MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

Hannah Major-Monfried, Anne S. Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A. Efebera, William J. Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O. Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J. Hartwell, Mohammed S. Chaudhry, Mina Aziz, Aaron Etra, Gregory A. YanikNicolaus Kröger, Daniela Weber, Yi Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L. Kitko, Andrew C. Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L.M. Ferrara, John E. Levine

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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 5 236) and 2 validation cohorts separated in time (n 5 142 and n 5 129). 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 REG3a) 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 5 .004) and for Minnesota risk (0.72, P 5 .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. (Blood. 2018;131(25):2846-2855)

Original languageEnglish (US)
Pages (from-to)2846-2855
Number of pages10
JournalBlood
Volume131
Issue number25
DOIs
StatePublished - Jun 21 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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