An Analysis of M-protein in Plasma cell Dyscrasia Patients Identifies that IgG Lambda Subtype is More Commonly Associated with Normal Serum Free Light Chain (SFLC) Ratio

2021 ◽  
Author(s):  
Manish K. Singh ◽  
Vinita Paswan ◽  
Sonal Dwivedi ◽  
Ruchi Gupta ◽  
Khaliqur Rahman ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Normal Serum ◽  
Free Light Chain ◽  
M Protein ◽  
Plasma Cell Dyscrasia ◽  
Serum Free ◽  
Serum Free Light Chain

Kidney disease and plasma cell dyscrasias: ambiguous cases solved by serum free light chain dimerization analysis

2019 ◽  
Vol 23 (6) ◽  
pp. 763-772
Author(s):  
Olga Kukuy ◽  
Batia Kaplan ◽  
Sizilia Golderman ◽  
Alexander Volkov ◽  
Adrian Duek ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Plasma Cell Dyscrasias

The relationship between the serum free light chain assay and serum immunofixation electrophoresis, and the definition of concordant and discordant free light chain ratios

Blood ◽  
2009 ◽  
Vol 114 (1) ◽  
pp. 38-39 ◽  
Author(s):  
Seema Singhal ◽  
Eric Vickrey ◽  
Jairam Krishnamurthy ◽  
Veerpal Singh ◽  
Sharon Allen ◽  
...  
Keyword(s):  
Light Chain ◽  
Normal Serum ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Immunofixation Electrophoresis ◽  
Serial Samples ◽  
Definition Of ◽  
The Relationship

Abstract“Stringent” complete remission in myeloma has been defined by a normal serum free light chain ratio (SFLCR) in addition to the standard criteria for CR. 2648 serial samples from 122 IgG or IgA myeloma patients were studied to explore the relationship between SFLCR and serum immunofixation electrophoresis (SIFE). SFLCR was normal in 34% of cases with positive SIFE and abnormal in 66%. SFLCR was normal in 69% of cases with negative SIFE and abnormal in 31%. When evaluated with SIFE as the benchmark, the sensitivity of SFLCR was 66% and specificity was 69%. These findings were unchanged when abnormal SFLCR values were classified as concordant (< 0.26 for λ disease and > 1.65 for κ) or discordant (< 0.26 for κ disease and > 1.65 for λ). Additional studies are required to determine the temporal relationship between SFLCR normalization and paraprotein clearance. Until then, the role of SFLCR in defining response remains controversial.

Comparison of Serum Free Light Chain Levels and 24 Hour Urinary Monoclonal Protein Secretion in Patients with Myeloma: Concordant Changes with Response to Therapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5064-5064 ◽  
Author(s):  
Shaji Kumar ◽  
S. Vincent Rajkumar ◽  
Matthew Plevak ◽  
Robert A. Kyle ◽  
Jerry A. Katzmann ◽  
...  
Keyword(s):  
Light Chain ◽  
Protein Level ◽  
Free Light Chain ◽  
Response To Therapy ◽  
M Protein ◽  
Serum Free ◽  
Protein Levels ◽  
Serum Free Light Chain ◽  
Data Points ◽  
Over Time

Abstract Background: The measurement of monoclonal (M) protein in the serum and urine is critical for response assessment and disease evaluation in patients with multiple myeloma (MM). The serum free light chain (FLC) assay offers a new and sensitive method of assessing response to therapy. An important question that has not been adequately addressed is the correlation between 24 hour urine M protein levels and serum FLC measurements, and the extent to which response to therapy estimated using the FLC assay correlates with that assessed using the 24 hour urine M protein level. Methods: A total of 2194 sets of data, with simultaneous UPEP and serum FLC measurement, were studied. These included 752 unique patients, with individual patients having 1–23 paired assessments over time. FLC estimation was carried out using the serum FLC assay (Freelite; The Binding Site Limited, UK) performed on a Dade-Behring Nephelometer. Based on the established reference range, kappa/lambda FLC ratio &lt;0.26 or &gt;1.65 were defined as abnormal indicating the presence of monoclonal lambda and kappa FLC, respectively. The monoclonal light chain isotype was considered the involved FLC isotype, and the opposite light chain type as the uninvolved FLC type. The Urine M protein by UPEP was compared to the serum levels of the involved light chain using Spearman Rank Correlation. For comparisons in individual patients over time, those with at least 10 measurements each were studied. Results: The median involved FLC level in patients with an undetectable urine M protein was 2.3 mg/dl compared to 32.2 mg/dL among those with a detectable urine M protein (P&lt;0.001). Among the 1676 points with an abnormal FLC ratio, only 75% had an M protein detected in the urine, P &lt; 0.001. Conversely, among patients with a positive urine M-protein, 91% had an abnormal FLC ratio. When all the 2194 data points were considered together, there was a significant correlation between the urine M protein level and the FLC levels (FLC level calculated as the difference between involved and uninvolved levels), rho=0.763, P &lt; 0.001. The correlation did not change when patients with a serum creatinine of over 2.5 were excluded. The correlation between FLC levels and urinary M protein can be affected by several factors such as renal function that will differ across patients. Therefore, we examined whether the correlation between the two variables is stronger when the variations introduced by inter-patient differences in the relationship between the two variables are eliminated. In order to do this, we studied individual patients on whom multiple data points over time were available. One patient who had the maximum number of paired assessments (23 pairs) of serum FLC level and urinary M protein; the correlation between the two variables over time was highly significant, rho 0.981, p&lt;0.001. Similarly 26 other patients who had measurable urine M protein levels in whom 10 nor more paired observations over time were available, also showed significant correlations, rho, range 0.726–0.981, p&lt;0.01. Conclusion: There is a significant correlation between urine M-protein and serum free light chain across patients and the correlation is stronger in individual patients in whom the effect of inter-patient variation in other confounding factors can be eliminated. These data if confirmed in a clinical trial setting would support the use of serum FLC levels instead of urinary M protein measurements to assess response to therapy.

Heavy/Light Chain Quantification Identifies Clonal Plasma Cell Disease in Patients with AL Amyloidosis and Normal Serum Free Light Chain Ratio

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2956-2956
Author(s):  
Tatiana Prokaeva ◽  
Brian Spencer ◽  
Fangui Sun ◽  
Nathaniel McConnell ◽  
Richard M O'hara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Binding Site ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Al Amyloidosis ◽  
Cell Disease ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Combined Use

Abstract Background: Serum and urine immunofixation electrophoreses (SIFE/UIFE) are routinely used for detection of clonal immunoglobulins (Ig) in AL amyloidosis. Serum free light chain (FLC) assays (Freelite®, The Binding Site Ltd., Birmingham, UK) have significantly improved the management of patients with AL amyloidosis by providing quantitative measure for the detection and monitoring of clonal plasma cell disease. However, up to 20% of patients with AL amyloidosis may have uninformative serum free light chain values. Objective: To assess the quantitative potential of serum Heavy/Light Chain (HLC) pairs (Hevylite®, The Binding Site Ltd., Birmingham, UK) assay in identification of clonal plasma cell disease in AL amyloidosis. Methods: One hundred and ninety-nine untreated patients with AL amyloidosis were included in this study. Patients with multiple myeloma or B cell lymphoproliferative diseases associated AL amyloidosis were excluded. Serum sampleswere obtained at initial evaluation and stored at -20°C. SIFE/UIFE were performed at the time of sample collection. HLC pairs were assessed by the Hevylite® assay. HLC κ/λ normal ratios (HLCR) were: 1.12-3.21 for IgG κ/λ; 0.78-1.94 for IgA κ/λ; and 1.18-2.74 for IgM κ/λ. FLCs were assessed by the Freelite® assay; FLC κ/λ normal ratio (FLCR) was 0.26-1.65. In 103 cases, FLC testing was performed at the time of sample collection; 96 cases were tested at The Binding Site. Vital status of patients was obtained from either medical records or Social Security Death Index. Follow-up ended in June 2014. Results: An abnormal HLCR was found in 74 (37.2%), an abnormal FLCR in 163 (81.9%), and SIFE/UIFE positivity in 187 (94%) of 199 patients with AL amyloidosis. Of 36 patients with a normal FLCR, 23 (63.9%) were noted with an abnormal HLCR compared to 51 (31.3%) patients in an abnormal FLCR group (P = 0.001). In total 186/199 (93.5%) patients with AL amyloidosis had abnormalities in either HLCR or FLCR, compared to 187/199 (94%) of patients who were SIFE/UIFE+ (Table 1). The combined use of both FLCR and HLCR yielded quantifiable information in 93.5% of cases; the use of both tests in combination with SIFE/UIFE identified plasma cell clonality in 100% of patients. Seventy-two cases presented with an abnormal HLCR for a single isotype and 2 in multiple Ig isotypes. In all cases, involved LC type of abnormal HLCR matched LC type identified by SIFE/UIFE. None of 12 cases that were negative on the SIFE/UIFE presented with an abnormal HLCR, however, all showed abnormalities in FLCR. Table 1. Comparative efficiency of FLCR, HLCR and Serum/Urine Immunofixation in AL Amyloidosis patients. SIFE/UIFE+ (n=187) SIFE/UIFE- (n=12) HLCR+/FLCR+ 51 (27.2%) - HLCR+/FLCR- 23 (12.3%) - HLCR-/FLCR+ 100 (53.5%) 12 (100%) HLCR-/FLCR- 13 (7%) - Overall survival was similar in patients with and without abnormal HLCR (Log rank p=0.092; Figure 1), whereas patients with an abnormal FLCR had a significantly inferior overall survival compared to those with a normal FLCR (Log rank p=0.027; Figure 2). Combined use of both HLCR and FLCR demonstrated a trend toward superior overall survival in a group of patients with an abnormal HLCR / normal FLCR (Wilcoxon p=0.037; Log rank p=0.107; Figure 3). Conclusions: The Hevylite® assay provided information in addition to other laboratory tests for clonal plasma cell disease in AL amyloidosis. The combined use of the HLCR and FLCR provided quantifiable information in 93.5% of patients. The use of both assays in combination with SIFE/UIFE detected clonal disease in all patients. HLCR has potential to quantify clonal disease in patients with uninformative FLCR results. An abnormal HLCR was not predictive of overall survival, while an abnormal FLCR was, in this series of patients. Combined use of HLCR and FLCR could be beneficial in prognostication of outcome in AL amyloidosis. Disclosures McConnell: The Binding SIte: Employment. O'hara:The Binding Site: Employment.

Assessment of Serum Free Light Chain Assay for Screening for Plasma Cell Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2563-2563
Author(s):  
David E. Smith ◽  
Jude Abadie ◽  
Daniel Bankson ◽  
Graham Mead
Keyword(s):  
Multiple Myeloma ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Plasma Cell ◽  
Light Chain ◽  
Predictive Value ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Plasma Cell Disorders

Abstract Introduction and Methods: The purpose of this study was to evaluate the serum free light chain (FLC) assay in its ability to improve performance of protocols designed to screen for plasma cell disorders. We measured M-protein levels using serum protein electrophoresis (SPEP) in 312 consecutive patients being screened for plasma cell disorders at the Veterans Administration Medical Center - Puget Sound. The serum kappa and lambda free light chain levels were quantitated using the serum FLC assay in these same patients. The kappa/lambda ratio was calculated using the free kappa and free lambda results from the serum FLC assay. Results: SPEP results indicated the presence of a possible monoclonal gammopathy in 77 of the 312 patients in this study. In this group of 77 patients, a plasma cell disorder was diagnosed in 27 of them. The serum FLC assay showed an abnormal kappa/lambda ratio in 20 of these 77 patients, all 20 of whom were diagnosed with multiple myeloma. In the group of 235 patients with normal SPEP results, 17 were found to have an abnormal kappa/lambda ratio. Of these 17 patients, 15 were diagnosed with multiple myeloma, one with lymphoma, and one with bladder cancer. Conclusions: Because a number of disorders and diseases can increase production of immunoglobulins, there were a significant number of false positives in the SPEP results. At the same time, there were also several false negative SPEP results. The number of both false positives and false negatives was smaller for the serum FLC assay. Further, use of SPEP and the serum FLC assay together resulted in significantly improved sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). (See Table 1.) These results indicate an important role for the serum FLC assay in screening for monoclonal gammopathies. Table 1. Performance of SPEP, sFLC, and both assays in screening for plasma cell disorders SPEP Alone sFLC Alone Both SPEP and sFLC Sensitivity 64% 88% 100% Specificity 81% 98% 99% Positive Predictive Value 35% 88% 89% Negative Predictive Value 94% 98% 100%

scholarly journals Is accuracy of serum free light chain measurement achievable?

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Joannes F.M. Jacobs ◽  
Jillian R. Tate ◽  
Giampaolo Merlini
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Clinical Consequence ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Quantitative Monitoring ◽  
Plasma Cell Disorders ◽  
Prognostic Stratification ◽  
Plasma Cell Dyscrasias

AbstractThe serum free light chain (FLC) assay has proven to be an important complementary test in the management of patients with monoclonal gammopathies. The serum FLC assay has value for patients with plasma cell disorders in the context of screening and diagnosis, prognostic stratification, and quantitative monitoring. Nonetheless, serum FLC measurements have analytical limitations which give rise to differences in FLC reporting depending on which FLC assay and analytical platform is used. As the FLC measurements are incorporated in the International Myeloma Working Group guidelines for the evaluation and management of plasma cell dyscrasias, this may directly affect clinical decisions. As new certified methods for serum FLC assays emerge, the need to harmonise patient FLC results becomes increasingly important. In this opinion paper we provide an overview of the current lack of accuracy and harmonisation in serum FLC measurements. The clinical consequence of non-harmonized FLC measurements is that an individual patient may or may not meet certain diagnostic, prognostic, or response criteria, depending on which FLC assay and platform is used. We further discuss whether standardisation of serum FLC measurements is feasible and provide an overview of the steps needed to be taken towards harmonisation of FLC measurements.

The serum-free light chain assay cannot replace 24-hour urine protein estimation in patients with plasma cell dyscrasias

Blood ◽  
2007 ◽  
Vol 109 (8) ◽  
pp. 3611-3612 ◽  
Author(s):  
Seema Singhal ◽  
Regina Stein ◽  
Eric Vickrey ◽  
Jayesh Mehta
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Urine Protein ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Protein Estimation ◽  
Plasma Cell Dyscrasias
Sign in / Sign up

Export Citation Format

Share Document