Summary of Data

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Logarithmic scale plot of absolute free kappa (κ) and free lambda (λ) concentrations in a group of normal patients and those with a variety of B cell dyscrasia. Calculation of the κ/λ ratio distinguishes elevated polyclonal immunoglobulin and renal impairment (κ/λ ratio is normal) from monoclonal gammopathies with an abnormal / ratio e.g. Lambda and Kappa BJ. More

Published data indicate that 100% of patients with Light Chain (Bence Jones) Multiple Myeloma1, 82% of patients with Nonsecretory Multiple Myeloma2, over 98% of patients with AL amyloidosis3 and 96% of Intact Immunoglobulin Multiple Myeloma patients4 have abnormal serum free light chain concentrations. This improvement in disease detection rates, and the superior utility of serum free light chains for disease monitoring, may obviate the need for urine free light chain tests in most patients with monoclonal plasma diseases.

Additionally, the serum free light chain ratio has been identified as a major new independent risk factor for progression of patients with MGUS to multiple myeloma or other related disorders5. *

Serum free light chain assays have been added to the new International uniform response criteria for assessing clinical outcomes in multiple myeloma and are included in an increasing number of guidelines for the diagnosis and management of AL amyloidosis and multiple myeloma.

A recent review by Sundar Jagannath, St Vincent's Comprehensive Cancer Center, New York, looks at the value of these assays in haematology6. General information on the use of serum free light chains is also available in a Clinical Chemistry editorial7 and in Clinical Laboratory News (CLN), June 2006.

* In the USA diagnostic use of this product is restricted to those stated in the product insert

International One Day Conference, September 10th 2004

Applications of serum free light chain tests in Haematology

The latest data on diagnosis and monitoring with Freelite™ was presented to over 150 haematologists, biochemists and immunologists who attended the third UK symposium on applications of free light chain assays.

Eminent speakers included Professor Robert Kyle and Professor Philip Greipp from the Mayo Clinic, USA, Professor Michel Attal, Hôpital de Toulouse, France and Dr Helen Lachmann, UK National Amyloid Reference Centre, Royal Free Hospital, London.

The final session was a Summary and Discussion of a Free Light Chain Consensus Statement. The panel was Robert Kyle, Michel Attal, Philip Greipp, Helen Lachman and Jo Bradwell.

Consensus Statement - Application of Serum Free Light Chain Testing

The following summarises the consensus view for the diagnosis and monitoring of patients with monoclonal gammopathies utilising free light chain immunoassays:

Consensus statement
 Disease For Diagnosis For Monitoring
Nonsecretory MM2 Important Important
AL Amyloidosis3,8,9 Important Important
Light Chain MM1,10 Important Important
Intact immunoglobulin MM4 Important Useful/Important
MGUS5 Important Important
Light Chain Deposition Disease11 Important Important
Waldenstroms macroglobulinaemia Insufficient data Insufficient data
Plasmacytoma Insufficient data Insufficient data
Lymphoma/Leukaemia Insufficient data Insufficient data
Smouldering MM Insufficient data Insufficient data
Choice of statements was - Important, Useful, Minor use, No value, Insufficient data

Feedback from delegates highlighted that:

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References

  1. Arthur R Bradwell, Hugh D Carr-Smith, Graham P Mead, Timothy C Harvey, Mark T Drayson.
    "Serum test for assessment of patients with Bence Jones myeloma"
    Lancet 2003;361:489-491

    Reference: MKG189 Quantity:

  2. Mark Drayson, Liang X. Tang, Roger Drew, Graham P. Mead, Hugh Carr-Smith, and Arthur R. Bradwell.
    "Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma"
    Blood 2001;97:9:2900-2902

    Reference: MKG183 Quantity:

  3. Helen J. Lachmann, Ruth Gallimore, Julian D. Gillmore, Hugh D. Carr-Smith, Arthur R. Bradwell, Mark B. Pepys and Philip N. Hawkins.
    "Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy"
    BJH 2003;122:78-84

    Reference: MKG200 Quantity:

  4. G. P. Mead, H. D. Carr-Smith, M. T. Drayson, G. J. Morgan, J. A. Child and A. R. Bradwell.
    "Serum free light chains for monitoring multiple myeloma"
    BJH 2004;126:348-354

    Reference: MKG228 Quantity:

  5. S.Vincent Rajkumar, Robert A. Kyle, Terry M. Therneau, L. Joseph Melton III, Arthur R. Bradwell, Raynell J. Clark, Dirk R. Larson, Matthew F. Plevak, Angela Dispenzieri, Jerry A. Katzmann.
    "Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance (MGUS)"
    Blood 2005;106;3: 812-817

    Reference: MKG275 Quantity:

  6. Sundar Jagannath
    "Value of Serum Free Light Chain Testing for the Diagnosis and Monitoring of Monoclonal Gammopathies in Hematology."
    Clinical Lymphoma and Myeloma 2007 7(8):518-523

    Reference: MKG405 Quantity:

  7. Arthur R. Bradwell.
    "Serum Free Light Chain Measurements Move to Center Stage"
    Clin Chem 2005;51:5:805-807

    Reference: MKG254 Quantity:

  8. United Kingdom Myeloma Forum on behalf of the British Committee for Standards in Haematology (BCSH).
    "Guidelines on the diagnosis and management of AL amyloidosis"
    BJH 2004;125:681-700

    Reference: MKG227 Quantity:

  9. Roshini S Abraham, Jerry A Katzmann, Raynell J Clark, A R Bradwell, Robert A Kyle, Morie A Gertz.
    "Quantitative Analysis of Serum Free Light Chains"
    American Journal of Clinical Pathology (2003)

    Reference: MKG196 Quantity:

  10. Marie-Alexandra Alyanakian, Aicha Abbas, Richard Delarue, Bertrand Arnulf and Pierre Aucouturier.
    "Free Immunoglobulin Light-Chain Serum Levels in the Follow-up of Patients With Monoclonal Gammopathies: Correlation With 24-hr Urinary Light-Chain Excretion"
    Am J Hematology 2004;75:246-248

    Reference: MKG222 Quantity:

  11. Jerry A. Katzmann, Raynell J. Clark, Roshini S. Abraham, Sandra Bryant, James F. Lymp, Arthur R. Bradwell, and Robert A. Kyle.
    "Serum Reference Intervals And Diagnostic Ranges For Free κ And Free λ Immunoglobulin Light Chains: Relative Sensitivity For Detection Of Monoclonal Light Chains"
    Clin Chem 2002;48:9:1437-1444

    Reference: MKG194 Quantity: