A patient with AL amyloidosis with negative free light chain results
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Paolo Milani
und
Giampaolo Merlini
Abstract
The detection and quantification of amyloidogenic monoclonal light chains are necessary for the diagnosis and evaluation of response to treatment in AL amyloidosis. However, the amyloid clone is often small and difficult to detect. We report the case of a 68-year-old man who was referred to our Center in April 2013 after syncope and the identification of left ventricular hypertrophy at echocardiography, suspected for amyloidosis. A commercial agarose gel electrophoresis immunofixation (IFE) did not reveal monoclonal components in serum and urine. The κ serum free light chain (FLC) concentration was 21.5 mg/L, λ 33 mg/L (κ/λ ratio 0.65), NT-proBNP 9074 ng/L (u.r.l. <332 ng/L) and an echocardiogram confirmed characteristic features of amyloidosis. The abdominal fat aspiration was positive and the amyloid typing by immune-electron microscopy revealed λ light chains deposits. A high-resolution (hr) IFE of serum and urine showed a faint monoclonal λ component in the urine. A bone marrow biopsy showed 8% plasma cells (BMPC) and a kappa/lambda light-chain restriction with λ light chain on immunofluorescence. The diagnosis of AL (λ) amyloidosis with cardiac involvement was made. In May 2013, patient was started on cyclophosphamide, bortezomib and dexamethasone. After six cycles, serum and urine hr-IFE were negative, the bone marrow biopsy showed 3% BMPC without light chain restriction by immunofluorescence, and a decrease of NT-proBNP was observed (5802 ng/L).Thus, treatment was discontinued. In this patient the amyloid clone could be detected only by in house hr-IFE of urine and bone marrow examination. The detection of the small dangerous amyloidogenic clone should be pursued with a combination of high-sensitivity techniques, including assessment of BMPC clonality. Studies of novel tools, such as mass spectrometry on serum and next-generation flow cytometry analysis of the bone marrow, for detecting plasma cell clones in AL amyloidosis and other monoclonal light chain-related disorders are warranted.
References
1. Merlini G, Stone MJ. Dangerous small B-cell clones. Blood 2006;108:2520–30.10.1182/blood-2006-03-001164Suche in Google Scholar PubMed
2. Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem 2009;55:499–504.10.1373/clinchem.2008.117143Suche in Google Scholar PubMed
3. Katzmann J, Kyle R, Benson J, Larson D, Snyder M, Lust J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009;55:1517–22.10.1373/clinchem.2009.126664Suche in Google Scholar PubMed PubMed Central
4. de Larrea CF, Verga L, Morbini P, Klersy C, Lavatelli F, Foli A, et al. A practical approach to the diagnosis of systemic amyloidoses. Blood 2015;125:2239–44.10.1182/blood-2014-11-609883Suche in Google Scholar PubMed
5. Brambilla F, Lavatelli F, Di Silvestre D, Valentini V, Rossi R, Palladini G, et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood 2012;119:1844–7.10.1182/blood-2011-07-365510Suche in Google Scholar PubMed
6. Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR 3rd, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 2009;114:4957–9.10.1182/blood-2009-07-230722Suche in Google Scholar PubMed
7. Merlini G, Marciano S, Gasparro C, Zorzoli I, Bosoni T, Moratti R. The Pavia approach to clinical protein analysis. Clin Chem Lab Med 2001;39:1025–8.10.1515/CCLM.2001.167Suche in Google Scholar PubMed
8. Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood 2013;121:5124–30.10.1182/blood-2013-01-453001Suche in Google Scholar PubMed
9. Perfetti V, Vignarelli MC, Anesi E, Garini P, Quaglini S, Ascari E, et al. The degrees of plasma cell clonality and marrow infiltration adversely influence the prognosis of AL amyloidosis patients. Haematologica 1999;84:218–21.Suche in Google Scholar
10. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol 2012;30:4541–9.10.1200/JCO.2011.37.7614Suche in Google Scholar PubMed
©2016 by De Gruyter
Artikel in diesem Heft
- 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?
Artikel in diesem Heft
- 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?
