Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD
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Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD. / Etra, Aaron; El Jurdi, Najla; Katsivelos, Nikolaos; Kwon, Deukwoo; Gergoudis, Stephanie; Morales, George; Spyrou, Nikolaos; Kowalyk, Steven; Aguayo-Hiraldo, Paibel; Akahoshi, Yu; Ayuk, Francis; Baez, Janna; Betts, Brian C; Chanswangphuwana, Chantiya; Chen, Yi-Bin; Choe, Hannah; DeFilipp, Zachariah; Gleich, Sigrun; Hexner, Elizabeth; Hogan, William J; Holler, Ernst; Kitko, Carrie L; Kraus, Sabrina; Al Malki, Monzr; MacMillan, Margaret; Pawarode, Attaphol; Quagliarella, Francesco; Qayed, Muna; Reshef, Ran; Schechter, Tal; Vasova, Ingrid; Weisdorf, Daniel; Wölfl, Matthias; Young, Rachel; Nakamura, Ryotaro; Ferrara, James L M; Levine, John E; Holtan, Shernan.
In: BLOOD ADV, Vol. 8, No. 12, 25.06.2024, p. 3284-3292.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD
AU - Etra, Aaron
AU - El Jurdi, Najla
AU - Katsivelos, Nikolaos
AU - Kwon, Deukwoo
AU - Gergoudis, Stephanie
AU - Morales, George
AU - Spyrou, Nikolaos
AU - Kowalyk, Steven
AU - Aguayo-Hiraldo, Paibel
AU - Akahoshi, Yu
AU - Ayuk, Francis
AU - Baez, Janna
AU - Betts, Brian C
AU - Chanswangphuwana, Chantiya
AU - Chen, Yi-Bin
AU - Choe, Hannah
AU - DeFilipp, Zachariah
AU - Gleich, Sigrun
AU - Hexner, Elizabeth
AU - Hogan, William J
AU - Holler, Ernst
AU - Kitko, Carrie L
AU - Kraus, Sabrina
AU - Al Malki, Monzr
AU - MacMillan, Margaret
AU - Pawarode, Attaphol
AU - Quagliarella, Francesco
AU - Qayed, Muna
AU - Reshef, Ran
AU - Schechter, Tal
AU - Vasova, Ingrid
AU - Weisdorf, Daniel
AU - Wölfl, Matthias
AU - Young, Rachel
AU - Nakamura, Ryotaro
AU - Ferrara, James L M
AU - Levine, John E
AU - Holtan, Shernan
N1 - © 2024 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 - 2024/6/25
Y1 - 2024/6/25
N2 - 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 more accurately risk-stratified those who developed Minnesota standard-risk GVHD and for patients who received posttransplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk-stratified patients with Minnesota high-risk GVHD. Combining ST2, REG3α, and AREG into a single algorithm did not improve performance.
AB - 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 more accurately risk-stratified those who developed Minnesota standard-risk GVHD and for patients who received posttransplant cyclophosphamide-based prophylaxis. An algorithm containing only AREG more accurately risk-stratified patients with Minnesota high-risk GVHD. Combining ST2, REG3α, and AREG into a single algorithm did not improve performance.
KW - Humans
KW - Graft vs Host Disease/blood
KW - Interleukin-1 Receptor-Like 1 Protein/blood
KW - Biomarkers/blood
KW - Pancreatitis-Associated Proteins/blood
KW - Algorithms
KW - Male
KW - Female
KW - Middle Aged
KW - Adult
KW - Amphiregulin/blood
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Aged
KW - Prognosis
KW - Antigens, Neoplasm/blood
KW - Acute Disease
KW - Adolescent
KW - Young Adult
U2 - 10.1182/bloodadvances.2023011049
DO - 10.1182/bloodadvances.2023011049
M3 - SCORING: Journal article
C2 - 38640195
VL - 8
SP - 3284
EP - 3292
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 12
ER -