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Biomarker Panel for Chronic Graft-Versus-Host Disease
Jeffrey Yu1, Barry E Storer1, Kushi Kushekhar1
1Jeffrey Yu, Kushi Kushekhar, Mohammad Abu Zaid, and Sophie Paczesny, Indiana University School of Medicine, Indianapolis, IN; Barry E. Storer, Paul J. Martin, Mary E. Flowers, John A. Hansen, Stephanie J. Lee, Qing Zhang, Philip R. Gafken, and Yuko Ogata, Fred Hutchinson Cancer Research Center; Barry E. Storer, University of Washington School of Medicine, Seattle, WA; Mukta Arora, University of Minnesota, Minneapolis, MN; Corey Cutler, Dana-Farber Cancer Institute, Boston, MA; Madan Jagasia, Vanderbilt University, Nashville, TN; Joseph Pidala, H. Lee Moffitt Cancer Center, Tampa, FL; Betty K. Hamilton, Cleveland Clinic Foundation, Cleveland, OH; George L. Chen, Roswell Park Cancer Institute, Buffalo, NY; and Iskra Pusic, Washington University School of Medicine, St Louis, MO.
A new four-biomarker panel aids in identifying patients at risk for chronic graft-versus-host disease (cGVHD) after hematopoietic cell transplantation (HCT). This panel can stratify patients for cGVHD risk at diagnosis or 100 days post-HCT.
Area of Science:
- Hematology
- Immunology
- Proteomics
Background:
- Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic hematopoietic cell transplantation (HCT).
- Identifying reliable diagnostic and prognostic markers for cGVHD is crucial for improving patient outcomes and managing morbidity and mortality.
Purpose of the Study:
- To discover and validate a panel of biomarkers for the diagnosis and prognosis of cGVHD.
- To assess the utility of these biomarkers in stratifying patients based on cGVHD risk.
Main Methods:
- Quantitative proteomics was employed to compare plasma samples from HCT patients with and without cGVHD.
- Candidate biomarkers were selected based on differential expression, pathway involvement, and assay availability.
- A four-biomarker panel (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) was evaluated in independent verification cohorts.
Main Results:
- The four-biomarker panel demonstrated a strong correlation with cGVHD diagnosis, severity, and nonrelapse mortality (AUC = 0.89).
- The panel successfully distinguished patients with cGVHD in a second verification cohort (AUC = 0.75).
- Measured at day +100 post-HCT, the panel predicted cGVHD development within 3 months, with improved accuracy when combined with clinical risk factors (AUC = 0.67 and 0.79, respectively).
Conclusions:
- A validated four-biomarker panel shows promise for diagnosing and predicting cGVHD.
- This biomarker panel can aid in patient stratification for cGVHD risk at diagnosis or at day +100 after HCT.
- The findings support the potential clinical utility of this panel in managing HCT recipients.
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