PREDICTIVE VALUE OF CLINICAL FINDINGS AND PLASMA BIOMARKERS AFTER 14 DAYS OF PREDNISONE TREATMENT FOR ACUTE GRAFT-VERSUS-HOST DISEASE

摘要

We examined the hypothesis that plasma biomarkers and concomitant clinical findings after initial glucocorticoid therapy can accurately predict failure of graft-versus-host-disease treatment and mortality. We analyzed plasma samples and clinical data in 165 patients after 14 days of glucocorticoid therapy and used logistic regression and areas under receiver-operating characteristic curves (AUC) to evaluate associations with treatment failure and non-relapse mortality (NRM). Initial treatment of GVHD was unsuccessful in 49 patients (30%). For predicting GVHD treatment failure, the best clinical combination (total serum bilirubin and skin GVHD stage, AUC 0.70) was competitive with the best biomarker combination (TIM3 and ST2, AUC 0.73). The combination of clinical features and biomarker results offered only a slight improvement (AUC 0.75). For predicting NRM at 1 year, the best clinical predictor (total serum bilirubin, AUC 0.81) was competitive with the best biomarker combination (TIM3 and sTNFR1, AUC 0.85). The combination offered no improvement (AUC 0.85). Infection was the proximate cause of death in virtually all patients.We conclude that after 14 days of glucocorticoid therapy, clinical findings (serum bilirubin, skin GVHD) and plasma biomarkers (TIM3, ST2, sTNFR1) can predict failure of GVHD treatment and non-relapse mortality. These biomarkers reflect counter-regulatory mechanisms and provide insight into the pathophysiology of GVHD reactions following glucocorticoid treatment. The best predictive models, however, exhibit inadequate positive predictive values for identifying high-risk GVHD cohorts for investigational trials, as only a minority of patients with high-risk GVHD would be identified, and most patients would be falsely predicted to have adverse outcomes.