Dispenzieri, A. et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 23, 215-224

Department of Hematology/Laboratory Medicine/Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K (Impact Factor: 10.43). 12/2008; 23(2):215-24. DOI: 10.1038/leu.2008.307
Source: PubMed


The serum immunoglobulin-free light chain (FLC) assay measures levels of free kappa and lambda immunoglobulin light chains. There are three major indications for the FLC assay in the evaluation and management of multiple myeloma and related plasma cell disorders (PCD). In the context of screening, the serum FLC assay in combination with serum protein electrophoresis (PEL) and immunofixation yields high sensitivity, and negates the need for 24-h urine studies for diagnoses other than light chain amyloidosis (AL). Second, the baseline FLC measurement is of major prognostic value in virtually every PCD. Third, the FLC assay allows for quantitative monitoring of patients with oligosecretory PCD, including AL, oligosecretory myeloma and nearly two-thirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial FLC measurements outperform PEL and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial FLC measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using FLC assay in place of 24-h urine PEL for monitoring or for serial measurements in PCD with measurable disease by serum or urine PEL. This paper provides consensus guidelines for the use of this important assay, in the diagnosis and management of clonal PCD.

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Available from: Piero Tosi
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    • "During the past decade the serum free light chain (FLC) immunoassays have become widely available enabling greater sensitivity in the diagnosis and management of monoclonal light chain diseases [1, 2]. These assays have proved to be particularly beneficial for the detection of monoclonal FLCs in patients previously considered to be nonsecretory according to electrophoresis [3]. "
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    ABSTRACT: In the past decade, the serum free light chain (FLC) immunoassays have become widely available enabling greater sensitivity in the diagnosis and management of monoclonal light chain diseases. Here, we describe a rare case of serum free light chain only myeloma with cytoplasmic IgM. A 75-year-old woman presented with a progressively worsening lumbosacral pain. FDG PET/CT images showed increased FDG uptake in the sacral mass, vertebral bodies, and ribs. Laboratory data found hypogammaglobulinemia and the bone marrow aspirate revealed only 2.2% of plasma cells. The serum and urine protein electrophoresis did not detect a monoclonal band. However, the serum FLC immunoassays reported an abnormal kappa/lambda ratio (0.001) indicating the presence of monoclonal lambda FLC. The sacral tumor biopsy revealed proliferation of plasma cells and immunohistochemical staining showed that the plasma cells were positive for CD138, IgM, and lambda light chain but negative for CD20. This case may have previously been described as a nonsecretory IgM myeloma but recently would be identified as free light chain only myeloma. The immunohistochemical and genetic features of the clonal plasma cells in free light chain only myeloma need to be further investigated to better understand the relevance and incidence of this myeloma type.
    Full-text · Article · Jun 2014
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    • "On comparing the FLC levels according to the group, the kappa FLC showed high correlation in both groups, with the correlation coefficient being greater than 0.95, and the lambda FLC of the MG group also showed the correlation coefficient, 0.8. The κ/λ ratio of the non-MG group showed the lowest correlation, r = 0.52, and this is in line with the international guidelines, according to which changes in the ratio in the normal ranges should not be considered as clinically significant [3, 4]. In a previous study that compared the two assays, correlation coefficients were around 0.9 for kappa and 0.7 for lambda and κ/λ ratio, indicating that the current study had relatively better outcomes [9]. "
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    ABSTRACT: Free light chains (FLCs) are useful biomarkers for the diagnosis and monitoring of various plasma cell dyscrasias. One hundred fifty-seven samples from 120 patients for screening or monitoring of monoclonal gammopathy (MG) were included. The new N Latex FLC assays (Siemens Healthcare Diagnostics GmbH, Germany) were compared with the Freelite FLC assays (The Binding Site Ltd., UK) and the results were analyzed with those of immunofixation electrophoresis (IFE). The Freelite FLC assay showed significantly wider assay ranges than the N Latex FLC assay. The correlation coefficients of the two FLC kappa ( κ ) assays, lambda ( λ ) assays, and the κ / λ ratio were 0.9792, 0.8264, and 0.9064, respectively. The concordance rate was 84.7% for the FLC κ assays, 79.6% for FLC λ , and 89.2% for the κ / λ ratio. The clinical sensitivity and specificity of the κ / λ ratios were 72.2% and 93.6% for the Freelite assay and 64.6% and 100% for the N Latex FLC assay. Two FLC assays showed good correlations and concordance. However, the clinical sensitivity of the κ / λ ratio was higher in the Freelite FLC assays; clinical specificity was higher in the N Latex FLC assay. Both FLC assays seem to have limited clinical utility in detecting MG in certain clinical settings.
    Full-text · Article · May 2014 · BioMed Research International
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    • "As immunoglobulin synthesis is a hallmark of MM, increased 11C-MET retention might thus be explained by at least partial incorporation into (para-) proteins, as has been shown for other tumor entities [25,26]. Molecules mediating the interaction between myeloma cells and bone marrow stromal cells, immunoglobulin levels and cytogenetic alterations are important determinants of myeloma pathology and serve as markers for disease activity and/or aggressiveness [27-31]. Based on this, the potential association of CD138, CXCR4 and intracellular immunoglobulins with 11C-MET uptake we found here, might allow for non-invasive risk stratification of the individual patient and response monitoring using imaging with PET/CT. "
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    ABSTRACT: Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of (18)F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[(11)C]-methionine ((11)C-MET) and [(18)F]-fluoroethyl-L-tyrosine ((18)F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. To study the utility of (11)C-MET, (18)F-Fet and (18)F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138(+) plasma cells were characterized regarding uptake and biomedical features. Using myeloma cell lines and patient-derived CD138(+) plasma cells, we found that the relative uptake of (11)C-MET exceeds that of (18)F-FDG 1.5- to 5-fold and that of (18)F-Fet 7- to 20-fold. Importantly, (11)C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of (11)C-MET. These data suggest that (11)C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with (18)F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.
    Full-text · Article · Dec 2013 · PLoS ONE
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