1. MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD.
- Author
-
Major-Monfried H, Renteria AS, Pawarode A, Reddy P, Ayuk F, Holler E, Efebera YA, Hogan WJ, Wölfl M, Qayed M, Hexner EO, Wudhikarn K, Ordemann R, Young R, Shah J, Hartwell MJ, Chaudhry MS, Aziz M, Etra A, Yanik GA, Kröger N, Weber D, Chen YB, Nakamura R, Rösler W, Kitko CL, Harris AC, Pulsipher M, Reshef R, Kowalyk S, Morales G, Torres I, Özbek U, Ferrara JLM, and Levine JE
- Subjects
- Adolescent, Adrenal Cortex Hormones pharmacology, Adult, Aged, Biomarkers blood, Child, Child, Preschool, Graft vs Host Disease blood, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Infant, Middle Aged, Pancreatitis-Associated Proteins blood, Prognosis, Transplantation, Homologous adverse effects, Treatment Outcome, Young Adult, Adrenal Cortex Hormones therapeutic use, Drug Resistance, Graft vs Host Disease diagnosis, Graft vs Host Disease drug therapy, Interleukin-1 Receptor-Like 1 Protein blood
- Abstract
Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n = 236) and 2 validation cohorts separated in time (n = 142 and n = 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3α) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS ( P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P = .004) and for Minnesota risk (0.72, P = .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies., (© 2018 by The American Society of Hematology.)
- Published
- 2018
- Full Text
- View/download PDF