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2015, Number 2

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Rev Hematol Mex 2015; 16 (2)

Light chains: Total or free? Which ones should be measured

Delgado F

Language: Spanish
References: 34
Page: 143-151
PDF size: 476.26 Kb.


ABSTRACT

Finding the most efficient diagnostic scheme that ensures the highest possible sensitivity and specificity for detection of monoclonal proteins in patients with multiple myeloma may present some controversy. This is the case of immunoassays for the quantification of light chains, which are still generating discussion although clinical endorsements are very strong. There are two types of assays commercially available currently that measure κ and λ light chains in serum. One type measures total (free and bound to heavy chains) light chains. The other type measures only free light chains. The current use of total light chain assay occurs in spite of international warnings that indicate the method is not sensitive enough for routine clinical use. Indeed, samples containing large amounts of free light chains may be completely missed using the total light chain technique. Different studies had compared the sensitivity between methods, both total and free light chain assays, in order to evaluate the clinical impact. The aim of this review article is to clarify some concepts about the foundations of the free light chain assay, distinguishing it from the total light chain assay and to compare the clinical utility of both tests.


REFERENCES

  1. Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 2009;30:105-111.

  2. Dispenzieri A, Kyle R, Merlini G, Miguel JS, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215-224.

  3. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:538-548.

  4. Waldmann TA, Strober W, Mogielnicki RP. The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia. J Clin Invest 1972;51:2162-2174.

  5. Kim J, Hayton WL, Robinson JM, Anderson CL. Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model. Clin Immunol 2007;122:146-155.

  6. Abraham RS, Katzmann JA, Clark RJ, Bradwell AR, et al. Quantitative analysis of serum free light chains. A new marker for the diagnostic evaluation of primary systemic amyloidosis. Am J Clin Pathol 2003;119:274-278.

  7. Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361:489-491.

  8. Drayson M, Tang LX, Drew R, Mead GP, et al. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97:2900-2902.

  9. Lachmann HJ, Gallimore R, Gillmore JD, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 2003;122:78-84.

  10. Clamp JR. Some aspects of the first recorded case of multiple myeloma. Lancet 1967;2:1354-1356.

  11. Bradwell AR, Carr-Smith HD, Mead GP, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673-680.

  12. Laine ST, Soppi ET, Mörsky PJ. Critical evaluation of the serum kappa/lambda light-chain ratio in the detection of M proteins. Clin Chim Acta 1992;207:143-149.

  13. Jones RG, Aguzzi F, Bienvenu J, Gasparro C, et al. Use of immunoglobulin heavy-chain and light-chain measurements in a multicenter trial to investigate monoclonal components: II. Classification by use of computer-based algorithms. Clin Chem 1991;37:1922-1926.

  14. Mariën G, Oris E, Bradwell AR, Blanckaert N, Bossuyt X. Detection of monoclonal proteins in sera by capillary zone electrophoresis and free light chain measurements. Clin Chem 2002;48:1600-1601.

  15. Kyle RA. Sequence of testing for monoclonal gammopathies. Arch Pathol Lab Med 1999;123:114-118.

  16. Gertz MA, Comenzo R, Falk RH, Fernand JP, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol 2005;79:319-328.

  17. Durie BG, Harousseau JL, Miguel JS, Bladé J, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473.

  18. Zamora-Ortiz G, Velázquez-Sánchez-de-Cima S, Hernández- Reyes J, Martagón-Herrera NA, et al. Poor performance of the total kappa/lambda light chain quantification in the diagnosis and follow-up of patients with multiple myeloma. Rev Invest Clin 2014;66:314-318.

  19. Delgado F, Kuus K. Comparison of free kappa and lambda light chain immunoassays and total (bound and free) kappa and lambda light chain immunoassays. Rev Invest Clin 2014;66:473-474.

  20. Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, et al. Serum free light chains for monitoring multiple myeloma. Br J Haematol 2004;126:348-354.

  21. Drayson MT, Morgan GJ, Jackson GH, et al. Prospective study of serum FLC and other M-protein assays: when and how to measure response? Clin Lymphoma Myeloma 2009;9:56.

  22. Hutchison C, Plant T, Drayson M, Cockwell P, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with acute renal failure. BMC Nephrol 2008:9:1-18.

  23. Palladini G, Russo P, Bosoni T, Sarais G, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem2009;55:499-504.

  24. Nowrousian MR, Brandhorst D, Sammet C, Kellert M, et al. Serum free light chain analysis and urine immunofixation electrophoresis in patients with multiple myeloma. Clin Cancer Res 2005;11:8706-8714.

  25. Hassoun H, Reich L, Klimek VM, Dhodapkar M, et al. Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma. Br J Haematol 2006;132:155-161.

  26. Alyanakian MA, Abbas A, Delarue R, Arnulf B, Aucouturier P. 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 Hematol 2004;75:246-248.

  27. Wechalekar AD, Hawkins PN, Gillmore JD. Perspectives in treatment of AL amyloidosis. Br J Haematol 2008;140:365-377.

  28. Palladini G, Dispenzieri A, Gertz MA, Kumar S, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol 2012;30:4541-4549.

  29. Fantl D. Guía hematológica de mieloma múltiple-Sociedad Argentina de Hematología. Sociedad Argentina de Hematología 2013:289-316.

  30. Hungria VT, Crusoe EQ, Quero AA, Sampaio M, et al. Guidelines on the diagnosis and management of multiple myeloma treatment: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular Project guidelines: Associação Médica Brasileira-2012. Rev Bras Hematol Hemoter 2013;35:201-217.

  31. Manual de manejo de mieloma múltiple. Sociedad Venezolana de Hematología 2013:1-158.

  32. Guía de práctica clínica. Diagnóstico y tratamiento del mieloma múltiple. México: Secretaría de Salud,2010:1-80.

  33. Gómez-Almaguer D, Cano-Castellanos Raúl CL, Garcés-Ruiz Oscar M, Gómez-Almaguer David, et al. Guías mexicanas de diagnóstico y recomendaciones terapéuticas para mieloma múltiple (2009). Revista de Hematología 2010;11:40-62.

  34. Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007;100:635-640.




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