A Biomarker-Integrated Day 7 Response Reliably Predicts Outcomes in Minnesota Standard Risk Acute GVHD

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.

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Journal
medRxiv
Published
2026-10-29
DOI
https://doi.org/10.64898/2026.10.28.26366649
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
preprint

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preprint

A Biomarker-Integrated Day 7 Response Reliably Predicts Outcomes in Minnesota Standard Risk Acute GVHD

Matthias Stelljes, Francis Ayuk, Ingrid Vášová, John Martin Magenau et al.
2 links
medRxiv
Hematopoietic Stem Cell Transplantation
preprint

A Biomarker-Integrated Day 7 Response Reliably Predicts Outcomes in Minnesota Standard Risk Acute GVHD

Matthias Stelljes, Francis Ayuk, Ingrid Vášová, John Martin Magenau, Margaret L. MacMillan, 赤星佑, James L.M. Ferrara, Sigrun Gleich, Hannah Kyung Choe, Amin Majid Alousi, Chantiya Chanswangphuwana, Nikolaos Katsivelos, John E. Levine, Aaron M. Etra, Márcio A. Diniz, Paibel Ixia Aguayo-Hiraldo, Nikolaos Spyrou, Hassan B. Alkhateeb, Gilbert Eng, Carrie Lynn Kitko, Daniela Weber, Sabrina Kraus, Fotios V. Michelis, Matthias Wölfl, Pavan R. Reddy, George Morales, William J. Hogan, Tara Sebastian, Robert Zeiser, Ran Reshef, Elizabeth Olson Hexner, Ioannis Evangelos Louloudis, Peter Bader, Rachel A Young, Matthias Eder, Janna Baez, Yibin Chen, Ryotaro Nakamura, Timothy Olson, Joseph Pidala, Tingyu Wang, Muhammad Ali, Muna Qayed
preprint en

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.

medRxiv
Goethe University Frankfurt (DE), University of Southern California (US), City Of Hope National Medical Center (US), University of Minnesota (US), Mayo Clinic (US), Children's Hospital of Philadelphia (US), Children's Hospital of Los Angeles (US), The University of Texas MD Anderson Cancer Center (US), Emory University (US), Chulalongkorn University (TH), University of Freiburg (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), University of Toronto (CA), University of Michigan (US), Columbia University Irving Medical Center (US), The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US), University Medical Center Freiburg (DE), Hospital for Sick Children (CA), King Chulalongkorn Memorial Hospital (TH), Princess Margaret Cancer Centre (CA), Moffitt Cancer Center (US), Medizinische Hochschule Hannover (DE), Massachusetts General Hospital (US), Universitätsklinikum Erlangen (DE), University Hospital Münster (DE), University Medical Center Hamburg-Eppendorf (DE), Universitätsklinikum Würzburg (DE), University of Minnesota Medical Center (US), Children's Cancer Center (US), Abramson Cancer Center (US), Tisch Cancer Institute (US), The Ohio State University (US), University of Regensburg (DE), University of Pennsylvania (US), Vanderbilt University Medical Center (US), Icahn School of Medicine at Mount Sinai (US)
National Heart, Lung, and Blood Institute
Good health and well-being
Hematopoietic Stem Cell Transplantation
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