Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment

• Published in: Blood Vol. 126; no. 1; pp. 113 - 120
• Main Authors: McDonald, George B., Tabellini, Laura, Storer, Barry E., Lawler, Richard L., Martin, Paul J., Hansen, John A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.07.2015; American Society of Hematology
• Subjects: Acute Disease; Adult; Aged; Biomarkers - blood; Female; Gastrointestinal Diseases - blood; Gastrointestinal Diseases - diagnosis; Gastrointestinal Diseases - etiology; Gastrointestinal Diseases - mortality; Graft vs Host Disease - blood; Graft vs Host Disease - diagnosis; Graft vs Host Disease - mortality; Graft vs Host Disease - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - mortality; Humans; Male; Middle Aged; Predictive Value of Tests; Recurrence; Retrospective Studies; Time Factors; Transplantation; Transplantation, Homologous; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-03-636753

We identified plasma biomarkers that presaged outcomes in patients with gastrointestinal graft-versus-host disease (GVHD) by measuring 23 biomarkers in samples collected before initiation of treatment. Six analytes with the greatest accuracy in predicting grade 3-4 GVHD in the first cohort (74 patients) were then tested in a second cohort (76 patients). The same 6 analytes were also tested in samples collected at day 14 ± 3 from 167 patients free of GVHD at the time. Logistic regression and calculation of an area under a receiver-operating characteristic (ROC) curve for each analyte were used to determine associations with outcome. Best models in the GVHD onset and landmark analyses were determined by forward selection. In samples from the second cohort, collected a median of 4 days before start of treatment, levels of TIM3, IL6, and sTNFR1 had utility in predicting development of peak grade 3-4 GVHD (area under ROC curve, 0.88). Plasma ST2 and sTNFR1 predicted nonrelapse mortality within 1 year after transplantation (area under ROC curve, 0.90). In the landmark analysis, plasma TIM3 predicted subsequent grade 3-4 GVHD (area under ROC curve, 0.76). We conclude that plasma levels of TIM3, sTNFR1, ST2, and IL6 are informative in predicting more severe GVHD and nonrelapse mortality. •Before GVHD treatment, informative plasma biomarkers included TIM3, IL6, sTNFR1 (for grade 3-4 GVHD), and ST2 and sTNFR1 (for NRM at 1 year).•In a day 14 landmark analysis, plasma TIM3 was predictive of grade 3-4 GVHD.