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@ARTICLE{Korell:179663,
author = {F. Korell and O. Penack and M. Mattie and N. Schreck$^*$
and A. Benner$^*$ and J. Krzykalla$^*$ and Z. Wang and M.
Schmitt and L. Bullinger and C. Müller-Tidow and P. Dreger
and T. Luft},
title = {{EASIX} and {S}evere {E}ndothelial {C}omplications {A}fter
{CD}19-{D}irected {CAR}-{T} {C}ell {T}herapy-{A} {C}ohort
{S}tudy.},
journal = {Frontiers in immunology},
volume = {13},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2022-00835},
pages = {877477},
year = {2022},
abstract = {Endothelial dysfunction is associated with two main
complications of chimeric antigen receptor T (CAR-T) cell
therapy, cytokine release syndrome (CRS) and immune effector
cell-associated neurotoxicity syndrome (ICANS). This study
evaluates the Endothelial Activation and Stress Index
(EASIX) as a prognostic marker for high-grade CRS and ICANS
in patients treated with CD19-directed CAR-T cells.In this
retrospective study, a training cohort of 93 patients from
the ZUMA-1 trial and a validation cohort of 121 patients
from two independent centers (University Hospital
Heidelberg, Charité University Medicine Berlin) were
investigated. The primary objective was to assess the
predictive capacity of EASIX measured immediately before the
start of lymphodepletion (EASIX-pre) for the occurrence of
grade ≥3 CRS and/or ICANS. To explore a possible
endothelial link, serum levels of endothelial stress markers
(angiopoietin-2, suppressor of tumorigenicity-2, soluble
thrombomodulin, and interleukin-8) were determined before
lymphodepletion and on day 7 after CART infusion in the
validation cohort (n = 47).The prognostic effect of
EASIX-pre on grade ≥3 CRS and/or ICANS was significant in
the training cohort [OR 2-fold increase 1.72 (1.26-2.46)]
and validated in the independent cohort. An EASIX-pre cutoff
>4.67 derived from the training cohort associated with a
4.3-fold increased odds ratio of severe CRS/ICANS in the
independent cohort. Serum endothelial distress markers
measured on day+7 correlated with EASIX-pre and associated
with severe complications.EASIX-pre is a powerful predictor
of severe CRS/ICANS after CD19-directed CART therapy and
might be used as a basis for risk-adapted prevention
strategies.},
keywords = {CAR-T cell (Other) / CRS (Other) / EASIX (Other) / ICANS
(Other) / prognostic biomarker (Other)},
cin = {C060},
ddc = {610},
cid = {I:(DE-He78)C060-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35464403},
pmc = {pmc:PMC9033201},
doi = {10.3389/fimmu.2022.877477},
url = {https://inrepo02.dkfz.de/record/179663},
}