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@ARTICLE{Rejeski:283136,
author = {K. Rejeski and A. Perez and G. Iacoboni and V.
Blumenberg$^*$ and V. L. Bücklein$^*$ and S. Völkl and O.
Penack and O. Albanyan and S. Stock$^*$ and F. Müller and
P. Karschnia and A. Petrera and K. Reid and R. Faramand and
M. L. Davila and K. Modi and E. A. Dean and C. Bachmeier and
M. von Bergwelt-Baildon$^*$ and F. L. Locke and W. Bethge
and L. Bullinger$^*$ and A. Mackensen and P. Barba and M. D.
Jain and M. Subklewe$^*$},
title = {{S}evere hematotoxicity after {CD}19 {CAR}-{T} therapy is
associated with suppressive immune dysregulation and limited
{CAR}-{T} expansion.},
journal = {Science advances},
volume = {9},
number = {38},
issn = {2375-2548},
address = {Washington, DC [u.a.]},
publisher = {Assoc.},
reportid = {DKFZ-2023-01923},
pages = {eadg3919},
year = {2023},
abstract = {Prolonged cytopenias after chimeric antigen receptor (CAR)
T cell therapy are a significant clinical problem and the
underlying pathophysiology remains poorly understood. Here,
we investigated how (CAR) T cell expansion dynamics and
serum proteomics affect neutrophil recovery phenotypes after
CD19-directed CAR T cell therapy. Survival favored patients
with 'intermittent' neutrophil recovery (e.g., recurrent
neutrophil dips) compared to either 'quick' or 'aplastic'
recovery. While intermittent patients displayed increased
CAR T cell expansion, aplastic patients exhibited an
unfavorable relationship between expansion and tumor burden.
Proteomics of patient serum collected at baseline and in the
first month after CAR-T therapy revealed higher markers of
endothelial dysfunction, inflammatory cytokines, macrophage
activation, and T cell suppression in the aplastic phenotype
group. Prolonged neutrophil aplasia thus occurs in patients
with systemic immune dysregulation at baseline with
subsequently impaired CAR-T expansion and myeloid-related
inflammatory changes. The association between neutrophil
recovery and survival outcomes highlights critical
interactions between host hematopoiesis and the immune state
stimulated by CAR-T infusion.},
keywords = {Humans / Immunotherapy, Adoptive: adverse effects /
Receptors, Chimeric Antigen / Adaptor Proteins, Signal
Transducing / Antigens, CD19 / Cell Cycle / Receptors,
Chimeric Antigen (NLM Chemicals) / Adaptor Proteins, Signal
Transducing (NLM Chemicals) / Antigens, CD19 (NLM
Chemicals)},
cin = {MU01 / BE01},
ddc = {500},
cid = {I:(DE-He78)MU01-20160331 / I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37738350},
pmc = {pmc:PMC10516499},
doi = {10.1126/sciadv.adg3919},
url = {https://inrepo02.dkfz.de/record/283136},
}