Reg3α levels at day of allogeneic stem cell transplantation predict outcome and correlate with early antibiotic use.

The intestinal microbiome diversity plays an important role in the pathophysiology of acute gastrointestinal (GI) Graft-versus-Host Disease (aGvHD) and influences the outcome of patients after allogeneic stem cell transplantation (SCT). We analyzed clinical data and blood samples taken pre-conditioning and on the day of allogeneic SCT from 587 patients from seven German centers of the Mount Sinai Acute GvHD International Consortium (MAGIC), dividing them into a single-center test cohort (n=371) and a multicenter validation cohort (n=216). Reg3α serum concentration of day 0 correlated with clinical data as well as urinary 3-Indoxylsulfate and Clostridiales group XIVa, indicators of intestinal microbiome diversity. High Reg3α concentration at day 0 of allogeneic SCT was associated with higher 1-year transplant-related mortality (TRM) in both cohorts (p<0.001). Cox regression analysis revealed high Reg3α at day 0 as an independent prognostic factor for 1-year TRM (HR=2.9, 95%CI=1.8-4.8, p<0.001). Multivariable analysis showed an independent correlation of high Reg3α concentrations at day 0 and early systemic antibiotic treatment (OR=3.1, 95% CI = 2.0-4.8, p<0.001). Urinary 3-Indoxylsulfate (p=0.04) and Clostridiales group XIVa (p=0.004) were lower in patients with high Reg3α day 0 concentrations than in low Reg3α patients. In contrast, Reg3α concentrations prior to conditioning therapy correlated with neither TRM nor disease or treatment-related parameters. Reg3α, a known biomarker of acute GI GvHD correlates with intestinal dysbiosis induced by early antibiotic 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 allogenic SCT recipients.