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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.
Insights
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.
Purpose:
To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT).
Patients And Methods:
Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day +100 after HCT was evaluated in plasma of a second verification cohort (n = 172).
Results:
Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day +100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively.
Conclusion:
We conclude that the biomarker panel measured at diagnosis or day +100 after HCT may allow patient stratification according to risk of cGVHD.
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