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@ARTICLE{Pabst:182099,
author = {C. Pabst and N. Schreck$^*$ and A. Benner$^*$ and U.
Hegenbart and S. Schönland and A. Radujkovic and M. Schmitt
and C. Müller-Tidow and L. Orsatti and P. Dreger and T.
Luft},
title = {{S}tatin-based endothelial prophylaxis and outcome after
allogeneic stem cell transplantation.},
journal = {European journal of clinical investigation},
volume = {53},
number = {2},
issn = {0014-2972},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DKFZ-2022-02417},
pages = {e13883},
year = {2023},
note = {2023 Feb;53(2):e13883},
abstract = {Allogeneic haematopoietic stem cell transplantation
(alloSCT) often remains the only curative therapy for
hematologic malignancies. Although the management of
transplant-associated adverse events considerably improved
over the last decades, nonrelapse mortality (NRM) remains a
challenge, and endothelial dysfunction was identified as a
major contributor to NRM.Statin-based endothelial
prophylaxis (SEP) has been implemented in the standard of
care in our transplant centre to reduce NRM caused by
endothelial injury. Here, we retrospectively analysed the
impact of SEP on clinical outcome in a cohort of 347 alloSCT
patients.SEP (n = 209) was associated with significantly
reduced NRM (hazard ratio 0.61, $95\%$ CI 0.38-0.96) and
better overall survival (OS) after acute graft-versus-host
disease (HR 0.59, $95\%$ CI 0.37-0.93). Subgroup analyses
showed that the NRM benefit was mainly found in patients
with an intermediate endothelial activation and stress index
(EASIX), while relapse risk was not affected. On day 100
post-alloSCT, patients receiving SEP had significantly
higher levels of the rate-limiting enzyme of tryptophan
metabolism, indoleamine 2,3-dioxygenase (IDO), higher
kynurenine to tryptophan ratios as a proxy of IDO activity
and tended to have lower levels of the endothelial injury
marker ST2 (p = .055). No significant differences in
interferon-gamma or IL18 levels were observed. These
biomarker signatures suggest that the beneficial effects of
SEP might be mediated by both endothelial protection and
immunomodulation.Together, these data suggest that SEP
improves NRM and OS post-alloSCT in particular in patients
with intermediate endothelial risk and provide first
mechanistic clues about its potential mode of action.},
keywords = {allogeneic stem cell transplantation (Other) / endothelial
damage (Other) / endothelial protection (Other) /
immunosuppression (Other) / statin (Other) / thrombotic
microangiopathy (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:36199203},
doi = {10.1111/eci.13883},
url = {https://inrepo02.dkfz.de/record/182099},
}