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

Major-Monfried H, Renteria AS, Pawarode A, Reddy P, Ayuk F, Holler E, Efebera YA, Hogan WJ, Woelfl M, Qayed M, Hexner EO, Wudhikarn K, Ordemann R, Young R, Shah J, Hartwell MJ, Chaudhry M, Aziz M, Etra A, Yanik GA, Kroeger N, Weber D, Chen YB, Nakamura R, Rösler W, Kitko CL, Harris AC, Pulsipher M, Reshef R, Kowalyk S, Morales G, Torres I, Ozbek U, Ferrara JLM, Levine JE (2018)

Publication Type: Journal article

Publication year: 2018

Journal

DOI: 10.1182/blood-2018-01-822957

Abstract

Acute graft versus host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after one week of therapy often guides further treatment decisions, but long term outcomes vary widely between centers and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken after one week of systemic treatment for GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into test (n=236) and two validation cohorts separated in time (n = 142 and 129, respectively). Initial response to systemic steroids correlated with response at four weeks, one-year non-relapse mortality (NRM) and overall survival (OS). A previously validated algorithm of two MAGIC biomarkers (ST2 and REG3α) consistently separated steroid resistant patients into two groups with dramatically different NRM and OS (p<0.001 for all three 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 curves showed the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, p=0.004) and for Minnesota risk (0.72, p=0.005). In conclusion, MAGIC biomarker probabilities generated after one week of systemic treatment for GVHD predict long term outcomes in steroid resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies.

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) University of Michigan United States (USA) (US) Universitätsklinikum Heidelberg Germany (DE) Universität Regensburg Germany (DE) Ohio State University United States (USA) (US) Mayo Clinic United States (USA) (US) Julius-Maximilians-Universität Würzburg Germany (DE) Emory University United States (USA) (US) University of Pennsylvania United States (USA) (US) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH) Technische Universität Dresden Germany (DE) Massachusetts General Hospital United States (USA) (US) City of Hope Medical Center United States (USA) (US) Vanderbilt University United States (USA) (US) University of Utah United States (USA) (US) Children's Hospital Los Angeles United States (USA) (US) Columbia University United States (USA) (US)

How to cite

APA:

Major-Monfried, H., Renteria, A.S., Pawarode, A., Reddy, P., Ayuk, F., Holler, E.,... Levine, J.E. (2018). MAGIC biomarkers predict long term outcomes for steroid-resistant acute GVHD. Blood. https://dx.doi.org/10.1182/blood-2018-01-822957

MLA:

Major-Monfried, Hannah, et al. "MAGIC biomarkers predict long term outcomes for steroid-resistant acute GVHD." Blood (2018).

BibTeX: Download