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@ARTICLE{Weber:275253,
author = {D. Weber and M. Weber and E. Meedt and S. Ghimire and D.
Wolff and M. Edinger and H. Poeck and A. Hiergeist and A.
Gessner and F. Ayuk and W. Roesler and M. Wölfl and S.
Kraus and R. Zeiser and H. Bertrand and P. Bader and E.
Ullrich$^*$ and M. Eder and S. Gleich and R. Young and W.
Herr and J. E. Levine and J. L. M. Ferrara and E. Holler},
title = {{R}eg3α concentrations at day of allogeneic stem cell
transplantation predict outcome and correlate with early
antibiotic use.},
journal = {Blood advances},
volume = {7},
number = {7},
issn = {2473-9529},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2023-00700},
pages = {1326 - 1335},
year = {2023},
abstract = {Intestinal microbiome diversity plays an important role in
the pathophysiology of acute gastrointestinal (GI)
graft-versus-host disease (GVHD) and influences the outcome
of patients after allogeneic stem cell transplantation
(ASCT). We analyzed clinical data and blood samples taken
preconditioning and on the day of ASCT from 587 patients
from 7 German centers of the Mount Sinai Acute GVHD
International Consortium, dividing them into single-center
test (n = 371) and multicenter validation (n = 216) cohorts.
Regenerating islet-derived 3α (Reg3α) serum concentration
of day 0 correlated with clinical data as well as urinary
3-indoxylsulfate (3-IS) and Clostridiales group XIVa,
indicators of intestinal microbiome diversity. High Reg3α
concentration at day 0 of ASCT was associated with higher
1-year transplant-related mortality (TRM) in both cohorts (P
< .001). Cox regression analysis revealed high Reg3α at day
0 as an independent prognostic factor for 1-year TRM.
Multivariable analysis showed an independent correlation of
high Reg3α concentrations at day 0 with early systemic
antibiotic (AB) treatment. Urinary 3-IS (P = .04) and
Clostridiales group XIVa (P = .004) were lower in patients
with high vs those with low day 0 Reg3α concentrations. In
contrast, Reg3α concentrations before conditioning therapy
correlated neither with TRM nor disease or treatment-related
parameters. Reg3α, a known biomarker of acute GI GVHD
correlates with intestinal dysbiosis, induced by early AB
treatment in the period of pretransplant conditioning. Serum
concentrations of Reg3α measured on the day of graft
infusion are predictive of the risk for TRM of ASCT
recipients.},
keywords = {Humans / Anti-Bacterial Agents / Biomarkers / Graft vs Host
Disease: diagnosis / Graft vs Host Disease: etiology /
Hematopoietic Stem Cell Transplantation: adverse effects /
Transplantation, Homologous / Anti-Bacterial Agents (NLM
Chemicals) / Biomarkers (NLM Chemicals) / REG3A protein,
human (NLM Chemicals)},
cin = {FM01},
ddc = {610},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36350750},
doi = {10.1182/bloodadvances.2022008480},
url = {https://inrepo02.dkfz.de/record/275253},
}