Screening and Diagnosis of Monoclonal Gammopathies: An International Survey of Laboratory Practice

Context.— Serum tests used for the screening and diagnosis of monoclonal gammopathies include serum protein electrophoresis (SPE; agarose gel or capillary zone), immunofixation (IFE) and immunosubtraction capillary electrophoresis, serum free light chains, quantitative immunoglobulins, and heavy/light–chain combinations. Urine protein electrophoresis and urine IFE may also be used to identify Bence-Jones proteinuria. Objective.— To assess current laboratory practice for monoclonal gammopathy testing. Design.— In April 2016, a voluntary questionnaire was distributed to 923 laboratories participating in a protein electrophoresis proficiency testing survey. Results.— Seven hundred seventy-four laboratories from 38 countries and regions completed the questionnaire (83.9% response rate; 774 of 923). The majority of participants (68.6%; 520 of 758) used agarose gel electrophoresis as their SPE method, whereas 31.4% (238 of 758) used capillary zone electrophoresis. The most common test approaches used in screening were SPE with reflex to IFE/immunosubtraction capillary electrophoresis (39.3%; 299 of 760); SPE only (19.1%; 145 of 760); SPE and IFE or immunosubtraction capillary electrophoresis (13.9%; 106 of 760); and SPE with IFE, serum free light chain, and quantitative immunoglobulins (11.8%; 90 of 760). Only 39.8% (305 of 767) of laboratories offered panel testing for ordering convenience. Although SPE was used by most laboratories in diagnosing new cases of myeloma, when laboratories reported the primary test used to follow patients with monoclonal gammopathy, only 55.7% (403 of 724) chose SPE, with the next most common selections being IFE (18.9%; 137 of 724), serum free light chain (11.7%; 85 of 724), and immunosubtraction capillary electrophoresis (2.1%; 15 of 724). Conclusions.— Ordering and testing practices for the screening and diagnosis of monoclonal gammopathy vary widely across laboratories. Improving utilization management and report content, as well as recognition and development of laboratory-directed testing guidelines, may serve to enhance the clinical value of testing.

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A comparison between high resolution serum protein electrophoresis and screening immunofixation for the detection of monoclonal gammopathies in serum

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0266 ◽

2018 ◽

Vol 56 (2) ◽

pp. 256-263 ◽

Cited By ~ 5

Author(s):

Joel Smith ◽

Geoffrey Raines ◽

Hans-Gerhard Schneider

Keyword(s):

High Resolution ◽

Sensitivity And Specificity ◽

Serum Protein ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Protein Electrophoresis ◽

Serum Protein Electrophoresis ◽

Agarose Gel ◽

Serum Free ◽

Monoclonal Gammopathies

Abstract Background: There are a variety of initial laboratory tests or combinations of tests that can be performed when a monoclonal gammopathy is suspected including serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation (IFE) and serum free light chain assays. Some groups have recently used simplified “screening” IFE methods for the detection of monoclonal gammopathies leveraging the greater sensitivity of IFE over SPEP alone to improve the detection of monoclonal gammopathies. These screening techniques have been predominantly evaluated against lower resolution agarose gel electrophoresis techniques. Methods: In this study we evaluated the diagnostic performance of the combined κ and λ light chain screening immunofixation (CLIF) in comparison to serum protein electrophoresis on a high-resolution (Sebia Hydragel 15 HR) agarose gel system. Each gel was interpreted by three adjudicators. A total of 156 patient samples were analysed. Adjudicated diagnoses based on the screening techniques were compared against the results of high resolution serum protein electrophoresis and high resolution standard immunofixation performed during routine laboratory operation. Where standard immunofixation was not performed a combination of a review of medical records, serum free light chains, UPEP and bone marrow aspirate and trephine and subsequent standard immunofixation and protein electrophoresis results where available were used to confirm the absence of a monoclonal gammopathy. Results: In this cohort a total of 65 (41%) patients had a paraprotein confirmed by standard immunofixation. HR SPEP had a sensitivity and specificity of 95% and 85%, respectively, while CLIF had a sensitivity and specificity of 88% and 97%, respectively. Conclusions: Overall we found that high-resolution gel serum protein electrophoresis using a Sebia Hydragel 15 HR system was more sensitive than a screening immunofixation method (CLIF) for the detection of paraproteins in patient serum in this patient cohort. The drawback of the greater sensitivity of HR SPEP was a higher false positive rate requiring an increased utilisation of follow up immunofixation electrophoresis.

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Elimination of the Need for Urine Studies during Diagnostic Studies of Monoclonal Gammopathies by the Combined Use of Serum Immunofixation and Serum Free Light Chain Assays.

Blood ◽

10.1182/blood.v108.11.5011.5011 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5011-5011

Author(s):

Jerry A. Katzmann ◽

Angela Dispenzieri ◽

Robert Kyle ◽

Melissa R. Snyder ◽

Mathew F. Plevak ◽

...

Keyword(s):

Light Chain ◽

Monoclonal Gammopathy ◽

Diagnostic Algorithm ◽

Protein Electrophoresis ◽

Free Light Chain ◽

Urine Protein ◽

Serum Free ◽

Monoclonal Gammopathies ◽

Serum Free Light Chain ◽

Monoclonal Proteins

Abstract Due to the diagnostic sensitivity of serum free light chain quantitation for monoclonal light chain diseases, it has been suggested that urine assays no longer need be performed as part of the diagnostic algorithm for monoclonal proteins. We reviewed our experience to determine the relative diagnostic contribution of urine assays. Methods: Patients with a monoclonal gammopathy and monoclonal urinary protein at initial diagnosis who also had a serum immunofixation and serum free light chain quantitation within 30 days of diagnosis were identified (n = 428). The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. Results: The patients in this cohort had diagnoses of multiple myeloma, primary amyloid, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. By definition of the cohort, all 428 had a monoclonal urine protein. 86% had an abnormal serum free light chain K/L ratio, 81% had an abnormal serum protein electrophoresis, and 94% had an abnormal serum immunofixation. In only 2 patients, however, were all 3 serum assays normal. Both of these were patients with monoclonal gammopathy of undetermined significance (idiopathic Bence Jones proteinuria). Conclusion: Discontinuation of urine studies and reliance on a diagnostic algorithm using solely serum studies (protein electrophoresis, immunofixation, and free light chain quantitation), missed 2 of the 428 monoclonal gammopathies (0.5 %) with urinary monoclonal proteins, and these 2 cases required no medical intervention.

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A monoclonal gammopathy precedes multiple myeloma in most patients

Blood ◽

10.1182/blood-2008-12-195008 ◽

2009 ◽

Vol 113 (22) ◽

pp. 5418-5422 ◽

Cited By ~ 331

Author(s):

Brendan M. Weiss ◽

Jude Abadie ◽

Pramvir Verma ◽

Robin S. Howard ◽

W. Michael Kuehl

Keyword(s):

Multiple Myeloma ◽

Serum Protein ◽

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Protein Electrophoresis ◽

Serum Free ◽

Serum Free Light Chain ◽

Chain Analysis ◽

Immunofixation Electrophoresis

Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.

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