Etra, Aaron and El Jurdi, Najla and Katsivelos, Nikolaos and Kwon, Deukwoo and Gergoudis, Stephanie and Morales, George and Spyrou, Nikolaos and Kowalyk, Steven and Aguayo-Hiraldo, Paibel and Akahoshi, Yu and Ayuk, Francis and Baez, Janna and Betts, Brian C. and Chanswangphuwana, Chantiya and Chen, Yi-Bin and Choe, Hannah and Defilipp, Zachariah and Gleich, Sigrun and Hexner, Elizabeth and Hogan, William J. and Holler, Ernst and Kitko, Carrie L. and Kraus, Sabrina and Al Malki, Monzr and Macmillan, Margaret and Pawarode, Attaphol and Quagliarella, Francesco and Qayed, Muna and Reshef, Ran and Schechter, Tal and Vasova, Ingrid and Weisdorf, Daniel and Woelfl, Matthias and Young, Rachel and Nakamura, Ryotaro and Ferrara, James L. M. and Levine, John E. and Holtan, Shernan (2024) Amphiregulin, ST2, and REG3 α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD. BLOOD ADVANCES, 8 (12). pp. 3284-3292. ISSN 2473-9529, 2473-9537
Full text not available from this repository. (Request a copy)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 [REG3 alpha]) 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, REG3 alpha, 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 classi fied, sensitivity, and speci ficity 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 + REG3 alpha had the highest area under the receiver operating characteristics curve (0.757), correctly classi fied the most patients (75%), and more accurately risk -strati fied those who developed Minnesota standard -risk GVHD and for patients who received posttransplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk -strati fied patients with Minnesota high -risk GVHD. Combining ST2, REG3 alpha, and AREG into a single algorithm did not improve performance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; FALSE DISCOVERY RATE; INITIAL THERAPY; PREVENTION; ACCURACY; CLASSIFICATION; PROMOTES; SURVIVAL; PHASE-2; CURVES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Aug 2025 07:35 |
| Last Modified: | 20 Aug 2025 07:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65604 |
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