Diagnostic reference range of κ/λ free light chain ratio to screen for Bence Jones proteinuria is not significantly influenced by GFR

2015 ◽  
Vol 96 (5) ◽  
pp. 527-531
Author(s):  
Yvonne Schmidt-Hieltjes ◽  
Clemens Elshof ◽  
Lian Roovers ◽  
Janneke Ruinemans-Koerts
Keyword(s):  
Light Chain ◽  
Reference Range ◽  
Free Light Chain ◽  
Bence Jones Proteinuria

Comparaison of Serum Free Light Chain Measurement with Classical Methods for the Evaluation of Patients with Immunoproliferative Diseases under Treatment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5123-5123
Author(s):  
Florence Cattan ◽  
Richard Delarue ◽  
Fadi Fakhouri ◽  
Aicha Abbas ◽  
Bertrand Arnulf ◽  
...  
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Routine Activity ◽  
Light Chains ◽  
Primary Amyloidosis ◽  
Moderate Increase ◽  
Light Chain Deposition Disease ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Bence Jones Proteinuria

Abstract Background: Therapeutic evaluation of immunoproliferative diseases requires precise quantification of the monoclonal (M) component. It currently relies on standardized methods such as serum electrophoresis or measurement of Bence-Jones proteinuria. In some cases, absence or very low level of serum and/or urinary M component hinders precise evaluation by conventional techniques. Serum quantification of free light chains (FLC) by nephelemetry, developed by Dr A. Bradwell and colleagues, has been shown to be relevant in such situations. Our study was designed to assess the usefulness of this method in the routine activity of a single institution. Patients and methods: forty-eight consecutive patients referred to the hematology and/or nephrology department of our institution were evaluated. These patients presented with immunoproliferative diseases including multiple myeloma (n = 38) among which 20 light chain myelomas, primary amyloidosis (n = 8) and light chain deposition disease (LCDD) (n = 2). Standard electrophoresis, measurement of Bence-Jones proteinuria and serum FLC measurement (FreeliteTM, The Binding Site, Birmingham, UK) were performed in all patients with a minimum of three consecutive evaluation during treatment. The three methods were compared to determine their respective clinical benefits for clinicians. Results: Nine patients with light chain myeloma and all patients with amyloidosis and LCDD presented with proteinuria under 0.5 g/d. In addition, 4 patients with myeloma had a serum M component below 5 g/L. Thus, difficult evaluation may be expected in 48 % of patients. Two patients failed to be evaluated by the FLC method because of normal concentrations of kappa and lambda light chains and normal kappa to lambda ratio. Thirty five percent of patients (17/48) were easily evaluated by the classical methods and no substantial additional information was obtained using serum free light chain measurement. In 21/48 (44%) of patients, for whom classical method failed to recognize any M component in serum or urine, serum FLC measurement proved very useful. For the remaining 8 patients with proteinuria < 0.5 g/d or serum M component < 5 g/l in whom evaluation with classical methods is difficult, determination of serum FLC demonstrated higher sensitivity to variations during treatment. Results were not influenced by the type of treatment. A cost-effective study shown a moderate increase in cost with FreeliteTM compared to classical methods. Conclusion: We studied the interest of a new serum FLC measurement method in the management of patients with immunoproliferative diseases. As expected, it appears very high in patients in whom classical methods are not suitable, a common feature in patients with light chain myeloma, amyloidosis and LCDD. By contrast, patients assessable with classical techniques do not benefit from this new method. We conclude that this method can be very useful, albeit only in a minority of patients with hardly assessable immunoproliferative diseases. It is our belief that serum FLC quantification should be restricted to this subgroup of patients.

Prevalence of Abnormal Serum Free Light Chain Ratio in Monoclonal Gammopathies at Presentation and Sensitivity for Bence Jones Proteinuria.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1495-1495 ◽  
Author(s):  
Stephen Holding ◽  
Dorothy Spradbery ◽  
Robin Hoole ◽  
Rachel Wilmot ◽  
Michael L. Shields ◽  
...  
Keyword(s):  
Light Chain ◽  
Prognostic Significance ◽  
Reference Interval ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Royal Infirmary ◽  
Serum Free ◽  
Monoclonal Gammopathies ◽  
Excess Light ◽  
Bence Jones Proteinuria

Abstract Introduction: Recent data suggest that serum monoclonal free light chain ratio (LCR) may have prognostic significance in monoclonal gammopathies. We routinely assay serum free light chains (FLC) in all new patients with a monoclonal gammopathy with the primary aim of identifying patients with a significant level of free light chain. We made a retrospective analysis of these data in order to establish the range of results observed in our patients and to establish a cohort of patients who will be followed up to evaluate the prognostic significance of LCR abnormalities. Aims: To identify the proportion of patients with monoclonal gammopathies that have abnormal serum LCR at presentation. To identify how many patients have abnormal serum LCR but no other evidence of excess light chain production. To establish the sensitivity of serum LCR for the presence of Bence Jones proteinuria. Method and Setting: We analyzed data from a consecutive cohort of 496 patients with a newly identified paraprotein (by serum or urine protein electrophoresis and immunofixation), who had samples referred to the Immunology Department at Hull Royal Infirmary between 05/03/06 and 07/31/07. Serum FLC analysis was performed by a latex-enhanced immunoassay (The Binding Site, Birmingham, UK on a Beckman-Coulter IMMAGE nephelometric analyzer). Serum (SPE) and urine (UPE) protein electrophoresis were perfomed by SEBIA Hydrasys gel system or Capillarys 2 capillary electrophoresis system. Results: Paraproteins were evident by SPE in 98% of patients (488 of 496). In the remaining 8 patients (2%) the paraprotein was only visible by UPE. Serum LCR was outside the standard reference interval (0.26–1.65) in 272 (55%) of all patients and in 124 (36%) of the 343 patients who had no FLC detected by SPE or UPE. Urines were received from 281 (57%) patients and a paraprotein was detected in 151 (54%) of these by UPE. FLC was detected in 126 (83%) of urines containing a paraprotein and in 89 (59%) was the sole paraprotein present in the urine. Of the 126 patients who had FLC detected by UPE, 124 (98%) had serum LCR outside the standard reference interval, and 119 (94%) had serum LCR outside the mean±3.5 sd range (0.18–2.01). The remaining two patients with normal LCR both had IgG-kappa paraproteins with a small free kappa band in the urine. The molecular weight of these free kappa bands has not yet been confirmed by SDS-PAGE electrophoresis and immunoblotting. Conclusions: Raised serum LCR was present in 55% of patients with a paraprotein at diagnosis. 36% of patients with no other evidence of excess light chain production had abnormal LCR. Using the LCR standard reference interval had a sensitivity of 98% for the presence of Bence Jones proteinuria. This high sensitivity of LCR for Bence Jones proteinuria supports the cessation of UPE and its replacement with serum LCR. Our cohort of newly presenting, unselected patients with monoclonal gammopathies will be followed to determine the prognostic value of LCR for these patients.

scholarly journals Free Light Chain Escape in Multiple Myeloma : an Exceptional Phenomenon

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4428-4428 ◽  
Author(s):  
Helene Caillon ◽  
Michel Attal ◽  
Herve Avet-Loiseau ◽  
Cyrille Touzeau ◽  
Philippe Moreau ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Light Chain ◽  
Research Funding ◽  
Progressive Disease ◽  
Free Light Chain ◽  
Bone Lesions ◽  
Measurable Disease ◽  
Bence Jones Proteinuria ◽  
Monoclonal Component

Abstract Background : Free Light Chain (FLC) escape has been described for the first time in 1971 by Hobbs, who reported biochemical relapses of multiple myeloma (MM) with only Bence Jones proteinuria, in patients followed for an intact monoclonal immunoglobulin (Ig) MM. Indeed, FLC escape is defined as an increase of FLC without corresponding increase of the intact monoclonal Ig. In the era of novel-agent based therapy and autologous stem cell transplantation (ASCT), the patterns of disease progression may change, including a potential increased rate of FLC escape. Brioli and al (Blood 2014;123(22):3414-9) reported that 10% of the cases at relapse presented with FLC escape, and that FLC evaluation at relapse could represent an interesting marker of impact from intraclonal heterogeneity on myeloma outcome. We analysed the relapse patterns of patients treated according to the IFM 2009 clinical trial. Methods: Patients treated according to the IFM 2009 clinical trial (Lenalidomide bortezomib dexamethasone RVD + / - ASCT, Attal and al, ASH 2015) were analyzed. In patients presenting with an intact monoclonal Ig at diagnosis, serum and urine electrophoresis + FLC were compared in a central lab at the time of diagnosis and at the time of progression, in order to identify FLC escape. Results: 700 patients with symptomatic de novo MM were enrolled in the IFM DFCI 2009 clinical trial. Among them, 318 had a progressive disease, assessed with a centralized biochemistry analysis and 267 patients of them with an intact monoclonal Ig were included in this study. A vast majority (250 patients, 94%) showed an increase of the initial serum monoclonal component up to 5 g/L or up to 25% from the NADIR (IMWG criteria for progressive disease). 8 patients progressed with new bone lesions or plasmocytoma (3%) without any biological markers of progressive disease... Finally, 9 patients (3%) were identified as FLC escape as they did not exhibit an increased intact monoclonal Ig but they had an increased serum FLC and/or an increased Bence Jones proteinuria. Three of them had a serum and urinary measurable disease on diagnosis and they relapsed with both an increase of FLC and an increase of Bence Jones proteinuria. The six other patients presented at diagnosis only with an urinary measurable disease: 3 of them relapsed with an increase of FLC, without any Bence Jones proteinuria, the three others relapsed both on FLC and urines. Isotype of monoclonal component was IgG (6 patients), IgA (2) or IgD (1); light chain was Kappa for 6 patients and Lambda for the three others. Four patients were treated with RVD alone, and 5 patients with RVD + ASCT. The relapse occurred in a median of 2 years after diagnosis (5 months - 3.5 years). Conclusion: Based on a very large study of patients treated into a phase 3 clinical trial with centralized assessment of response and relapse, we are showing that FLC escape in a very rare phenomenom, observed in 3% of the cases. The low frequency of FLC escape does not lead to a systematic monitoring of intact Ig MM by FLC. Disclosures Attal: amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding; sanofi: Consultancy. Avet-Loiseau:sanofi: Consultancy; janssen: Consultancy; amgen: Consultancy; celgene: Consultancy. Moreau:Takeda: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria.

Free light chain kappa and the polyspecific immune response in MS and CIS – Application of the hyperbolic reference range for most reliable data interpretation

2020 ◽  
Vol 346 ◽  
pp. 577287 ◽  
Author(s):  
Marie Süße ◽  
Hansotto Reiber ◽  
Matthias Grothe ◽  
Astrid Petersmann ◽  
Matthias Nauck ◽  
...  
Keyword(s):  
Immune Response ◽  
Light Chain ◽  
Reference Range ◽  
Data Interpretation ◽  
Reliable Data ◽  
Free Light Chain
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