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Serum Free Light Chain Measurement
Measurement of immunoglobulin free light chains in serum has recently become possible as an alternative to the analysis of Bence Jones proteins in urine. These tests are used as an aid in the diagnosis and monitoring of multiple myeloma and related disorders. There are two types of immunoglobulin light chain produced in humans, designated by the Greek letters kappa (&kappa;) and lambda (&lambda;). Comparing the ratio of kappa / lambda free light chains in the serum of an individual with that measured in a number of subjects known to be disease-free, indicates whether the individual might have a plasma cell tumour such as multiple myeloma or AL amyloidosis.

Serum free light chain assays have been utilised in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma  and AL amyloidosis. This is primarily because of the re-absorption of free light chains in the kidneys, creating a “threshold” of light chain production which must be exceeded before measurable quantities overflow into the urine. While there are a number of publications indicating that serum free light chain analysis is preferable to urine analysis at diagnosis   there is currently no consensus on whether urine tests for monitoring should be replaced .

A series of studies, principally from the Mayo Clinic, have indicated that patients with an abnormal free kappa / free lambda ratio have an increased risk of progression to active myeloma from precursor conditions including Monoclonal Gammopathy of Undetermined Significance (MGUS) Smoldering Myeloma and solitary plasmacytoma of the bone. Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma  and chronic lymphocytic leukaemia.

Guidelines
The International Myeloma Working Group have recently published guidelines making recommendations of when serum free light chain analysis should be used in the management of multiple myeloma :

Diagnosis
The serum free light chain assay in combination with serum protein electrophoresis and serum immunofixation electrophoresis is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL amyloidosis which requires all the serum tests as well as 24h immunofixation electrophoresis.

Prognosis
The serum free light chain assay should be measured at diagnosis for all patients with MGUS, smoldering or active multiple myeloma. Solitary plasmacytoma and AL amyloidosis.

Monitoring
Serial FLC ascertainment should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease. It should also be done in all patients who have achieved a complete response to determine whether they have attained a stringent complete response.

Other guidelines for the use of serum free light chain measurement in the management of AL amyloidosis plasmacytoma and the comparison of treatment responses in clinical trials have also been published.

Technical/clinical reviews of serum free light chain assays have recently been written by Pratt and Jagannath

Patient Information
Information about serum free light chain assays from a patient perspective, is available from the Myeloma Foundation and Myeloma UK