Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
-
Charlotte Toftmann Hansen
Abstract
Measurements of immunoglobulins and serum free light chains (sFLC) are frequently used in patients with monoclonal plasma cell dyscrasia (PCD). For optimum patient care, well-defined performance standards or goals for the measured concentrations of immunoglobulins and sFLC are required. Generally, data based on biological variation is a good and reliable method for setting desirable performance standards; this also applies for the measurements of paraprotein and sFLC. The benefits of this approach are several. Among others, it is independent of the clinician, and it provides us with information about reference change value and index of individuality. Several studies on biological variation of both immunoglobulins and sFLC have been published, and mostly the studies are well performed. The studies normally show small within-subject biological variation resulting in strict analytical goals, which in most cases are difficult to meet. Nevertheless, we still need further information on biological variation of immunoglobulins and sFLC in patients with PCD and in the elderly, which are the main target populations for the two measurands. Furthermore, to improve data on biological variation of immunoglobulins and sFLC, studies accounting for number of individuals, samples, and replicates, as well as time length of the studies are needed.
References
1. Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215–24.10.1038/leu.2008.307Search in Google Scholar PubMed
2. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.10.1038/sj.leu.2404284Search in Google Scholar PubMed
3. Kallner A, McQueen M, Heuck C. The Stockholm Consensus Conference on quality specifications in laboratory medicine, 25 -26 April 1999. Scand J Clin Lab Invest 2015;59:475–6.10.1080/00365519950185175Search in Google Scholar PubMed
4. Sandberg S, Fraser CG, Horvath AR, Jansen R, Jones G, Oosterhuis W, et al. Defining analytical performance specifications: Consensus Statement from the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2015;53:833–5.10.1515/cclm-2015-0067Search in Google Scholar PubMed
5. Fraser CG, Petersen PH. Desirable standards for laboratory tests if they are to fulfill medical needs. Clin Chem 1993;39:1447–53; discussion 53–5.10.1093/clinchem/39.7.1447Search in Google Scholar
6. Statland BE, Winkel P, Killingsworth LM. Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects. Clin Chem 1976;22:1635–8.10.1093/clinchem/22.10.1635Search in Google Scholar
7. Liappis N, Fucks R, Reimnitz P. Intra-individual variation of total protein, transferin, haptoglobin, acid alfa 1-glycoprotein, alfa2-macroglobulin, properdin factor B, C3-complement, C4-complement, IgA, IgG, IgM, alfa1-antitrypsin and caeruloplasmin in the fasting serum of healthy males. Artzl Lab 1986;32:286–92.Search in Google Scholar
8. Ford RP, Mitchell PE, Fraser CG. Desirable performance characteristics and clinical utility of immunoglobulins and light-chain assays derived from data on biological variation. Clin Chem 1988;89:458–68.10.1093/clinchem/34.9.1726Search in Google Scholar
9. Bartlett WA, Braga F, Carobene A, Coskun A, Prusa R, Fernandez-Calle P, et al. A checklist for critical appraisal of studies of biological variation. Clin Chem Lab Med 2015;53:879–85.10.1515/cclm-2014-1127Search in Google Scholar PubMed
10. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409–37.10.3109/10408368909106595Search in Google Scholar PubMed
11. Roraas T, Petersen PH, Sandberg S. Confidence intervals and power calculations for within-person biological variation: effect of analytical imprecision, number of replicates, number of samples, and number of individuals. Clin Chem 2012;58:1306–13.10.1373/clinchem.2012.187781Search in Google Scholar PubMed
12. Hansen CT, Munster AM, Nielsen L, Pedersen P, Abildgaard N. Clinical and preclinical validation of the serum free light chain assay: identification of the critical difference for optimized clinical use. Eur J Haematol 2012;89:458–68.10.1111/ejh.12013Search in Google Scholar PubMed
13. Braga F, Infusino I, Dolci A, Panteghini M. Biological variation of free light chains in serum. Clin Chim Acta 2013;415:10–1.10.1016/j.cca.2012.09.008Search in Google Scholar PubMed
14. Katzmann JA, Snyder MR, Rajkumar SV, Kyle RA, Therneau TM, Benson JT, et al. Long-term biological variation of serum protein electrophoresis M-spike, urine M-spike, and monoclonal serum free light chain quantification: implications for monitoring monoclonal gammopathies. Clin Chem 2011;57:1687–92.10.1373/clinchem.2011.171314Search in Google Scholar PubMed PubMed Central
©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
Articles in the same Issue
- Frontmatter
- Editorial
- Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
- Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
- Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
- Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
- Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
- The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
- Serum and Urine Protein Electrophoresis and Immunofixation Testing
- Challenges of measuring monoclonal proteins in serum
- Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
- Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
- Moving towards harmonized reporting of serum and urine protein electrophoresis
- Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
- Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
- New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
- Serum Free Light Chain Methods and Controversies
- Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
- Measurement of free light chains with assays based on monoclonal antibodies
- Measurement of free light chains – pros and cons of current methods
- Is accuracy of serum free light chain measurement achievable?
- Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
- A patient with AL amyloidosis with negative free light chain results
- Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
- Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
- New Laboratory Assays and Challenges
- Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
- Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
- Free light chains and heavy/light chains in monitoring POEMS patients
- Monitoring free light chains in serum using mass spectrometry
- Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
- Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
- Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
- Letter to the Editor
- Discrepancy between FLC assays: only a problem of quantification?
