) < 4 years, (B) 4 to 11 years, and (C) > 11 years before diagnosis. The horizontal bar represents the median, vertical bars represent the highest and lowest values that are not outliers, and the dots are outliers (defined as outside 1.5 times the interquartile range). The lower and upper end of each box represents the first and third quartile, respectively. Interquartile range is defined as the third quartile subtracted from the first quartile.
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