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 - Funding Information:
The authors thank the patients, their families, and the research staff for their participation. This work was supported by grants from the National Institutes of Health, National Cancer Institute (R21CA173459, P01CA03942, and P30CA196521), an American Cancer Society Clinical Research Professorship (J.L.M.F.), and a Doris Duke Charitable Foundation Clinical Research Mentorship (M.J.H.).
Funding Information:
This work was supported by grants from the National Institutes of Health, National Cancer Institute (R21CA173459, P01CA03942, and P30CA196521), an American Cancer Society Clinical Research Professorship (J.L.M.F.), and a Doris Duke Charitable Foundation Clinical Research Mentorship (M.J.H.).
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 -