Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification.
Aaron EtraStephanie GergoudisGeorge MoralesNikolaos SpyrouJay ShahSteven KowalykFrancis AyukJanna BaezChantiya ChanswangphuwanaYi-Bin ChenHannah ChoeZachariah DeFilippIsha GandhiElizabeth O HexnerWilliam J HoganErnst HollerUrvi KapoorCarrie L KitkoSabrina KrausJung-Yi LinMonzr Al MalkiPietro MerliAttaphol PawarodeMichael A PulsipherMuna QayedRan ReshefWolf RöslerTal SchechterGrace Van HyfteDaniela WeberMatthias WölflRachel YoungUmut ÖzbekJames L M FerraraJohn E LevinePublished in: Blood advances (2022)
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.
Keyphrases
- machine learning
- newly diagnosed
- deep learning
- oxidative stress
- allogeneic hematopoietic stem cell transplantation
- end stage renal disease
- chronic kidney disease
- randomized controlled trial
- high resolution
- type diabetes
- peritoneal dialysis
- cross sectional
- patient reported outcomes
- acute myeloid leukemia
- virtual reality
- mass spectrometry
- combination therapy
- smoking cessation
- living cells
- single molecule
- replacement therapy
- fluorescent probe