eprintid: 10043921 rev_number: 29 eprint_status: archive userid: 608 dir: disk0/10/04/39/21 datestamp: 2018-02-22 17:16:09 lastmod: 2021-10-23 22:51:10 status_changed: 2018-02-22 17:16:09 type: article metadata_visibility: show creators_name: Sachchithanantham, S creators_name: Berlanga, O creators_name: Alvi, A creators_name: Mahmood, SA creators_name: Lachmann, HJ creators_name: Gillmore, JD creators_name: Hawkins, PN creators_name: Harding, S creators_name: Wechalekar, AD title: Immunoparesis defined by heavy plus light chain suppression is a novel marker of long-term outcomes in cardiac AL amyloidosis ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: hevylite; immunoparesis; amyloid; cardiac; freelite note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (≥2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26·2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0·05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0·33) and severe HLC immunoparesis trended towards poorer survival (20·2 vs. 42·8 months; P = 0·09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8·8 vs. 29·9 months, P = 0·007). In conclusion, severe HLC immunoparesis is an independent marker of long-term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study. date: 2017-11 date_type: published publisher: WILEY official_url: http://dx.doi.org/10.1111/bjh.14908 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Article verified: verified_manual elements_id: 1446949 doi: 10.1111/bjh.14908 lyricists_name: Gillmore, Julian lyricists_name: Hawkins, Philip lyricists_name: Lachmann, Helen lyricists_name: Mahmood, Ayesha lyricists_name: Sachchithanantham, Sajitha lyricists_name: Wechalekar, Ashutosh lyricists_id: JGILL78 lyricists_id: PNHAW77 lyricists_id: HJLAC80 lyricists_id: AMAHM84 lyricists_id: SSACH22 lyricists_id: AWECH53 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: British Journal of Haematology volume: 179 number: 4 pagerange: 575-585 pages: 11 issn: 1365-2141 citation: Sachchithanantham, S; Berlanga, O; Alvi, A; Mahmood, SA; Lachmann, HJ; Gillmore, JD; Hawkins, PN; ... Wechalekar, AD; + view all <#> Sachchithanantham, S; Berlanga, O; Alvi, A; Mahmood, SA; Lachmann, HJ; Gillmore, JD; Hawkins, PN; Harding, S; Wechalekar, AD; - view fewer <#> (2017) Immunoparesis defined by heavy plus light chain suppression is a novel marker of long-term outcomes in cardiac AL amyloidosis. British Journal of Haematology , 179 (4) pp. 575-585. 10.1111/bjh.14908 <https://doi.org/10.1111/bjh.14908>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10043921/1/Sachchithanantham_Immunoparesis.pdf