Assessment of Systemic and Gastrointestinal Tissue Damage Biomarkers for GVHD Risk Stratification

• Published in: Blood advances Vol. 6; no. 12; pp. 3707 - 3715
• Main Authors: Etra, Aaron, Gergoudis, Stephanie, Morales, George, Spyrou, Nikolaos, Shah, Jay, Kowalyk, Steven, Ayuk, Francis, Baez, Janna, Chanswangphuwana, Chantiya, Chen, Yi-Bin, Choe, Hannah, DeFilipp, Zachariah, Gandhi, Isha, Hexner, Elizabeth, Hogan, William J., Holler, Ernst, Kapoor, Urvi, Kitko, Carrie L., Kraus, Sabrina, Lin, Jung-Yi, Al Malki, Monzr, Merli, Pietro, Pawarode, Attaphol, Pulsipher, Michael A., Qayed, Muna, Reshef, Ran, Rosler, Wolf, Schechter, Tal, Van Hyfte, Grace, Weber, Daniela, Wolfl, Matthias, Young, Rachel, Özbek, Umut, Ferrara, James L.M., Levine, John E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.06.2022
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2022007296

We used a rigorous PRoBE study design to compare the ability of biomarkers of systemic inflammation and biomarkers of GI tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft vs. host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n=730) from 19 centers, divided them into training (n=352) and validation cohorts (n=378), and measured TNFR1, TIM3, IL6, ST2, and REG3α via ELISA. Performances of the 4 strongest algorithms from the training cohort (TNFR1+TIM3, TNFR1+ST2, TNFR1+REG3α, ST2+REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1+TIM3) had a significantly smaller area under the curve (AUC, 0.57) than the AUCs of algorithms that contained at least 1 GI damage biomarker (TNFR1+ST2, 0.70; TNFR1+REG3α, 0.73; ST2+REG3α, 0.79; all p<0.001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints.