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Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification

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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; 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.

In: BLOOD ADV, Vol. 6, No. 12, 28.06.2022, p. 3707-3715.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Etra, A, Gergoudis, S, Morales, G, Spyrou, N, Shah, J, Kowalyk, S, Ayuk, F, Baez, J, Chanswangphuwana, C, Chen, Y-B, Choe, H, DeFilipp, Z, Gandhi, I, Hexner, E, Hogan, WJ, Holler, E, Kapoor, U, Kitko, CL, Kraus, S, Lin, J-Y, Al Malki, M, Merli, P, Pawarode, A, Pulsipher, MA, Qayed, M, Reshef, R, Rösler, W, Schechter, T, Van Hyfte, G, Weber, D, Wölfl, M, Young, R, Özbek, U, Ferrara, JLM & Levine, JE 2022, 'Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification', BLOOD ADV, vol. 6, no. 12, pp. 3707-3715. https://doi.org/10.1182/bloodadvances.2022007296

APA

Etra, A., Gergoudis, S., Morales, G., Spyrou, N., Shah, J., Kowalyk, S., Ayuk, F., Baez, J., Chanswangphuwana, C., Chen, Y-B., Choe, H., DeFilipp, Z., Gandhi, I., Hexner, E., Hogan, W. J., Holler, E., Kapoor, U., Kitko, C. L., Kraus, S., ... Levine, J. E. (2022). Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification. BLOOD ADV, 6(12), 3707-3715. https://doi.org/10.1182/bloodadvances.2022007296

Vancouver

Etra A, Gergoudis S, Morales G, Spyrou N, Shah J, Kowalyk S et al. Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification. BLOOD ADV. 2022 Jun 28;6(12):3707-3715. https://doi.org/10.1182/bloodadvances.2022007296

Bibtex

@article{0a38684d638c40d1aaa3841137f3f55f,
title = "Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification",
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.",
keywords = "Biomarkers, Graft vs Host Disease/diagnosis, Hematopoietic Stem Cell Transplantation/adverse effects, Hepatitis A Virus Cellular Receptor 2, Humans, Inflammation, Interleukin-1 Receptor-Like 1 Protein, Prospective Studies, Receptors, Tumor Necrosis Factor, Type I, Retrospective Studies, Risk Assessment",
author = "Aaron Etra and Stephanie Gergoudis and George Morales and Nikolaos Spyrou and Jay Shah and Steven Kowalyk and Francis Ayuk and Janna Baez and Chantiya Chanswangphuwana and Yi-Bin Chen and Hannah Choe and Zachariah DeFilipp and Isha Gandhi and Elizabeth Hexner and Hogan, {William J} and Ernst Holler and Urvi Kapoor and Kitko, {Carrie L} and Sabrina Kraus and Jung-Yi Lin and {Al Malki}, Monzr and Pietro Merli and Attaphol Pawarode and Pulsipher, {Michael A} and Muna Qayed and Ran Reshef and Wolf R{\"o}sler and Tal Schechter and {Van Hyfte}, Grace and Daniela Weber and Matthias W{\"o}lfl and Rachel Young and Umut {\"O}zbek and Ferrara, {James L M} and Levine, {John E}",
note = "{\textcopyright} 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.",
year = "2022",
month = jun,
day = "28",
doi = "10.1182/bloodadvances.2022007296",
language = "English",
volume = "6",
pages = "3707--3715",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "12",

}

RIS

TY - JOUR

T1 - Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification

AU - Etra, Aaron

AU - Gergoudis, Stephanie

AU - Morales, George

AU - Spyrou, Nikolaos

AU - Shah, Jay

AU - Kowalyk, Steven

AU - Ayuk, Francis

AU - Baez, Janna

AU - Chanswangphuwana, Chantiya

AU - Chen, Yi-Bin

AU - Choe, Hannah

AU - DeFilipp, Zachariah

AU - Gandhi, Isha

AU - Hexner, Elizabeth

AU - Hogan, William J

AU - Holler, Ernst

AU - Kapoor, Urvi

AU - Kitko, Carrie L

AU - Kraus, Sabrina

AU - Lin, Jung-Yi

AU - Al Malki, Monzr

AU - Merli, Pietro

AU - Pawarode, Attaphol

AU - Pulsipher, Michael A

AU - Qayed, Muna

AU - Reshef, Ran

AU - Rösler, Wolf

AU - Schechter, Tal

AU - Van Hyfte, Grace

AU - Weber, Daniela

AU - Wölfl, Matthias

AU - Young, Rachel

AU - Özbek, Umut

AU - Ferrara, James L M

AU - Levine, John E

N1 - © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

PY - 2022/6/28

Y1 - 2022/6/28

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Graft vs Host Disease/diagnosis

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Hepatitis A Virus Cellular Receptor 2

KW - Humans

KW - Inflammation

KW - Interleukin-1 Receptor-Like 1 Protein

KW - Prospective Studies

KW - Receptors, Tumor Necrosis Factor, Type I

KW - Retrospective Studies

KW - Risk Assessment

U2 - 10.1182/bloodadvances.2022007296

DO - 10.1182/bloodadvances.2022007296

M3 - SCORING: Journal article

C2 - 35443021

VL - 6

SP - 3707

EP - 3715

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 12

ER -