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@ARTICLE{Vlker:285052,
author = {Völker, Lotta and Müller-Jensen, Leonie and Carl, Sophia
and Nay, Sandra and Möllenkamp, Thiemo Malte and
Schultze-Florey, Christian and Grote-Levi, Lea and
Jendretzky, Konstantin F and Konen, Franz Felix and
Könecke, Christian and Eder, Matthias and Panagiota,
Victoria and Heidel, Florian H and Bullinger, Lars and Damm,
Frederik and Frick, Mareike and Penack, Olaf and Ludwig,
Rebecca and Buß, Eric Anil and Boehmerle, Wolfgang and
Endres, Matthias and Gudi, Viktoria and Huehnchen, Petra and
Skripuletz, Thomas and Möhn, Nora},
title = {{T}he {B}erlin-{H}annover {ICANS} severity assessment-a
novel bedside test to evaluate {CAR} {T}-cell-associated
neurotoxicity.},
journal = {Frontiers in neurology},
volume = {17},
issn = {1664-2295},
address = {Lausanne},
publisher = {Frontiers Research Foundation},
reportid = {DZNE-2026-00176},
pages = {1726779},
year = {2026},
abstract = {Chimeric antigen receptor (CAR) T-cell therapy has
transformed the treatment of refractory hematological
malignancies but is frequently complicated by immune
effector cell-associated neurotoxicity syndrome (ICANS).
Early clinical recognition remains challenging, as the
commonly used Immune Effector Cell-Associated Encephalopathy
(ICE) score lacks sensitivity for subtle deficits.In this
prospective bicentric study, 100 patients treated with CAR
T-cells at Hannover Medical School and Charité -
Universitätsmedizin Berlin underwent systematic
neurological assessments using both ICE and the newly
developed Berlin-Hannover ICANS Severity Assessment (BHISA).
Examinations were performed at baseline prior to CAR T-cell
infusion, on day 6-7 (±1 day) post-infusion, and during
ICANS episodes. Data on the clinical course, other
toxicities, comorbidities, CAR T-cell products, and ICANS
treatment were collected.Thirty-seven patients $(37\%)$
developed ICANS, which was associated with preceding
cytokine release syndrome and specific CAR T-cell products.
While ICE scores clustered at maximum values both at
baseline and follow-up, BHISA showed a broader distribution
and higher sensitivity to subtle changes. Correlation
analyses confirmed agreement between ICE and BHISA, but
BHISA captured early cognitive decline more reliably.
Receiver operating characteristic analyses demonstrated
comparable diagnostic accuracy (BHISA: AUC = 0.783, ICE: AUC
= 0,777), with consistently higher sensitivity of BHISA at
matched specificity. (Specificity target = 0.7, BHISA
sensitivity = 0.743, ICE sensitivity = 0.571; Specificity
target = 0.8, BHISA sensitivity = 0.629, ICE sensitivity =
0.571).BHISA may provide a more sensitive and more
differentiated screening tool for ICANS than ICE by
incorporating additional cognitive and motor domains, while
remaining easy to use. This may enable earlier and more
nuanced detection of CAR T related neurotoxicity,
potentially improving patient monitoring across a
heterogeneous population.},
keywords = {BHISA (Other) / CAR T-cell therapy (Other) / ICANS (Other)
/ ICE (Other) / screening tools (Other)},
cin = {AG Endres},
ddc = {610},
cid = {I:(DE-2719)1811005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41648666},
pmc = {pmc:PMC12867840},
doi = {10.3389/fneur.2026.1726779},
url = {https://pub.dzne.de/record/285052},
}