An early-biomarker algorithm predicts lethal graft-versus-host disease and survival

Matthew J Hartwell, Umut Özbek, Ernst Holler, Anne S Renteria, Hannah Major-Monfried, Pavan Reddy, Mina Aziz, William J Hogan, Francis Ayuk, Yvonne A Efebera, Elizabeth O Hexner, Udomsak Bunworasate, Muna Qayed, Rainer Ordemann, Matthias Wölfl, Stephan Mielke, Attaphol Pawarode, Yi-Bin Chen, Steven Devine, Andrew C HarrisMadan Jagasia, Carrie L Kitko, Mark R Litzow, Nicolaus Kröger, Franco Locatelli, George Morales, Ryotaro Nakamura, Ran Reshef, Wolf Rösler, Daniela Weber, Kitsada Wudhikarn, Gregory A Yanik, John E Levine, James L M Ferrara

Research output: Contribution to journalArticle

Abstract

BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set (n = 309) and validation set (n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group (P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.

Original languageEnglish
Pages (from-to)e89798
JournalOpen Insight
Volume2
Issue number3
DOIs
Publication statusPublished - Feb 9 2017

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    Hartwell, M. J., Özbek, U., Holler, E., Renteria, A. S., Major-Monfried, H., Reddy, P., Aziz, M., Hogan, W. J., Ayuk, F., Efebera, Y. A., Hexner, E. O., Bunworasate, U., Qayed, M., Ordemann, R., Wölfl, M., Mielke, S., Pawarode, A., Chen, Y-B., Devine, S., ... Ferrara, J. L. M. (2017). An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. Open Insight, 2(3), e89798. https://doi.org/10.1172/jci.insight.89798