Usefulness of serum free light chain testing in the handling of monoclonal gammapathies
Diagnosis, prognosis and monitoring
Keywords:
IMMUNOGLOBULIN LIGHT CHAINS, PARAPROTEINEMIAS, MULTIPLE MYELOMA, AMYLOIDOSISAbstract
The serum free light chain testing quantifies levels of free κ and λ. There are three main indications for the measurement of free light chains in the handling of patients with multiple myeloma and associated diseases. First, within the context of diagnosis, they provide the most sensitive pattern for screening together with serum protein electrophoresis and immunifixation electrophoresis, resulting in it not being necessary to perform 24-hour urine collection. Second, basal values of free light chains have proved their prognostic value for most monoclonal gammapathies. Third, serum free light chain testing enables a quantitative and sensitive monitoring in patients with an oligosecretory presentation of the disease, including AL amyloidosis, and in almost 70% of patients who were historically considered to be non-secretory. This review aims to update the information on the application of this testing.
References
(1) Katzmann JA, Kyle RA, Benson J, Larson DR, Snyder MR, Lust JA, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem 2009 Aug; 55(8):1517-22.
(2) Bradwell AR. Serum free light chain analysis. 6th edition. 2010. Capítulo 3, 10-17. Capítulo 4, 18-35.
(3) Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 2006; 52(9):1743-8.
(4) Solomon A. Light chains of human immunoglobulins. Methods Enzymol 1985; 116:101-21.
(5) 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(8):2162-74.
(6) Russo LM, Bakris GL, Comper WD. Renal handling of albumin: a critical review of basic concepts and perspective. Am J Kidney Dis 2002; 39(5):899-919.
(7) Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 2009; 30(3):105-11.
(8) Bence Jones H. Papers ON CHEMICAL PATHOLOGY: prefaced by the Gulstonian Lectures, read at the Royal College of Physicians, 1846. Lancet 1847; 50(1247):88-92.
(9) Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, Drew R. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47(4):673-80.
(10) Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin. Chem 2002 Sep;48(9):1437-44.
(11) Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007; 100(10):635-40.
(12) Drayson MT. Using single protein biomarkers to predict health and disease in diverse patient populations: a new role for assessment of immunoglobulin free light chains. Mayo Clin Proc 2012; 87(6):505-7.
(13) Lindstedt G, Lundberg PA. Loss of tubular proteinuria pattern during urine concentration with a commercial membrane filter cell (Minicon® B-15 system). Clin Chim Acta 1974; 56(1):125-6.
(14) Piehler AP, Gulbrandsen N, Kierulf P, Urdal P. Quantitation of serum free light chains in combination with protein electrophoresis and clinical information for diagnosing multiple myeloma in a general hospital population. Clin Chem 2008; 54(11):1823-30.
(15) Holding S, Spradbery D, Hoole R, Wilmot R, Shields ML, Levoguer AM, et al. Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies. Clin Chem Lab Med 2011; 49(1):83-8.
(16) Robson EJD, Taylor J, Beardsmorre C, Basu S, Mead G, Lovatt T. Utility of serum free light chain analysis when screening for lymphoproliferative disorders. Lab Med 2009; 40:325-9.
(17) Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol 2008; 9:11.
(18) Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23(2):215-24.
(19) Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc 2006; 81(12):1575-8.
(20) Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106(3):812-7.
(21) Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem 2009; 55(3):499-504.
(22) Kumar S, Fonseca R, Dispenzieri A, Katzmann JA, Kyle RA, Clark R, et al. High Incidence of IgH Translocations in Monoclonal Gammopathies with Abnormal Free Light Chain Levels. ASH Annual Meeting Abstracts 2006; 108(11):3514.
(23) Dispenzieri A, Lacy MQ, Katzmann JA, Rajkumar SV, Abraham RS, Hayman SR, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107(8):3378-83.
(24) van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 2007; 110(3):827-32.
(25) Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006; 354(13):1362-9.
(26) Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance. Br. J. Haematol 2006; 134(6):573-89.
(27) Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356(25):2582-90.
(28) Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111(2):785-9.
(29) Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010; 24(6):1121-7.
(30) Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 2013; 27(4):941–6.
(31) Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008; 22(10):1933-7.
(32) Kyrtsonis M, Maltezas D, Tzenou T, Koulieris E, Bradwell AR. Staging Systems and Prognostic Factors as a Guide to Therapeutic Decisions in Multiple Myeloma. Semin Hematol 2009; 46(2):110-7.
(33) International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121(5):749-57.
(34) Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, 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(1):78-84.
(35) Kumar S, Dispenzieri A, Katzmann JA, Larson DR, Colby CL, Lacy MQ, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 2010; 116(24):5126-9.
(36) Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia 2006; 20(9):1467-73.
(37) Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, 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(4):319-28.
(38) Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, 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(36): 4541-9.
(39) Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97(9):2900-2.
(40) Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. International Kidney and Monoclonal Gammopathy Research Group. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 2011; 8(1):43-51.
(2) Bradwell AR. Serum free light chain analysis. 6th edition. 2010. Capítulo 3, 10-17. Capítulo 4, 18-35.
(3) Hill PG, Forsyth JM, Rai B, Mayne S. Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 2006; 52(9):1743-8.
(4) Solomon A. Light chains of human immunoglobulins. Methods Enzymol 1985; 116:101-21.
(5) 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(8):2162-74.
(6) Russo LM, Bakris GL, Comper WD. Renal handling of albumin: a critical review of basic concepts and perspective. Am J Kidney Dis 2002; 39(5):899-919.
(7) Katzmann JA. Screening panels for monoclonal gammopathies: time to change. Clin Biochem Rev 2009; 30(3):105-11.
(8) Bence Jones H. Papers ON CHEMICAL PATHOLOGY: prefaced by the Gulstonian Lectures, read at the Royal College of Physicians, 1846. Lancet 1847; 50(1247):88-92.
(9) Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, Drew R. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47(4):673-80.
(10) Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin. Chem 2002 Sep;48(9):1437-44.
(11) Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. QJM 2007; 100(10):635-40.
(12) Drayson MT. Using single protein biomarkers to predict health and disease in diverse patient populations: a new role for assessment of immunoglobulin free light chains. Mayo Clin Proc 2012; 87(6):505-7.
(13) Lindstedt G, Lundberg PA. Loss of tubular proteinuria pattern during urine concentration with a commercial membrane filter cell (Minicon® B-15 system). Clin Chim Acta 1974; 56(1):125-6.
(14) Piehler AP, Gulbrandsen N, Kierulf P, Urdal P. Quantitation of serum free light chains in combination with protein electrophoresis and clinical information for diagnosing multiple myeloma in a general hospital population. Clin Chem 2008; 54(11):1823-30.
(15) Holding S, Spradbery D, Hoole R, Wilmot R, Shields ML, Levoguer AM, et al. Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies. Clin Chem Lab Med 2011; 49(1):83-8.
(16) Robson EJD, Taylor J, Beardsmorre C, Basu S, Mead G, Lovatt T. Utility of serum free light chain analysis when screening for lymphoproliferative disorders. Lab Med 2009; 40:325-9.
(17) Hutchison CA, Plant T, Drayson M, Cockwell P, Kountouri M, Basnayake K, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrol 2008; 9:11.
(18) Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009; 23(2):215-24.
(19) Katzmann JA, Dispenzieri A, Kyle RA, Snyder MR, Plevak MF, Larson DR, et al. Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc 2006; 81(12):1575-8.
(20) Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106(3):812-7.
(21) Palladini G, Russo P, Bosoni T, Verga L, Sarais G, Lavatelli F, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem 2009; 55(3):499-504.
(22) Kumar S, Fonseca R, Dispenzieri A, Katzmann JA, Kyle RA, Clark R, et al. High Incidence of IgH Translocations in Monoclonal Gammopathies with Abnormal Free Light Chain Levels. ASH Annual Meeting Abstracts 2006; 108(11):3514.
(23) Dispenzieri A, Lacy MQ, Katzmann JA, Rajkumar SV, Abraham RS, Hayman SR, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood 2006; 107(8):3378-83.
(24) van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, et al. High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 2007; 110(3):827-32.
(25) Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006; 354(13):1362-9.
(26) Kyle RA, Rajkumar SV. Monoclonal gammopathy of undetermined significance. Br. J. Haematol 2006; 134(6):573-89.
(27) Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356(25):2582-90.
(28) Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111(2):785-9.
(29) Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 2010; 24(6):1121-7.
(30) Larsen JT, Kumar SK, Dispenzieri A, Kyle RA, Katzmann JA, Rajkumar SV. Serum free light chain ratio as a biomarker for high-risk smoldering multiple myeloma. Leukemia 2013; 27(4):941–6.
(31) Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, et al. Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 2008; 22(10):1933-7.
(32) Kyrtsonis M, Maltezas D, Tzenou T, Koulieris E, Bradwell AR. Staging Systems and Prognostic Factors as a Guide to Therapeutic Decisions in Multiple Myeloma. Semin Hematol 2009; 46(2):110-7.
(33) International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121(5):749-57.
(34) Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, 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(1):78-84.
(35) Kumar S, Dispenzieri A, Katzmann JA, Larson DR, Colby CL, Lacy MQ, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 2010; 116(24):5126-9.
(36) Durie BG, Harousseau JL, Miguel JS, Bladé J, Barlogie B, Anderson K, et al; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia 2006; 20(9):1467-73.
(37) Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, 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(4):319-28.
(38) Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, 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(36): 4541-9.
(39) Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001; 97(9):2900-2.
(40) Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. International Kidney and Monoclonal Gammopathy Research Group. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 2011; 8(1):43-51.
Downloads
Published
2014-03-31
How to Cite
1.
Delgado MF. Usefulness of serum free light chain testing in the handling of monoclonal gammapathies: Diagnosis, prognosis and monitoring. Rev. Méd. Urug. [Internet]. 2014 Mar. 31 [cited 2024 Dec. 4];30(1):65-7. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/261
Issue
Section
Review or Update and Updates
