TY - JOUR
T1 - MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD
AU - Major-Monfried, Hannah
AU - Renteria, Anne S.
AU - Pawarode, Attaphol
AU - Reddy, Pavan
AU - Ayuk, Francis
AU - Holler, Ernst
AU - Efebera, Yvonne A.
AU - Hogan, William J.
AU - Wölfl, Matthias
AU - Qayed, Muna
AU - Hexner, Elizabeth O.
AU - Wudhikarn, Kitsada
AU - Ordemann, Rainer
AU - Young, Rachel
AU - Shah, Jay
AU - Hartwell, Matthew J.
AU - Chaudhry, Mohammed S.
AU - Aziz, Mina
AU - Etra, Aaron
AU - Yanik, Gregory A.
AU - Kröger, Nicolaus
AU - Weber, Daniela
AU - Chen, Yi Bin
AU - Nakamura, Ryotaro
AU - Rösler, Wolf
AU - Kitko, Carrie L.
AU - Harris, Andrew C.
AU - Pulsipher, Michael
AU - Reshef, Ran
AU - Kowalyk, Steven
AU - Morales, George
AU - Torres, Ivan
AU - Özbek, Umut
AU - Ferrara, James L.M.
AU - Levine, John E.
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/6/21
Y1 - 2018/6/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048708977&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-01-822957
DO - 10.1182/blood-2018-01-822957
M3 - Article
C2 - 29545329
AN - SCOPUS:85048708977
SN - 0006-4971
VL - 131
SP - 2846
EP - 2855
JO - Blood
JF - Blood
IS - 25
ER -