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

Muna Qayed; Urvi Kapoor; Scott Gillespie; Adrianna Westbrook; Paibel Aguayo-Hiraldo; Francis A Ayuk; Mina Aziz; Janna Baez; Hannah Choe; Zachariah DeFilipp; Aaron Etra; Stephan A Grupp; Elizabeth Hexner; Ernst Holler; William J Hogan; Steven Kowalyk; Pietro Merli; George Morales; Ryotaro Nakamura; Michael A Pulsipher; Tal Schechter; Jay Shah; Nikolaos Spyrou; Hrishikesh K Srinagesh; Matthias Wölfl; Gregory Yanik; Rachel Young; Carrie L Kitko; James L M Ferrara; John E Levine

doi:10.1016/j.jtct.2024.03.022

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

Transplant Cell Ther. 2024 Mar 27:S2666-6367(24)00294-X. doi: 10.1016/j.jtct.2024.03.022. Online ahead of print.

Authors

Muna Qayed¹, Urvi Kapoor², Scott Gillespie³, Adrianna Westbrook³, Paibel Aguayo-Hiraldo⁴, Francis A Ayuk⁵, Mina Aziz², Janna Baez², Hannah Choe⁶, Zachariah DeFilipp⁷, Aaron Etra², Stephan A Grupp⁸, Elizabeth Hexner⁹, Ernst Holler¹⁰, William J Hogan¹¹, Steven Kowalyk², Pietro Merli¹², George Morales², Ryotaro Nakamura¹³, Michael A Pulsipher¹⁴, Tal Schechter¹⁵, Jay Shah², Nikolaos Spyrou², Hrishikesh K Srinagesh², Matthias Wölfl¹⁶, Gregory Yanik¹⁷, Rachel Young², Carrie L Kitko¹⁸, James L M Ferrara², John E Levine²

Affiliations

¹ Emory University School of Medicine, Atlanta, Georgia; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia. Electronic address: mqayed@emory.edu.
² The Tisch Cancer Institute and Division of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
³ Pediatric Biostatistics Core, Department of Pediatrics, Emory University, Atlanta, Georgia.
⁴ Division of Hematology, Oncology, and BMT, Children's Hospital Los Angeles, Los Angeles, California.
⁵ Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Ohio State University Wexner Medical Center, Columbus, Ohio.
⁷ Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, Massachusetts.
⁸ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁹ Blood and Marrow Transplantation Program, Abramson Cancer Center and the Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
¹⁰ Department of Hematology and Oncology, Internal Medicine III, University of Regensburg, Regensburg, Germany.
¹¹ Division of Hematology, Mayo Clinic, Rochester, Minnesota.
¹² Ospedale Pediatrico Bambino Gesú, IRCCS, Rome, Italy.
¹³ Hematology/Hematopoietic Cell Transplant, City of Hope National Medical Center, Duarte, California.
¹⁴ Division of Hematology, Oncology, and BMT, Children's Hospital Los Angeles, Los Angeles, California; Division of Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute at the Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, Utah.
¹⁵ Division of Hematology/Oncology/BMT, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁶ Pediatric Blood and Marrow Transplantation Program, Children's Hospital, University of Würzburg, Würzburg, Germany.
¹⁷ Pediatric Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, Michigan.
¹⁸ Pediatric Blood and Marrow Transplant Program, Vanderbilt University Medical Center, Nashville, Tennessee.

PMID: 38548227
DOI: 10.1016/j.jtct.2024.03.022

Abstract

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.

Keywords: Acute GVHD; Biomarkers; Pediatric; Validation.