A Validated Risk Stratification That Incorporates MAGIC Biomarkers Predicts Long-Term Outcomes in Pediatric Patients with Acute GVHD

TY - JOUR

T1 - A Validated Risk Stratification That Incorporates MAGIC Biomarkers Predicts Long-Term Outcomes in Pediatric Patients with Acute GVHD

AU - Qayed, Muna

AU - Kapoor, Urvi

AU - Gillespie, Scott

AU - Westbrook, Adrianna

AU - Aguayo-Hiraldo, Paibel

AU - Ayuk, Francis A

AU - Aziz, Mina

AU - Baez, Janna

AU - Choe, Hannah

AU - DeFilipp, Zachariah

AU - Etra, Aaron

AU - Grupp, Stephan A

AU - Hexner, Elizabeth

AU - Holler, Ernst

AU - Hogan, William J

AU - Kowalyk, Steven

AU - Merli, Pietro

AU - Morales, George

AU - Nakamura, Ryotaro

AU - Pulsipher, Michael A

AU - Schechter, Tal

AU - Shah, Jay

AU - Spyrou, Nikolaos

AU - Srinagesh, Hrishikesh K

AU - Wölfl, Matthias

AU - Yanik, Gregory

AU - Young, Rachel

AU - Kitko, Carrie L

AU - Ferrara, James L M

AU - Levine, John E

N1 - Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2024/6

Y1 - 2024/6

N2 - Acute graft versus host disease (GVHD) is a common and serious complication of allogeneic hematopoietic cell transplantation (HCT) in children but overall clinical grade at onset only modestly predicts response to treatment and survival outcomes. Two tools to assess risk at initiation of treatment were recently developed. The Minnesota risk system stratifies children for risk of nonrelapse mortality (NRM) according to the pattern of GVHD target organ severity. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm of 2 serum biomarkers (ST2 and REG3α) predicts NRM in adult patients but has not been validated in a pediatric population. We aimed to develop and validate a system that stratifies children at the onset of GVHD for risk of 6-month NRM. We determined the MAGIC algorithm probabilities (MAPs) and Minnesota risk for a multicenter cohort of 315 pediatric patients who developed GVHD requiring treatment with systemic corticosteroids. MAPs created 3 risk groups with distinct outcomes at the start of treatment and were more accurate than Minnesota risk stratification for prediction of NRM (area under the receiver operating curve (AUC), .79 versus .62, P = .001). A novel model that combined Minnesota risk and biomarker scores created from a training cohort was more accurate than either biomarkers or clinical systems in a validation cohort (AUC .87) and stratified patients into 2 groups with highly different 6-month NRM (5% versus 38%, P < .001). In summary, we validated the MAP as a prognostic biomarker in pediatric patients with GVHD, and a novel risk stratification that combines Minnesota risk and biomarker risk performed best. Biomarker-based risk stratification can be used in clinical trials to develop more tailored approaches for children who require treatment for GVHD.

AB - Acute graft versus host disease (GVHD) is a common and serious complication of allogeneic hematopoietic cell transplantation (HCT) in children but overall clinical grade at onset only modestly predicts response to treatment and survival outcomes. Two tools to assess risk at initiation of treatment were recently developed. The Minnesota risk system stratifies children for risk of nonrelapse mortality (NRM) according to the pattern of GVHD target organ severity. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm of 2 serum biomarkers (ST2 and REG3α) predicts NRM in adult patients but has not been validated in a pediatric population. We aimed to develop and validate a system that stratifies children at the onset of GVHD for risk of 6-month NRM. We determined the MAGIC algorithm probabilities (MAPs) and Minnesota risk for a multicenter cohort of 315 pediatric patients who developed GVHD requiring treatment with systemic corticosteroids. MAPs created 3 risk groups with distinct outcomes at the start of treatment and were more accurate than Minnesota risk stratification for prediction of NRM (area under the receiver operating curve (AUC), .79 versus .62, P = .001). A novel model that combined Minnesota risk and biomarker scores created from a training cohort was more accurate than either biomarkers or clinical systems in a validation cohort (AUC .87) and stratified patients into 2 groups with highly different 6-month NRM (5% versus 38%, P < .001). In summary, we validated the MAP as a prognostic biomarker in pediatric patients with GVHD, and a novel risk stratification that combines Minnesota risk and biomarker risk performed best. Biomarker-based risk stratification can be used in clinical trials to develop more tailored approaches for children who require treatment for GVHD.

KW - Humans

KW - Graft vs Host Disease/blood

KW - Child

KW - Biomarkers/blood

KW - Female

KW - Male

KW - Hematopoietic Stem Cell Transplantation/adverse effects

KW - Child, Preschool

KW - Adolescent

KW - Pancreatitis-Associated Proteins/blood

KW - Acute Disease

KW - Risk Assessment

KW - Infant

KW - Interleukin-1 Receptor-Like 1 Protein/blood

KW - Algorithms

KW - Transplantation, Homologous/adverse effects

KW - Treatment Outcome

U2 - 10.1016/j.jtct.2024.03.022

DO - 10.1016/j.jtct.2024.03.022

M3 - SCORING: Journal article

C2 - 38548227

VL - 30

SP - 603.e1-603.e11

JO - TRANSPL CELL THER

JF - TRANSPL CELL THER

SN - 2666-6375

IS - 6

ER -