Citations 1
Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification
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 , Holler, Ernst , Kapoor, Urvi , Kitko, Carrie L. , Lin, Jung-Yi, Pawarode, Attaphol , Rösler, Wolf, Schechter, Tal , Hyfte, Grace Van , Weber, Daniela , Wölfl, Matthias , Young, Rachel , Özbek, Umut , Ferrara, James L.M. , Hexner, Elizabeth , Lin, Jung-Yi , Merli, Pietro , Pulsipher, Michael A. , Qayed, Muna , Levine, John E , Spyrou, Nikolaos , Hexner, Elizabeth O. , Hogan, William J. , Kraus, Sabrina , Malki, Monzr M. Al , Reshef, Ran , Levine, John E.
Blood Advances | June 23, 2022 | Volume: 6 | Issue: 12 | Pages: 3707-3715
10.1182/bloodadvances.2022007296
Abstract We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (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-versus-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 (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and 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 ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the 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.