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

Abstract

<b>BACKGROUND.</b> 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. <b>METHODS.</b> 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 (<i>n</i> = 309) and validation set (<i>n</i> = 358). <b>RESULTS.</b> 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 (<i>P</i> < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, <i>P</i> < 0.001) and the multicenter validation set (26% vs. 10%, <i>P</i> < 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%, <i>P</i> < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, <i>P</i> < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. <b>CONCLUSION.</b> 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. <b>FUNDING.</b> The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.