51. A Four Protein Plasma Fingerprint of Acute Graft Versus Host Disease (GVHD) Predicts Long Term Survival
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Joel Whitfield, Carrie L. Kitko, Angela C. Weyand, Thomas Braun, Dawn Jones, Sung Choi, John E. Levine, Shawn G. Clouthier, Dan Bickley, Krijanovski Oleg, Sophie Paczesny, and James L.M. Ferrara
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medicine.medical_specialty ,Training set ,biology ,Septic shock ,business.industry ,medicine.medical_treatment ,Immunology ,C-reactive protein ,Epley maneuver ,Cell Biology ,Hematology ,medicine.disease ,Logistic regression ,Biochemistry ,Gastroenterology ,Surgery ,Idiopathic pneumonia syndrome ,Internal medicine ,Acute graft versus host disease ,Long term survival ,medicine ,biology.protein ,business - Abstract
There are no independent laboratory diagnostic tests for acute GVHD. We first identified 7 potential plasma biomarkers (IL-2R-α, CRP, IL-8, TIMP-1, TNFR1, HGF, CA-19.9) of acute GVHD using a combination of proteomic approaches and antibody microarrays. We next conducted a retrospective analysis using plasma samples from 424 patients at the University of Michigan under IRB approval. We obtained samples at the first clinical signs of acute GVHD prior to treatment and at equivalent time points in patients without GVHD (Table 1). The median duration of follow-up was 420 days with a minimum follow-up of 180 days. Patients with veno-occlusive disease, idiopathic pneumonia syndrome, or septic shock were not included. We measured plasma levels of the 7 proteins by sequential ELISA. Logistic regression models with and without leave-one-out-cross-validation (LOOCV) tested the correlation of the laboratory values with the diagnosis of acute GVHD using area under the receiver-operating-characteristic (ROC) curves (AUC). The training set consisted of 282 randomly selected patients; the validation set included the remaining 142 patients. The final optimal fingerprint of four proteins excluded CRP because of its association with non-specific inflammation and included IL-2R-α, TNFR1, IL-8 and HGF, with AUCs of 0.91 and 0.89 in the training set (without and with LOOCV, respectively) and 0.86 in the validation set. The fingerprint had a strong association with grade of GVHD (p Figure Figure Table 1: Patients characteristics GVHD- (N=242) GVHD+ (N=182) Age-yr Median (range) 45 (1–69) 49 (1–71) Donor type (%) MRD: 169 (70%) MRD: 105 (58%) URD: 73 (30%) URD: 77 (42%) Conditioning regimen Intensity (%) Full: 182 (75%) Full: 114 (63%) Reduced: 60 (25%) Reduced: 68 (37%) Day after BMT of samples : median (range) 30 (7–104) 29 (5–119) Grade at GVHD Onset (%) Grade 0 Grade 1 Grade 2 Grade 3–4 242 (57%) 48 (12%) 100 (24%) 34 (7%) Organ Target at GVHD Onset (%) n/a Skin Gut Liver Combined 119 (65%) 38 (21%) 7 (4%) 18 (10%)
- Published
- 2007
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