Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification. Academic Article uri icon

Overview

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.

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
  • Rösler, Wolf
  • Schechter, Tal
  • Van Hyfte, Grace
  • Weber, Daniela
  • Wölfl, Matthias
  • Young, Rachel
  • Özbek, Umut
  • Ferrara, James L M
  • Levine, John E

publication date

  • June 28, 2022

Research

keywords

  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation

Identity

PubMed Central ID

  • PMC9631548

Scopus Document Identifier

  • 85132076333

Digital Object Identifier (DOI)

  • 10.1182/bloodadvances.2022007296

PubMed ID

  • 35443021

Additional Document Info

volume

  • 6

issue

  • 12