A Biomarker-Integrated Day 7 Response Reliably Predicts Outcomes in Minnesota Standard Risk Acute GVHD
Year: 2026
Type: preprint
Abstract: ABSTRACT Acute graft-versus-host disease (GVHD) response is conventionally assessed 28 days after treatment initiation, although treatment escalation often occurs earlier. In Minnesota standard risk acute GVHD, day 7 clinical response alone provides limited prognostic discrimination because many patients without early improvement subsequently respond without additional therapy. We hypothesized that incorporating serum GVHD biomarkers into a day 7 response assessment would improve early prognostic stratification. We studied 790 patients with Minnesota standard risk GVHD treated with systemic therapy. A MAGIC observational cohort was randomly divided into training (n=294) and validation (n=308) cohorts, and an independent interventional trial cohort (n=188) served as external validation. A classification and regression tree integrated day 7 clinical response with Ann Arbor biomarker scores to predict 6-month non-relapse mortality (NRM). The integrated model reclassified approximately 20% of patients, identifying clinical non-responders with low-risk biomarkers who had favorable outcomes and clinical responders with high-risk biomarkers who remained at increased risk. In the training cohort, the integrated model improved prediction of 6-month NRM compared with day 7 clinical response alone (AUC, 0.76 vs 0.63; P=.002) and performed comparably to conventional day 28 clinical response (AUC, 0.70). These findings were reproduced in both validation cohorts. Among day 7 clinical non-responders, biomarker status identified biologically favorable slow responders and also stratified outcomes among patients who received second-line therapy. A biomarker-integrated day 7 response assessment improves early prognostic stratification in Minnesota standard risk acute GVHD and may provide an earlier, more objective endpoint for clinical decision-making and future therapeutic trials.
Source: medRxiv
Authors: Ioannis Evangelos Louloudis, Amin Alousi, Tingyu Wang, Marcio Diniz, Daniela Weber, Francis Ayuk, Hannah Choe, Ingrid Vasova, Yi-Bin Chen, Muna Qayed, Ryotaro Nakamura, Hassan Alkhateeb, Aaron M Etra, Matthias Wölfl, Ran Reshef, Elizabeth Hexner, Carrie L Kitko, Paibel Aguayo-Hiraldo, Muhammad Ali, Peter Bader, Chantiya Chanswangphuwana, Matthias Eder, Sabrina Kraus, Margaret L MacMillan, John Magenau, Fotios V Michelis, Timothy Olson, Joseph Pidala, Pavan Reddy, Matthias Stelljes, Robert Zeiser, Yu Akahoshi, Janna Baez, Gilbert Eng, Sigrun Gleich, Nikolaos Katsivelos, George Morales, Tara Sebastian, Nikolaos Spyrou, Rachel Young, William J Hogan, James L M Ferrara, John E Levine
Institutions: Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, The University of Texas MD Anderson Cancer Center, University of Regensburg, University Medical Center Hamburg-Eppendorf, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsklinikum Erlangen, Massachusetts General Hospital, Emory University, City Of Hope National Medical Center, Mayo Clinic, Universitätsklinikum Würzburg, Columbia University Irving Medical Center, Abramson Cancer Center, University of Pennsylvania, Vanderbilt University Medical Center, University of Southern California, Children's Hospital Los Angeles, Hospital for Sick Children, Goethe University Frankfurt, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Medizinische Hochschule Hannover, University of Minnesota, University of Michigan, University of Toronto, Princess Margaret Cancer Centre, Children's Hospital of Philadelphia, Moffitt Cancer Center, Baylor College of Medicine, Dan L Duncan Comprehensive Cancer Center, University Hospital Münster, University of Freiburg, University Medical Center Freiburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7224240369