Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD

Etra A, Jurdi NE, Katsivelos N, Kwon D, Gergoudis S, Morales G, Spyrou N, Kowalyk S, Aguayo-Hiraldo P, Akahoshi Y, Ayuk F, Baez J, Betts BC, Chanswangphuwana C, Chen YB, Choe H, DeFilipp Z, Gleich S, Hexner E, Hogan WJ, Holler E, Kitko CL, Kraus S, Malki MA, MacMillan M, Pawarode A, Quagliarella F, Qayed M, Reshef R, Schechter T, Vasova I, Weisdorf D, Wölfl M, Young R, Nakamura R, Ferrara JL, Levine JE, Holtan S (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 8

Pages Range: 3284-3292

Journal Issue: 12

DOI: 10.1182/bloodadvances.2023011049

Abstract

Graft-versus-host disease (GVHD) is a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation. Algorithms containing either the gastrointestinal (GI) GVHD biomarker amphiregulin (AREG) or a combination of 2 GI GVHD biomarkers (suppressor of tumorigenicity-2 [ST2] + regenerating family member 3 alpha [REG3α]) when measured at GVHD diagnosis are validated predictors of NRM risk but have never been assessed in the same patients using identical statistical methods. We measured the serum concentrations of ST2, REG3α, and AREG by enzyme-linked immunosorbent assay at the time of GVHD diagnosis in 715 patients divided by the date of transplantation into training (2004-2015) and validation (2015-2017) cohorts. The training cohort (n = 341) was used to develop algorithms for predicting the probability of 12-month NRM that contained all possible combinations of 1 to 3 biomarkers and a threshold corresponding to the concordance probability was used to stratify patients for the risk of NRM. Algorithms were compared with each other based on several metrics, including the area under the receiver operating characteristics curve, proportion of patients correctly classified, sensitivity, and specificity using only the validation cohort (n = 374). All algorithms were strong discriminators of 12-month NRM, whether or not patients were systemically treated (n = 321). An algorithm containing only ST2 + REG3α had the highest area under the receiver operating characteristics curve (0.757), correctly classified the most patients (75%), and

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) Children's Hospital Los Angeles United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) University of Minnesota (UMN) United States (USA) (US) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH) Massachusetts General Hospital United States (USA) (US) Ohio State University United States (USA) (US) Universität Regensburg Germany (DE) Penn Medicine United States (USA) (US) Mayo Clinic United States (USA) (US) Vanderbilt University United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) City of Hope Medical Center United States (USA) (US) University of Michigan United States (USA) (US) Ospedale Pediatrico Bambino Gesu Italy (IT) Emory University United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) The Hospital for Sick Children (SickKids) Canada (CA) Julius-Maximilians-Universität Würzburg Germany (DE)

How to cite

APA:

Etra, A., Jurdi, N.E., Katsivelos, N., Kwon, D., Gergoudis, S., Morales, G.,... Holtan, S. (2024). Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD. Blood Advances, 8(12), 3284-3292. https://doi.org/10.1182/bloodadvances.2023011049

MLA:

Etra, Aaron, et al. "Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD." Blood Advances 8.12 (2024): 3284-3292.

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