Eileen Boyle1, Salomon Manier1, Julie Lejeune2, Guillemette Fouquet1, Stephanie Guidez3, Sarah Bonnet1, Houria Debarri1, Helene Demarquette1, Remy Dulery1, Julie Gay1, Bernadette Hennache4, Brigitte Onraed4, Jean-Luc Faucompré4, Suzanna Schraen4, Thierry Facon1, Hervé Avet-Loiseau5, Sylvie Chevret2, Veronique Leblond6, Stephen Harding7, Xavier Leleu8.
Abstract
PURPOSE: Accurate quantification of monoclonal IgM immunoglobulins is essential for response assessment in patients with Waldenström's macroglobulinaemia (WM). The propensity of IgM to form multimers in serum makes sample evaluation by current laboratory methods particularly challenging. EXPERIMENTAL
DESIGN: We assessed the precision and linearity of IgMκ and IgMλ heavy/light chain (HLC, Hevylite) assays, and established reference intervals using 120 normal donor sera. We compared the quantitative performance of HLC assays with serum protein electrophoresis (SPE) and total IgM nephelometry for 78 diagnostic samples and follow-up samples from 25 patients with WM. Comparisons were made between the three methods for diagnostic sensitivity and response assessment.
RESULTS: IgMκ and IgMλ HLC assays showed low imprecision and good linearity. There was good agreement between summated HLC (IgMκ + IgMλ) and total IgM (measured nephelometrically; R2 = 0.90), but only moderate agreement between involved IgM HLC and SPE densitometry (R2 = 0.49). Analysis of 120 normal donor sera produced the following normal ranges: IgMκ: 0.29-1.82 g/L; IgMλ: 0.17-0.94 g/L; IgMκ/IgMλ ratio: 0.96-2.30. Using these ranges, IgM HLC ratios were abnormal in all WM presentation sera tested, including 15 with non-quantifiable SPE. Despite discordance in quantitation, responses assigned with HLC assays showed excellent agreement to those based on international guidelines using SPE or total IgM; although abnormal HLC ratios indicated residual disease in some patients with negative electrophoresis results.
CONCLUSIONS: Nephelometric assessment of IgMκ and IgMλ HLC pairs offers a quantitative alternative to traditional laboratory techniques for the measurement of monoclonal IgM and may aid in the management of WM. Clin Cancer Res; 22(20); 5152-8. ©2016 AACR. ©2016 American Association for Cancer Research.
PURPOSE: Accurate quantification of monoclonal IgM immunoglobulins is essential for response assessment in patients with Waldenström's macroglobulinaemia (WM). The propensity of IgM to form multimers in serum makes sample evaluation by current laboratory methods particularly challenging. EXPERIMENTAL
DESIGN: We assessed the precision and linearity of IgMκ and IgMλ heavy/light chain (HLC, Hevylite) assays, and established reference intervals using 120 normal donor sera. We compared the quantitative performance of HLC assays with serum protein electrophoresis (SPE) and total IgM nephelometry for 78 diagnostic samples and follow-up samples from 25 patients with WM. Comparisons were made between the three methods for diagnostic sensitivity and response assessment.
RESULTS: IgMκ and IgMλ HLC assays showed low imprecision and good linearity. There was good agreement between summated HLC (IgMκ + IgMλ) and total IgM (measured nephelometrically; R2 = 0.90), but only moderate agreement between involved IgM HLC and SPE densitometry (R2 = 0.49). Analysis of 120 normal donor sera produced the following normal ranges: IgMκ: 0.29-1.82 g/L; IgMλ: 0.17-0.94 g/L; IgMκ/IgMλ ratio: 0.96-2.30. Using these ranges, IgM HLC ratios were abnormal in all WM presentation sera tested, including 15 with non-quantifiable SPE. Despite discordance in quantitation, responses assigned with HLC assays showed excellent agreement to those based on international guidelines using SPE or total IgM; although abnormal HLC ratios indicated residual disease in some patients with negative electrophoresis results.
CONCLUSIONS: Nephelometric assessment of IgMκ and IgMλ HLC pairs offers a quantitative alternative to traditional laboratory techniques for the measurement of monoclonal IgM and may aid in the management of WM. Clin Cancer Res; 22(20); 5152-8. ©2016 AACR. ©2016 American Association for Cancer Research.
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Year: 2016
PMID： 27169996 DOI： 10.1158/1078-0432.CCR-15-2899
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531