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