{"id":129479,"date":"2021-10-24T21:23:36","date_gmt":"2021-10-25T04:23:36","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2021\/10\/blood-mass-spectrometry-detects-residual-disease-better-than-standard-techniques-in-light-chain-amyloidosis"},"modified":"2021-10-24T21:23:36","modified_gmt":"2021-10-25T04:23:36","slug":"blood-mass-spectrometry-detects-residual-disease-better-than-standard-techniques-in-light-chain-amyloidosis","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2021\/10\/blood-mass-spectrometry-detects-residual-disease-better-than-standard-techniques-in-light-chain-amyloidosis","title":{"rendered":"Blood mass spectrometry detects residual disease better than standard techniques in light-chain amyloidosis"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/blood-mass-spectrometry-detects-residual-disease-better-than-standard-techniques-in-light-chain-amyloidosis.jpg\"><\/a><\/p>\n<p>The Mayo Foundation Institutional Review Board (IRB) approved the study. All patients gave written informed consent to have their medical records reviewed and samples analyzed according to IRB requirements and federal regulations. Patients were eligible for this retrospective study if they: were diagnosed with AL amyloidosis between January 2000 and May 2015; were classified as amyloidosis complete hematologic response by immunofixation electrophoresis (IFE), serum free light chain (FLC) by consensus criteria;<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 6\" title=\"Palladini, G. 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. 30 4541&ndash;4549 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR6\" id=\"ref-link-section-d90921305e660\">6<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 7\" title=\"Comenzo, R. L. et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain (AL) amyloidosis. Leukemia 26 2317&ndash;2325 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR7\" id=\"ref-link-section-d90921305e663\">7<\/a><\/sup> had a negative bone marrow by six-color flow cytometry; and had both a stored research sample prior to starting a line of therapy and a repeat sample while in complete hematologic response. The diagnosis of amyloidosis was made by Congo red with green birefringence under polarized light; the typing of the amyloid was with immunohistochemical stains or proteomics<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 8\" title=\"Vrana, J. A. et al. Classification of amyloidosis by laser microdissection and mass spectrometry based proteomic analysis in clinical biopsy specimens. Blood 114 4957&ndash;4959 (2009).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR8\" id=\"ref-link-section-d90921305e667\">8<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 9\" title=\"Brambilla, F. et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood 119 1844&ndash;1847 (2012).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR9\" id=\"ref-link-section-d90921305e670\">9<\/a><\/sup>. Supplementary Figure <a data-track=\"click\" data-track-label=\"link\" data-track-action=\"supplementary material anchor\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#MOESM1\">1<\/a> is a consort diagram illustrating patient selection. Median time from institution of therapy to complete response (CR) sample was 18 months (interquartile range 9.1, 20 months).<\/p>\n<p>The serum IFE (SIFE), urine IFE (UIFE), FLC, and bone marrow measurements were done as part of routine clinical practice as previously described<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Kohlhagen, M. C. et al. Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1345&ndash;1352 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR4\" id=\"ref-link-section-d90921305e680\">4<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Mills, J. R. et al. Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1334&ndash;1344 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR5\" id=\"ref-link-section-d90921305e683\">5<\/a><\/sup>. Urine samples were concentrated to a maximum of 200\u00d7 to achieve final concentrations of urine protein between 20 and 80 g\/L<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Kohlhagen, M. C. et al. Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1345&ndash;1352 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR4\" id=\"ref-link-section-d90921305e687\">4<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Mills, J. R. et al. Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1334&ndash;1344 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR5\" id=\"ref-link-section-d90921305e690\">5<\/a><\/sup>. The FLC assay (Freelite\u2122, The Binding Site Ltd.) was performed on a Siemens BNII nephelometer<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 10\" title=\"Katzmann, J. A. et al. 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. 48 1437&ndash;1444 (2002).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR10\" id=\"ref-link-section-d90921305e694\">10<\/a><\/sup>, and an abnormal FLC result was defined as an abnormal FLC \u03ba\/\u03bb ratio. Bone marrow clonality was determined by six-color flow cytometry<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 11\" title=\"Morice, W. G. et al. Novel multi-parameter flow cytometry sensitively detects phenotypically distinct plasma cell subsets in plasma cell proliferative disorders. Leukemia 21 2043&ndash;2046 (2007).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR11\" id=\"ref-link-section-d90921305e698\">11<\/a><\/sup>. This method has sensitivity of ~10<sup>\u22124<\/sup> to 10<sup>\u22125<\/sup>.<\/p>\n<p>For MASS-FIX, immunoglobulins were enriched from serum using camelid-derived nanobodies directed against the heavy-chain constant domains of IgG, IgA, and IgM or the light-chain constant domains of \u03ba and \u03bb (Thermo Fisher Scientific)<sup><a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 4\" title=\"Kohlhagen, M. C. et al. Screening method for M-proteins in serum using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1345&ndash;1352 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR4\" id=\"ref-link-section-d90921305e710\">4<\/a>,<a data-track=\"click\" data-track-action=\"reference anchor\" data-track-label=\"link\" data-test=\"citation-ref\" aria-label=\"Reference 5\" title=\"Mills, J. R. et al. Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin. Chem. 62 1334&ndash;1344 (2016).\" href=\"https:\/\/www.nature.com\/articles\/s41408-020-0291-8#ref-CR5\" id=\"ref-link-section-d90921305e713\">5<\/a><\/sup>. The +1 and +2 charge states of the light chains and heavy chains were measured by configuring the mass spectrometer to analyze ions between an <i>m<\/i>\/<i>z<\/i> of 9000\u201332,000 Da.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The Mayo Foundation Institutional Review Board (IRB) approved the study. All patients gave written informed consent to have their medical records reviewed and samples analyzed according to IRB requirements and federal regulations. Patients were eligible for this retrospective study if they: were diagnosed with AL amyloidosis between January 2000 and May 2015; were classified as [\u2026]<\/p>\n","protected":false},"author":513,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,19],"tags":[],"class_list":["post-129479","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-chemistry"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/129479","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/513"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=129479"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/129479\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=129479"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=129479"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=129479"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}