TY  - JOUR
AU  - Weber, Daniela
AU  - Weber, Markus
AU  - Meedt, Elisabeth
AU  - Ghimire, Sakhila
AU  - Wolff, Daniel
AU  - Edinger, Matthias
AU  - Poeck, Hendrik
AU  - Hiergeist, Andreas
AU  - Gessner, André
AU  - Ayuk, Francis
AU  - Roesler, Wolf
AU  - Wölfl, Matthias
AU  - Kraus, Sabrina
AU  - Zeiser, Robert
AU  - Bertrand, Hannah
AU  - Bader, Peter
AU  - Ullrich, Evelyn
AU  - Eder, Matthias
AU  - Gleich, Sigrun
AU  - Young, Rachel
AU  - Herr, Wolfgang
AU  - Levine, John E
AU  - Ferrara, James L M
AU  - Holler, Ernst
TI  - Reg3α concentrations at day of allogeneic stem cell transplantation predict outcome and correlate with early antibiotic use.
JO  - Blood advances
VL  - 7
IS  - 7
SN  - 2473-9529
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2023-00700
SP  - 1326 - 1335
PY  - 2023
AB  - 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.
KW  - Humans
KW  - Anti-Bacterial Agents
KW  - Biomarkers
KW  - Graft vs Host Disease: diagnosis
KW  - Graft vs Host Disease: etiology
KW  - Hematopoietic Stem Cell Transplantation: adverse effects
KW  - Transplantation, Homologous
KW  - Anti-Bacterial Agents (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - REG3A protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36350750
DO  - DOI:10.1182/bloodadvances.2022008480
UR  - https://inrepo02.dkfz.de/record/275253
ER  -