Limitations of Free Light Chain Assays caused by the Matrix Effect

2020 ◽  
Vol 5 (2) ◽  
pp. 311-319
Author(s):  
Christopher W Farnsworth ◽  
Nicole M Logsdon ◽  
Jennifer E Hayes ◽  
Rehan Rais ◽  
Maria A Willrich ◽  
...  
Keyword(s):  
Binding Site ◽  
Light Chain ◽  
Matrix Effect ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Follow Up Studies ◽  
The Matrix ◽  
The Impact

Abstract Background Serum free light chain (FLC) assays are used clinically to measure the concentration of κ and λ FLC in patients with suspected or diagnosed plasma cell proliferative disorders. Previous studies have demonstrated a loss of linearity in low concentration ranges of these assays. We hypothesized that this result could be caused by a matrix effect. Methods Recovery studies were performed for κ and λ FLC in both serum and saline using the Freelite assay (Binding Site) on a Cobas c502 system (Roche). Samples were analyzed either at the recommended dilution or undiluted. Follow-up studies were performed in varying matrices ranging from 0% to 100% saline. Retrospective patient data were analyzed to assess the impact on reported κ FLC, λ FLC, and κ/λ ratio. Results FLC in a serum matrix demonstrated underrecovery relative to samples diluted in saline for both κ and λ FLC. Of 255 patient samples with λ FLC measured undiluted (λ FLC <6.0 mg/L), an unexpected gap was observed in patient results between 2.0 and 6.0 mg/L. In addition, 23 patients measured serially with λ FLC between 2.0 and 6.0 mg/L demonstrated dramatic changes in κ/λ ratio, with no changes in κ FLC, likely because of the matrix effect. Conclusions The κ and λ Freelite assays exhibit a matrix effect when samples are tested undiluted, which has the potential to affect the κ/λ ratio. Consequently, our laboratory has stopped reporting λ FLC <6.0 mg/L.

The Addition of sFLCR Improves ISS Prognostication in Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1490-1490 ◽  
Author(s):  
Marie-Christine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Nikolitsa Kafasi ◽  
Dimitris Maltezas ◽  
Athanasios Anagnostopoulos ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Light Chain ◽  
Free Light Chain ◽  
Newly Diagnosed ◽  
Prognostic Information ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Poor Outcomes ◽  
Chain Type

Abstract We have recently shown that serum free light chain ratio (sFLCR) provides independent prognostic information in patients with newly diagnosed MM (Kyrtsonis et al, Br J Haematol, 137: 240–243, 2007). The aim of the present study was to extend our previous observations in a multicenter setting and to investigate the potential additive effect of sFLCR to the ISS system, in determining the prognosis of patients with MM. We analyzed 214 newly diagnosed MM patients (125 kappa-, 89 lambda-). Serum free light chain levels were measured in sera drawn at diagnosis, using a latex-enhanced immunoassay (The Binding Site, Birmingham, UK). Then, the sFLCR was calculated, accordingly as kappa/lambda or lambda/kappa, depending on the monoclonal light chain type of the patient. Based on our previous study “high” sFLCR was defined as ratios ≥3.57 and ≥45.09 for kappa- and lambda- MM respectively. The median age of the patients was 68 years (33–92), 51% were males, 28%, 30%, and 42% had Durie-Salmon stages I, II, and III, 14% creatinine >2 mg/dl, and 13% had Bence-Jones MM. ISS stage was 1, 2, or 3 in 33%, 33%, and 34% of the patients, 48% had CRP ≥4 mg/l, 18% elevated LDH, 31% hemoglobin <10 g/dl, 32% albumin <3.5 g/dl, and 51% bone marrow infiltration ≥50%. The median sFLCR was 6.00 in the 125 kappa-MM, and 46.43 in the 89 lambda-MM patients. With a median follow-up of 16 months (1–105), 88 MM patients with “low” sFLCR had a 3-year disease specific survival (DSS) of 93±4% vs. 63±6% for 126 patients with “high” sFLCR. The corresponding 5-year DSS rates were 83±7% vs. 43±10% (p=0.0001). In multivariate analysis, “high” sFLCR provided prognostic information independent of the value of ISS, as further reflected by the data presented in the table. LDH levels further contributed in the discrimination of prognosis in multivariate analysis: A subgroup of 19 patients (9% of total) with “high” sFLCR plus ISS=3 plus elevated LDH had a 0% projected DSS at 19 months. sFLCR and the previously described models remained predictive of the outcome, if only patients requiring treatment at diagnosis were analyzed. In conclusion, baseline sFLCR appears to be an easily determined, powerful, independent and very promising novel prognostic factor for survival in patients with newly diagnosed MM. Establishment of the optimal cutoff and prospective validation is needed. Its addition to ISS and LDH can identify subgroups of patients with excellent or very poor outcomes. DSS According to the Combined sFLCR and ISS System Patient Subgroup Pts (#,%) 3-yr DSS (%) 5-yr DSS (%) p “Low” sFLCR and ISS <3 61 (29) 95 90 Either “High” sFLCR or ISS=3 96 (46) 82 56 <0.0001 “High” sFLCR and ISS=3 50 (24) 37 24

Serum Free Light Chain and Serum Heavy / Light Chain Ratios Are Independently Prognostic in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4880-4880
Author(s):  
Efstathios Koulieris ◽  
Stephen Harding ◽  
Marie-Christine Kyrtsonis ◽  
Caroline Bradley ◽  
Mark T Drayson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Binding Site ◽  
Prognostic Marker ◽  
Light Chain ◽  
Prognostic Indicator ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Site Group ◽  
Serum Igg

Abstract Abstract 4880 Serum free light chain ratios (FLCr) are important prognostic markers in B cell malignancies and their measurement has recently been included in multiple myeloma (MM) international guidelines. In contrast, serum IgG and IgA concentrations are not prognostic in MM. Novel immunoassays have been developed which target the specific conformational, junctional epitopes between the heavy and light chains of the immunoglobulin making it possible to measure Ig'kappa and Ig'lambda and produce an Ig'kappa /Ig'lambda ratio. Here we describe the use of FLCr and heavy/light chain ratios (HLCr) to predict survival in MM patients. Archived sera from a historic MRC and a more recent Velcade, Adriamycin, dexamethazone (PAD) MM trail were utilised and the data combined using each study as a categorical variable. 85 MRC and 73 PAD samples were analysed retrospectively using serum free light chain and serum heavy / light chain nephelometric assays (The Binding Site Group). Kaplan Meier curves and Cox regression analysis were constructed comparing the upper quartile to the lower three quartiles for involved intact immunoglobulin, FLC, HLC and FLC + HLC. All analysis was completed using SPSS v14.0. FLCr and HLCr values were not correlated (Pearson's = -0.037 p=0.66). There was no significant difference in survival when comparing the lower three quartiles and upper quartile of the involved intact immunoglobulin (Hazard Ratio [HR]=1.16: p=0.585). However, comparison of the upper quartile to the lower three quartiles did reveal significant differences in survival times for FLCr (HR=2.16: p=0.003), HLCr (HR=1.94: p=0.01) and FLCr+HLCr (HR=3.34: p=0.001). Intact immunoglobulin concentration was not prognostic in this study in keeping with current international prognostic guidelines. As with previously published data, FLCr was a prognostic indicator in MM (van Rhee 2007, Kyrtsonis 2007). It is likely FLCr is more predictive of outcome than the concentration of tumour FLC production (data not shown) because it includes a measure of immunoparesis. HLCr was an independent prognostic indicator of survival in this study. HLCr measurement may be superior to intact immunoglobulin in predicting outcomes because: 1) Changes in haematocrit and plasma volume in MM can cause Ig to change by more than 50% regardless of tumour production. 2) Serum IgG is susceptible to variable clearance rates (related to saturation of the FcRn receptor for IgG). 3) Ig measurements using serum protein electrophoresis or nephelometry include all or some of the non-tumour Immunoglobulins and may be non-linear. The summated FLCr and HLCr is a stronger prognostic marker than either measurement independently. This maybe because, as shown by Ayliffe (2007) myeloma cells can produce intact immunoglobulin, FLC or both. Therefore, in patients with very low intact immunoglobulin production and high FLC production, FLCr is likely to be the most prognostic marker and visa versa for patients with low FLC production. Conclusion In this combined study FLCr, HLCr and FLCr + HLCr were found to be predictive of overall survival in MM patients. Larger studies comparing HLCr and FLCr with B2M and Albumin as used in the international staging system are needed. Disclosures Harding: The Binding Site Group Ltd: Employment. Bradley:The Binding Site Group Ltd: Employment. Bradwell:The Binding Site Group Ltd: Shareholder.

Intact Immunoglobulin or Fragments Thereof Can Be Detected in Urine in a Proportion of Patients with Multiple Myeloma and Are Associated with Reduced Survival At Presentation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1828-1828
Author(s):  
Heinz Ludwig ◽  
Philip Young ◽  
Dejan Milosavljevic ◽  
Niklas Zojer ◽  
Wolfgang Hübl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Binding Site ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Glomerular Injury ◽  
Female Ratio ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Abstract 1828 Introduction: Intact immunoglobulin or fragments thereof (intact/fragmented Ig) can be found in the urine due to nephrotic injury or the preferential scavenging of albumin by the renal FcRn receptor leading to immunoglobulin catabolism. Until now the occurrence, frequency and clinical impact of this phenomenon has not been assessed in patients with multiple myeloma (MM). Here we determine the incidence of intact/fragmented Ig in urine and evaluate its prognostic relevance. Patients and Methods: 94 patients with MM, median age 70 years old (range 41–87) with a male / female ratio 28/66, ISS stage I (48), stage II (23), stage III (28), 69 IgG (43 IgGk/26 IgGl) and 25 IgA (15 IgAk/7 IgAl) were enrolled. Serum free light chain concentrations (sFLC) were measured using commercially available immunoassays (Freelite™, The Binding Site, Birmingham, UK) and compared to electrophoresis results (Hydrasys, Sebia, Paris, France). Overall survival was estimated by the product limiting method of Kaplan-Meyer and survival was compared by the log rank test. Results: Overall, sFLC ratios had a greater sensitivity than urine immunofixation (uIFE) for the detection of monoclonal light chains 86/94 vs. 46/94. In 13/46 (28%) uIFE positive patients intact immunoglobulins or significant fragments (intact/fragmented Ig) thereof were detected, 12 IgG, (12/69, 17%) and 1 IgA (1/25, 4%). Three of these patients had normal urine protein concentrations (<250mg/L) and 2/13 patients had glomerular injury identified by increased levels of albumin excretion. There was no difference in creatinine levels between patients with or without intact/fragmented Ig (p=0.673). Analysis of overall survival in patients stratified at presentation according to uIFE results, namely the presence of intact/fragmented Ig, abnormal serum free light chain ratio-, and negative uIFE results revealed significantly shorter overall survival for the intact/fragmented Ig group (median OS: 34.5 vs. 66.0, vs. 80.6 months, respectively, p< 0.048) (figure 1). Discussion: Our findings confirm the superiority of the serum free light chain assay for detection of monoclonal free light chains as compared to urine immunofixation. However, the serum free light chain assay is inadequate for detection of intact/fragmented Ig in urine. The most important finding presented here is the observation that intact and/or fragment immunoglobulin is present in a substantial number of patients with MM. This phenomenon is mainly restricted to IgG isotypes. There are two possible explanations for these findings: first, the presence of glomerular injury, but this phenomenon (increased albumin leakage) was only seen in two patients and hence is unlikely to account for this observation. The second explanation relies upon disruption of the FcRn receptor function in immunoglobulin scavenging. This receptor will preferentially scavenge albumin in the renal setting, but dysfunction may lead to increased immunoglobulin catabolism and the presence of intact and/or fragmented Ig (Sarav, JASN, 20: 1941–1952, 2009). The results may reflect a hitherto unidentified subtle renal dysfunction. In line with this notion overall survival in our patients intact/fragmented Ig was found to be significantly shorter. Conclusion: We observed an unexpected high incidence of intact/fragmented Ig in the urine of our patients with MM. Patients with urinary excretion of intact/fragmented immunoglobulin had significantly shorter survival. These findings should be validated in further studies. Disclosures: Young: Binding Site: Employment. Harding:Binding Site: Employment.

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.

Serum Free Kappa to Free Lambda Ratios as an Adjunct to Serum Protein Electrophoresis for the Detection of Monoclonal Proteins in the Serum.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4856-4856
Author(s):  
Arthur R. Bradwell ◽  
Jean Garbincius ◽  
Earle W. Holmes
Keyword(s):  
Serum Protein ◽  
Light Chain ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Serum Protein Electrophoresis ◽  
Serum Free ◽  
Monoclonal Protein ◽  
Serum Free Light Chain ◽  
Monoclonal Proteins

Abstract Serum free light chain measurements have been shown to be useful in the diagnosis and monitoring of patients with monoclonal gammopathies. The present study was undertaken to evaluate the effect of adding the measurement of serum free light chain kappa to lambda ratios to the serum protein electrophoresis evaluation that we typically use as an initial screen for the detection of monoclonal proteins. We retrospectively tested 347 consecutive samples from individuals who had no previous history of plasma cell dyscrasia and had not previously had a serum or urine electrophoresis or immunofixation electrophoresis test at our institution. The quantitative serum protein electrophoresis test that was ordered was performed using Hydragel Beta 1- Beta 2 gels and Hydrasis instrument (Sebia, Inc., Norcross, GA). The protein content of the electrophoresis zones were quantitated by scanning densitometry and the electrophoresis pattern of each sample was qualitatively examined for abnormal bands and suspicious findings by a single, experienced observer. Serum free light chain concentrations and the serum free light chain kappa to lambda ratios were determined using the Freelite Human Kappa and Lambda Kits (The Binding Site Ltd, Birmingham, UK) and the Immage analyzer (Beckman Coulter Inc., Brea, CA). The serum free light chain kappa to lambda ratios were outside the reference interval (0.25 to1.65) in 23 of the samples. Ten abnormal ratios were observed among a group of 57 samples that had either positive or suspicious qualitative evaluations for the presence of a restriction or that demonstrated hypo-gammaglobulinemia. Both abnormalities led to recommendations for follow-up testing, which confirmed the presence of a monoclonal protein in 21 of the samples. Six abnormal ratios were observed among a group of 159 specimens that had quantitative abnormalities in albumin or one or more of globulin fractions (hypo-gammaglobulinemia excepted) and normal qualitative evaluations. Seven abnormal ratios were observed among a group of 131 samples that had normal quantitative results and normal qualitative evaluations. Follow-up testing is not usually recommended for serum protein electrophoresis results like those in the latter two groups. We found that the addition of the serum free light chain kappa to lambda ratio to the serum protein electrophoresis test increased the number of abnormal screens that would have required further clinical and/or laboratory evaluation by 23%(i.e. from 57 to 70). Given the high specificity of the serum free light chain kappa to lambda ratio for monoclonal light chains, the additional 13 abnormal samples identified by this test are expected to have a high likelihood of harboring a monoclonal protein that would have otherwise eluded detection. Pending a definitive prospective study, we estimate that the addition of a serum free light chain kappa to lambda ratio to the serum protein electrophoresis screen would increase the rate of detection of serum monoclonal proteins by as much as 1.6-fold.

Serum Free Light Chain Assessment in 311 Patients with Gammopathy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4750-4750
Author(s):  
Fernanda Trigo ◽  
Cristina Guimaraes ◽  
Abilia Bodas ◽  
Armando Teixeira-Pinto ◽  
Jose E. Guimaraes
Keyword(s):  
Multiple Myeloma ◽  
Sensitivity And Specificity ◽  
Light Chain ◽  
Final Diagnosis ◽  
Reference Intervals ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Total Light

Abstract Serum free light chain (FLC) levels are a useful multiple myeloma (MM) marker and a indicator of tumour burden both for diagnosis and follow up purposes. A total of 311 patient samples were assayed in our laboratory for FLC and the kappa/lambda (κ/λ) chain ratio was calculated and compared with the classical methods for characterization of gammopathy (immunofixation, IMF, immunoglobulin levels and total light chain levels and respective ratio). Ig (A, G, M) and total κ and λ chain levels were assayed by nephlometry (Dade-Behring BNII). Immunofixation was performed in a Hydrasys (Sebia) setting. FLC assay was done using Binding Site reagents (Dade-Behring). Statistical analysis was performed by SPSS® for Windows v. 15. Concordance between IMF results and free κ/λ chain ratio was calculated. Sensitivity and specificity of the free κ/λ chain ratio in the identification of positive and negative IMF were also determined. Reference intervals used for free κ/λ and total κ/λ chain ratios were [0.26; 1.65] and [1.35; 2.65], respectively. Out of 311 patients with gammopathy studied, 235 had absence of monoclonality as defined by the immunoelectrophoretic profile. Inclusively, only 51% of the 53 patients with suspected MM and 66% of the 41 patients with a diagnosis of MGUS were IMF positive. Sensitivity and specificity of total κ/λ chain ratio for identification of positive or negative IMF were respectively 70% and 91% with a global concordance of 86%. In 215 (70%) patients, IMF and free κ/λ chain ratio were in agreement. However, 74 (32%) of IMF negative patients had abnormal free κ/λ chain ratio: 18% had a final diagnosis of chronic renal failure, 13% of CLL or NHL, 9% of MGUS, 7% of MM and 3% of amyloidosis; the remainder 50% were diagnosed as having a disease other than lymphoplasmacytic disorder. These results stress the value of free light chain determination in the diagnosis and follow up of gammopathies and its usefulness as a marker for multiple myeloma and associated monoclonal gammopathies.

Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2900-2902 ◽  
Author(s):  
Mark Drayson ◽  
Lian X. Tang ◽  
Roger Drew ◽  
Graham P. Mead ◽  
Hugh Carr-Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Activity ◽  
Light Chain ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Using sensitive, automated immunoassays, increased concentrations of either κ or λ free light chains (and abnormal κ/λ ratios) were detected in the sera of 19 of 28 patients with nonsecretory multiple myeloma. Four other patients had suppression of one or both light chains, and the remaining 5 sera had normal or raised free light-chain concentrations with substantially normal κ/λ ratios. Six of the patients with an elevated single free light chain, who were studied during follow-up, had changes in disease activity that were reflected by the changes in free light-chain concentrations. It is concluded that quantification of free light chains in serum should prove useful for the diagnosis and monitoring of many patients with nonsecretory myeloma.

Elevated, combined serum free light chain levels and increased mortality: a 5-year follow-up, UK study

2012 ◽  
Vol 65 (11) ◽  
pp. 1036-1042 ◽  
Author(s):  
Seetharam Anandram ◽  
Lakhvir Kaur Assi ◽  
Tracy Lovatt ◽  
Jayne Parkes ◽  
Joanne Taylor ◽  
...  
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Kaplan Meier ◽  
Risk Of Mortality ◽  
Patients At Risk ◽  
Risk Patients ◽  
Almost All

AimsAbnormal serum free light chain (FLC) ratios are diagnostically important in almost all plasma cell disorders. However, absolute increases in polyclonal FLC levels are often discarded as inconsequential. Here we report an association between increased combined polyclonal FLC (cFLC: FLCκ plus FLCλ) concentrations and mortality.Methods723 patients sent for 30 routine haematological assessments were enrolled. Patients with a confirmed monoclonal gammopathy were removed. The remaining 527 patients were followed up for up to 4.5 years. Statistical analysis was performed using SPSS (V.19).ResultsDuring follow-up, there were 99 deaths (18.8%). Kaplan-Meier survival analysis revealed 29% of these deaths occurred within the first 100 days (N=29). Multivariate analysis identified only cFLC >65 mg/l, albumin <33 g/l and  estimated glomerular filtration rate <30 ml/min/1.73 m2 to be independently associated with mortality within 100 days and 4.5 years with, cFLC having the highest HR of 7.1. A simple risk stratification model based only on albumin and cFLC identified 86% mortality within 100 days and 62% over 4.5 years.ConclusionsElevated cFLC is significantly associated with increased mortality and with albumin can be used to identify patients at risk of mortality at 4.5 years with high-risk patients detected within 100 days.

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