scholarly journals Comparison of two serum free light chain assays for the diagnosis of primary plasma cell malignant proliferative disease

2019 ◽  
Vol 2 (4) ◽  
pp. e113 ◽  
Author(s):  
Yang Yang ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Zhen Cai
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Proliferative Disease

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

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.

Serum Free Light Chain Responses after High-Dose Intravenous Melphalan and Autologous Stem Cell Transplantation for AL (Primary) Amyloidosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 942-942
Author(s):  
Vaishali Sanchorawala ◽  
Daniel G. Wright ◽  
Barbarajean Magnani ◽  
Martha Skinner ◽  
David C. Seldin
Keyword(s):  
Stem Cell ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Serum Free ◽  
Hematologic Response ◽  
Serum Free Light Chain

Abstract AL amyloidosis is caused by a clonal plasma cell dyscrasia and characterized by widespread, progressive deposition of amyloid fibrils derived from monoclonal Ig light chains, leading to multisystem organ failure and death. Aggressive treatment of AL amyloidosis with high-dose melphalan followed by autologous stem cell transplant (HDM/SCT) can induce hematologic and clinical remissions and extend survival. Several approaches have been used to define hematologic responses of plasma cell dyscrasias underlying AL amyloidosis following HDM/SCT and other forms of treatment. The definition of a hematologic complete response (CR) that we have used requires that there be no evidence of a persistent monoclonal gammopathy by immunofixation electrophoresis (IFE) of serum and urine proteins, or of persistent plasmacytosis or plasma cell clonality in a bone marrow biopsy by immunohistochemistry. Others have defined hematologic response as a ≥ 50% reduction in free light chain (FLC) measurements. Hematologic responses by both criteria correlate with survival and clinical improvement following HDM/SCT. We have carried out a retrospective analysis of HDM/SCT treatment outcomes for patients with AL amyloidosis to determine the extent to which hematologic CR, by our standard criteria, correlates with FLC response. Serum free light chain concentrations (FLC) were measured by a sensitive nephelometric immunoassay in 67 patients with AL amyloidosis before and after treatment with HDM/SCT. After treatment with HDM/SCT, 27 patients (40%) achieved a CR by standard criteria. Of these 27 patients, 63% (n=17) demonstrated normalization of FLC levels and an improvement of ≥50% in FLC occurred in 100%. Of the 40 patients who did not achieve a CR, 25% (n=10) experienced normalization of FLC levels, and an improvement of ≥50% occurred in 78% (n=31), while only 5 patients (13%) experienced no significant change in FLC. The average improvement in FLC was 94% for patients who achieved a CR by standard criteria and 72% for those who did not (p=0.0001, t-test). Thus, HDM/SCT was found to induce improvements in FLC levels of ≥50% in the vast majority of AL amyloidosis patients treated with HDM/SCT (87%, or 58/67). These data indicate that a decrease in FLC of ≥50% is a substantially less stringent indicator of hematologic response than is CR, as defined by standard criteria. Nonetheless, these measures of hematologic response are complementary, since decreases in FLC can be detected earlier following treatment than changes in IFE and marrow studies required to determine CR.

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