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Objectives To evaluate the real-world performance and reference intervals of the Binding Site Freelite serum free light chain (SFLC) assay (Thermo Fisher Scientific), a global standard for diagnosis, prognostication, and response assessment for monoclonal gammopathies. Methods An informatics-based approach was used to retrospectively evaluate concordance between SFLC and the orthogonal Sebia HYDRASYS immunofixation assay results in a large clinical data set consecutively reported between 2010 and 2020. Results Among patients with monoclonal-negative results by both SFLC and Sebia HYDRASYS immunofixation assays, 25% (1226/5057) had κ/λ ratios (KLRs) outside the manufacturer-defined and International Myeloma Working Group–cited normal reference interval of 0.26 to 1.65. These results were consistent over the study period and were not affected by sex, age, impaired kidney function, or assay antisera lot variation. Assay drift, in addition to other potential factors, affected the KLR distribution. Using International Statistical Classification of Diseases (ICD) codes, kidney function data, and the central 95% of KLR values generated on the Optilite platform (Thermo Fisher Scientific), we derived a new reference interval of 0.67 to 2.13, reducing the KLR false-positive rate to 8%. However, normal KLR persisted among 16% (14/85) of samples with free λ chains by immunofixation, warranting caution during interpretation. Conclusions Our analysis indicated that revision of Freelite SFLC reference intervals improves assay interpretation and should prompt reconsideration of Freelite reference intervals worldwide. [ABSTRACT FROM AUTHOR]

Objectives There is considerable variation in ordering practices for the initial laboratory evaluation of monoclonal gammopathies (MGs) despite clear society guidelines to include serum free light chain (sFLC) testing. We assessed the ability of a clinical decision support (CDS) alert to improve guideline compliance and analyzed its clinical impact. Methods We designed and deployed a targeted CDS alert to educate and prompt providers to order an sFLC assay when ordering serum protein electrophoresis (SPEP) testing. Results The alert was highly effective at increasing the co-ordering of SPEP and sFLC testing. Preimplementation, 62.8% of all SPEP evaluations included sFLC testing, while nearly 90% of evaluations included an sFLC assay postimplementation. In patients with no prior sFLC testing, analysis of sFLC orders prompted by the alert led to the determination that 28.9% (800/2,769) of these patients had an abnormal κ/λ ratio. In 452 of these patients, the sFLC assay provided the only laboratory evidence of a monoclonal protein. Moreover, within this population, there were numerous instances of new diagnoses of multiple myeloma and other MGs. Conclusions The CDS alert increased compliance with society guidelines and improved the diagnostic evaluation of patients with suspected MGs. [ABSTRACT FROM AUTHOR]

Objectives: Monoclonal immunoglobulins (M-proteins) that migrate in the β region on serum protein electrophoresis (SPEP) are often cloaked by this region's normal constituents. The present study interrogates the utility of using both quantitative and qualitative alterations in β-region bands for detection of β-migrating M-proteins.Methods: Consecutive SPEP cases analyzed by capillary electrophoresis were searched to identify the initial workup on 1,841 patients with increased total β regions, suspicious β-region findings resulting in reflex immunofixation (IFE), or immunosubtraction (ISUB). To augment quantitative information, separate β1 and β2 measurements were established and retrospectively used to evaluate their sensitivity for M-protein detection.Results: We identified M-proteins in 205 (11.1%) cases, including immunoglobulin A (IgA) (54%), IgG (24%), IgM (13%), and free light chain (9%) isotypes. Of the 15 cases flagged by separate β1 and β2 measurements that were not identified by total β-region measurement, 1 progressed to myeloma. Of the 56 β-migrating M-proteins identified by qualitative features but without increase in any of the β-region measurements, 1 progressed to myeloma.Conclusions: A combination of separate measurements for β1 and β2 regions together with detection of β-region distortions increase sensitivity for identifying β-migrating M-proteins via reflex IFE or ISUB. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of a provider ordering alert to improve laboratory efficiency and reduce costs.Methods: We conducted a retrospective study to assess the use of an institutional reflex panel for monoclonal gammopathy evaluation. We then created a clinical decision support (CDS) alert to educate and encourage providers to change their less-efficient orders to the reflex panel.Results: Our retrospective analysis demonstrated that an institutional reflex panel could be safely substituted for a less-efficient and higher-cost panel. The implemented CDS alert resulted in 79% of providers changing their high-cost order panel to an order panel based on the reflex algorithm.Conclusions: The validated decision support alert demonstrated high levels of provider acceptance and directly led to operational and cost savings within the laboratory. Furthermore, these studies highlight the value of laboratory involvement with CDS efforts to provide agile and targeted provider ordering assistance. [ABSTRACT FROM AUTHOR]

Objectives: Free light chain (FLC) measurement gained a lot of interest for diagnostic workup of monoclonal gammopathy.Methods: We evaluated the performance of turbidimetric polyclonal Freelite (The Binding Site, Birmingham, UK) assays on Cobas 6000 (Roche Diagnostics, Rotkreuz, Switzerland) and nephelometric monoclonal N Latex (Siemens Healthcare Diagnostics, Marburg, Germany) assays on BN ProSpec (Dade Behring, Deerfield, IL) vs established nephelometric Freelite assays on BN ProSpec.Results: Analytical performance was acceptable. Method comparison (n = 118) showed significant proportional FLC differences for N Latex assays. However, good correlation and clinical concordance were shown. Recovery study in the low concentration range demonstrated consistent over- and underrecovery for Freelite reagents, hampering future research on prognostic value of suppressed noninvolved FLC. Antigen excess detection was successful for κ FLC in three-fourths of cases with Freelite reagents and in all cases with N Latex reagents. However, the latter resulted in underestimated κ FLC concentrations.Conclusions: FLC analysis requires continuous awareness of analytical limitations. Monitoring of disease response requires FLC analysis on the same platform using the same reagents. [ABSTRACT FROM AUTHOR]

Objectives: Serum free light chain assay is a recommended screening test for monoclonal gammopathies. Anecdotal observations indicated a high rate of false-positive abnormal κ/λ ratios. This study was undertaken to ascertain the magnitude of the false-positive rate and factors contributing to the error rate.Methods: Results of serum protein electrophoresis, serum free light chains, and related tests, usually done for investigation of suspected monoclonal gammopathy, were reviewed retrospectively for 270 patients and 297 observations.Results: Using the conventional κ/λ ratio, 36.4% of the ratios were abnormal, in the absence of monoclonal gammopathy. When the renal κ/λ ratio was used, the rate of abnormal κ/λ ratios was 30.1%. In patients with a γ-globulin concentration of 1.6 g/dL or more, the usual κ/λ ratio was abnormal in 54.8% of the patients. Urine protein electrophoresis was used in 53 (19.6%) instances, whereas bone marrow examination was done in 65 (24.1%) cases.Conclusions: Usual κ/λ ratio was abnormal in 36.4% of the observations in patients without evidence of monoclonal gammopathy, and an abnormal κ/λ ratio should not be used as the sole indicator for diagnosis of neoplastic proliferation of the lympho-plasmacytic system. Hypergammaglobulinemia is associated with a higher rate of false-positive abnormal κ/λ ratios. Examination of urine for monoclonal immunoglobulins may be underused, and recommendations by some to use serum free light chain assay in place of, rather than as an adjunct to, urine electrophoresis are not warranted. [ABSTRACT FROM AUTHOR]