Home Free light chains and heavy/light chains in monitoring POEMS patients
Article
Licensed
Unlicensed Requires Authentication

Free light chains and heavy/light chains in monitoring POEMS patients

  • Sara Altinier EMAIL logo , Kozeta Proko , Martina Zaninotto , Daniela Ciubotaru , Mara Seguso , Mariacristina Varagnolo , Federica Lessi , Chiara Briani , Fausto Adami and Mario Plebani ORCID logo
Published/Copyright: April 12, 2016

Abstract

Background: POEMS syndrome is defined by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. The vascular endothelial growth factor (VEGF) appears to play a key role in the pathogenesis of the syndrome, and its concentrations are deemed to correlate to disease activity. The aim of the present study was to verify whether other biochemical markers including serum free light chains (FLC) and heavy/light chains (HLC) would be of value in monitoring POEMS patients.

Methods: Fifty-three serum samples were collected from seven POEMS patients at diagnosis and during a follow-up period (range 14–56 months). VEGF was measured using an ELISA method, while FLC and HLC concentrations were measured using Binding Site reagents on a BNII (Siemens) nephelometer.

Results: At diagnosis all patients presented high VEGF concentrations, while the κ/λFLC ratio (FLCr) was within the reference range. Four patients had abnormal HLC, HLCκ/HLCλ (HLCr) and FLC values. The relationship between the trend of VEGF and both HLC and FLC during the follow-up was analysed by means of Cohen’s κ coefficient. VEGF and HLC values displayed a significant κ-Cohen (0.537, p=0.002) in all chemotherapy-responder patients while in non-responders it did not. Conversely, in both responders and non-responders, VEGF and FLC values did not attain a significance on κ-Cohen analysis. In three out of four responders HLCr values increased, thus reflecting an improved clinical condition.

Conclusions: The findings made in the present study indicate that HLC, either as intact immunoglobulin or as HLCr, may provide useful information, particularly in identifying responders and confirm that the role of FLC is unreliable in monitoring patients with POEMS syndrome.

References

1. Dispenzieri A, Kyle RA, Lacy MQ, Rajkumar SV, Therneau TM, Larson DR, et al. POEMS syndrome: definitions and long-term outcome. Blood 2003;101:2496–506.10.1182/blood-2002-07-2299Search in Google Scholar PubMed

2. Dispenzieri A. POEMS syndrome: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol 2014;89:214–23.10.1002/ajh.23644Search in Google Scholar PubMed

3. Scarlato M, Previtali SC, Carpo M, Pareyson D, Briani C, Del Bo R, et al. Polyneuropathy in POEMS syndrome: role of angiogenic factors in the pathogenesis. Brain 2005;128:1911–20.10.1093/brain/awh519Search in Google Scholar PubMed

4. Soubrier M, Dubost JJ, Serre AF, Ristori JM, Sauvezie B, Cathebras P, et al. Growth factors in POEMS syndrome: evidence for a marked increase in circulating vascular endothelial growth factor. Arthritis Rheum 1997;40:786–7.10.1002/art.1780400430Search in Google Scholar PubMed

5. D’Souza A, Hayman SR, Buadi F, Mauermann M, Lacy MQ, Gertz MA, et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome. Blood 2011;118:4663–5.10.1182/blood-2011-06-362392Search in Google Scholar PubMed

6. Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673–80.10.1093/clinchem/47.4.673Search in Google Scholar

7. 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;23:215–24.10.1038/leu.2008.307Search in Google Scholar PubMed

8. Bradwell AR, Harding SJ, Fourrier NJ, Wallis GL, Drayson MT, Carr-Smith HD, et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin κ/λ ratios. Clin Chem 2009;55:1646–55.10.1373/clinchem.2009.123828Search in Google Scholar PubMed

9. Katzmann JA, Clark R, Kyle RA, Larson DR, Therneau TM, Melton LJ 3rd, et al. Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS. Leukemia 2013;27:208–12.10.1038/leu.2012.189Search in Google Scholar PubMed PubMed Central

10. Koulieris E, Panayiotidis P, Harding SJ, Kafasi N, Maltezas D, Bartzis V, et al. Ratio of involved/uninvolved immunoglobulin quantification by Hevylite™ assay: clinical and prognostic impact in multiple myeloma. Exp Hematol Oncol 2012;23:1–9.10.1186/2162-3619-1-9Search in Google Scholar PubMed PubMed Central

11. Katzmann JA, Willrich MA, Kohlhagen MC, Kyle RA, Murray DL, Snyder MR, et al. Monitoring IgA multiple myeloma: immunoglobulin heavy/light chain assays. Clin Chem 2015;61:360–7.10.1373/clinchem.2014.231985Search in Google Scholar PubMed

12. D’Souza A, Lacy M, Gertz M, Kumar S, Buadi F, Hayman S et al. Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience. Blood 2012;120:56–62.10.1182/blood-2012-04-423178Search in Google Scholar PubMed

13. Altinier S, Seguso M, Zaninotto M, Varagnolo M, Adami F, Angeli P, et al. Serum free light chain reference values: a critical approach. Clin Biochem 2013;46:691–3.10.1016/j.clinbiochem.2013.01.014Search in Google Scholar PubMed

14. Ludwig H, Milosavljevic D, Zojer N, Faint JM, Bradwell AR, Hübl W, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia 2013;27:213–9.10.1038/leu.2012.197Search in Google Scholar PubMed PubMed Central

15. Boyle EM, Fouquet G, Guidez S, Bonnet S, Demarquette H, Dulery R, et al. IgA kappa/IgA lambda heavy/light chain assessment in the management of patients with IgA myeloma. Cancer 2014;120:3952–7.10.1002/cncr.28946Search in Google Scholar PubMed

16. Stankowski-Drengler T, Gertz MA, Katzmann JA, Lacy MQ, Kumar S, Leung N, et al. Serum immunoglobulin free light chain measurements and heavy chain isotype usage provide insight into disease biology in patients with POEMS syndrome. Am J Hematol 2010;85:431–4.10.1002/ajh.21707Search in Google Scholar PubMed PubMed Central

17. Wang C, Su W, Zhang W, Di Q, Duan MH, Ji W, et al. Serum immunoglobulin free light chain and heavy/light chain measurements in POEMS syndrome. Ann Hematol 2014;93:1201–6.10.1007/s00277-014-2019-ySearch in Google Scholar PubMed

18. Wang C, Su W, Cai QQ, Cai H, Ji W, Di Q, et al. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome. Eur J Haematol 2015. doi:10.1111/ejh.12682.Search in Google Scholar PubMed

Received: 2015-9-18
Accepted: 2016-3-2
Published Online: 2016-4-12
Published in Print: 2016-6-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Protein electrophoresis and serum free light chains in the diagnosis and monitoring of plasma cell disorders: laboratory testing and current controversies
  4. Laboratory Testing as Recommended by the Guidelines and the International Myeloma Working Group
  5. Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias
  6. Free light chain testing for the diagnosis, monitoring and prognostication of AL amyloidosis
  7. Laboratory testing in monoclonal gammopathy of renal significance (MGRS)
  8. The impact of renal function on the clinical performance of FLC measurement in AL amyloidosis
  9. Serum and Urine Protein Electrophoresis and Immunofixation Testing
  10. Challenges of measuring monoclonal proteins in serum
  11. Screening immunofixation should replace protein electrophoresis as the initial investigation of monoclonal gammopathy: Point
  12. Should routine laboratories stop doing screening serum protein electrophoresis and replace it with screening immune-fixation electrophoresis? No quick fixes: Counterpoint
  13. Moving towards harmonized reporting of serum and urine protein electrophoresis
  14. Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis
  15. Use of isoelectric focusing to discriminate transient oligoclonal bands from monoclonal protein in treated myeloma
  16. New patterns of relapse in multiple myeloma: a case of “light chain escape” in which FLC predicted relapse earlier than urine and serum immunofixation
  17. Serum Free Light Chain Methods and Controversies
  18. Analytical issues of serum free light chain assays and the relative performance of polyclonal and monoclonal based reagents
  19. Measurement of free light chains with assays based on monoclonal antibodies
  20. Measurement of free light chains – pros and cons of current methods
  21. Is accuracy of serum free light chain measurement achievable?
  22. Performance goals for immunoglobulins and serum free light chain measurements in plasma cell dyscrasias can be based on biological variation
  23. A patient with AL amyloidosis with negative free light chain results
  24. Strengths and weaknesses of methods for identifying monoclonal free light chains of Ig: examples from two cases with renal disease
  25. Comparison of Freelite™ and N Latex serum free light chain assays in subjects with end stage kidney disease on haemodialysis
  26. New Laboratory Assays and Challenges
  27. Quantification of β-region IgA monoclonal proteins – should we include immunochemical Hevylite® measurements? Point
  28. Quantification of β region IgA paraproteins – should we include immunochemical “heavy/light chain” measurements? Counterpoint
  29. Free light chains and heavy/light chains in monitoring POEMS patients
  30. Monitoring free light chains in serum using mass spectrometry
  31. Monoclonal antibody therapeutics as potential interferences on protein electrophoresis and immunofixation
  32. Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference
  33. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)
  34. Letter to the Editor
  35. Discrepancy between FLC assays: only a problem of quantification?
Downloaded on 7.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2015-0910/pdf
Scroll to top button