Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma

Kyrtsonis, Marie‐Christine; Vassilakopoulos, Theodoros P.; Kafasi, Nikolitsa; Sachanas, Sotirios; Τζένου, Τατιάνα; Papadogiannis, Argiroula; Galanis, Zacharoula; Kalpadakis, Christina; Dimou, Maria; Kyriakou, Elias; Angelopoulou, Maria K.; Dimopoulou, Maria; Siakantaris, Marina P.; Dimitriadou, Evangelia; Kokoris, Styliani I.; Panayiotidis, Panayiotis; Pangalis, Gerassimos A.

doi:10.1111/j.1365-2141.2007.06561.x

Cited by 109 publications

(81 citation statements)

References 12 publications

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“…9,12,29,32 Kyrtsonis et al 32 found that in 94 MM patients rFLC was prognostic (Figure 3a). Median baseline rFLC was 3.6 in k-MM patients and 0.02 in l-MM.…”

Section: Multiple Myelomamentioning

confidence: 94%

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International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

Dispenzieri

Kyle

Merlini³

et al. 2008

Leukemia

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506

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“…9,12,29,32 Kyrtsonis et al 32 found that in 94 MM patients rFLC was prognostic (Figure 3a). Median baseline rFLC was 3.6 in k-MM patients and 0.02 in l-MM.…”

Section: Multiple Myelomamentioning

confidence: 94%

“…'High rFLC' for patients with clonal kappa or lambda disease was 3.6 and 0.02, respectively. (Kyrtsonis MC et al 32 Prognostic value of serum-free light chain ratio at diagnosis in multiple myeloma. Br J Haematol.…”

Section: Multiple Myelomamentioning

confidence: 99%

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

Dispenzieri

Kyle

Merlini³

et al. 2008

Leukemia

666

506

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“…The serum FLC ratio at diagnosis is prognostic in multiple myeloma (Kyrtsonis et al, 2007) and high serum levels of FLC associated with a rapid reduction in response to therapy defines an aggressive myeloma subtype with a poor prognosis (van Rhee et al, 2007). In contrast a retrospective study of patients with intact immunoglobulin myeloma in the UK MRC trials did not show any correlation between FLC levels at diagnosis and survival .…”

Section: Prognostic and Clinical Correlations Of Serum Flc In Multiplmentioning

confidence: 99%

The evolving use of serum free light chain assays in haematology

Pratt

2008

Br J Haematol

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SummaryOver the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2–4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100–150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non‐secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non‐secretory and oligo‐secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of λ and κ free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.

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“…Although the SPEP is used for clinical management of these patients, serum FLC measurements also play a valuable role. Serum FLC at diagnosis is felt to be an independent prognostic indicator, with high levels being associated with poorer prognosis, particularly when the levels drop rapidly in response to treatment [11,12]. Serum FLC are also used to monitor for disease progression and response to treatment in nearly all myeloma patients.…”

Section: Clinical Applicationsmentioning

confidence: 99%

Serum free light chain analysis

2010

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In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as j and k ''free'' LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol. 85:787-790, 2010. V V C 2010 Wiley-Liss, Inc. BackgroundHematologic malignancies frequently result in the production of monoclonal immunoglobulin. Detection of both intact immunoglobulin and immunoglobulin free light chains (FLC) in the urine and blood has proven to be valuable in the diagnosis, prognosis, and monitoring of treatment of these diseases. One particularly useful property of serum FLC is their short half-life in the blood (j, 2-4 hrs; k, 3-6 hrs) in comparison to intact immunoglobulin (21 days), which provides an opportunity for real-time monitoring of disease progression and response to treatment.For well over a century, testing for the presence of Bence Jones (BJ) protein in the urine was considered to be the gold standard to assess the clonally abnormal levels of immunoglobulin FLC. This technique can detect FLC down to the range of 10-40 mg/L; however, it can be challenging to obtain an accurate 24 hr urine collection, which is necessary for the test [1]. Moreover, due to the high resorptive capabilities of the proximal tubules of the kidney or reduced renal function, patients with low levels of FLC in the serum may not have detectable amounts in the urine [2]. Quantitative alterations of serum immunoglobulins (Igs) may result from polyclonal or monoclonal disorders. The combination of serum protein electrophoresis (SPEP), immunofixation (IFE), and densitometric analysis permits characterization and quantitation of the monoclonal immunoglobulin; however, the sensitivity of SPEP to detect FLC is poor, with a lower limit of sensitivity of 500-2,000 mg/L. Although the IFE does improve sensitivity for the detection of FLC (lower limit of sensitivity 150-500 mg/L), it is a more time-intensive assay and does not allow for quantification. Technical Aspects, Performance, and LimitationsThe development of an accurate and reproducible serum assay to determine j and k FLC concentration with high sensitivity has been a major challenge. A significant barrier to the development of the test is the fact that the unique epitope that is a marker of FLC is ''hidden'' or concealed in the conformational structure of an intact Ig. This precluded the development of a tool such as a specific antibody to detect the ''hidden epitope'' of FLC. This barrier was overcome in 2001 by Bradwell and coworkers [3], who dissociated the FLC from heavy chains and then raised polyclonal antibodies to detect the unique epitopes on j and k LC. T...

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Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma

Cited by 109 publications

References 12 publications

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders

The evolving use of serum free light chain assays in haematology

Serum free light chain analysis

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