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Evaluation of Elafin as a Prognostic Biomarker in Acute Graft-versus-Host Disease

•Serum elafin concentrations do not predict 6-month nonrelapse mortality (NRM), overall survival (OS), or treatment response in recipients of hematopoietic cell transplantation (HCT).•Regenerating islet-derived 3a (REG3α) and Suppressor of tumorigenesis 2 (ST2) are validated biomarkers of gastrointe...

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Published in:Transplantation and cellular therapy 2021-12, Vol.27 (12), p.988.e1-988.e7
Main Authors: Zewde, Makda Getachew, Morales, George, Gandhi, Isha, Özbek, Umut, Aguayo-Hiraldo, Paibel, Ayuk, Francis, Baez, Janna, Chanswangphuwana, Chantiya, Choe, Hannah, DeFilipp, Zachariah, Etra, Aaron, Grupp, Stephan, Hexner, Elizabeth O., Hogan, William, Javorniczky, Nora Rebeka, Kasikis, Stelios, Kitko, Carrie L., Kowalyk, Steven, Meedt, Elisabeth, Merli, Pietro, Nakamura, Ryotaro, Qayed, Muna, Reshef, Ran, Rösler, Wolf, Schechter, Tal, Weber, Daniela, Wölfl, Matthias, Yanik, Gregory, Young, Rachel, Levine, John E., Ferrara, James L.M., Chen, Yi-Bin
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Language:English
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Summary:•Serum elafin concentrations do not predict 6-month nonrelapse mortality (NRM), overall survival (OS), or treatment response in recipients of hematopoietic cell transplantation (HCT).•Regenerating islet-derived 3a (REG3α) and Suppressor of tumorigenesis 2 (ST2) are validated biomarkers of gastrointestinal graft-versus-host disease that accurately predict 6-month NRM, OS, and treatment response in HCT recipients.•The addition of elafin to REG3α and ST2 did not improve their predictive accuracy. Acute graft-versus-host disease (GVHD) is a major cause of mortality in patients undergoing hematopoietic cell transplantation (HCT) for hematologic malignancies. The skin is the most commonly involved organ in GVHD. Elafin, a protease inhibitor overexpressed in inflamed epidermis, was previously identified as a diagnostic biomarker of skin GVHD; however, this finding was restricted to a subset of patients with isolated skin GVHD. The main driver of nonrelapse mortality (NRM) in HCT recipients is gastrointestinal (GI) GVHD. Two biomarkers, Regenerating islet-derived 3a (REG3α) and Suppressor of tumorigenesis 2 (ST2), have been validated as biomarkers of GI GVHD that predict long-term outcomes in patients treated for GVHD. We undertook this study to determine the utility of elafin as a prognostic biomarker in the general population of acute GVHD patients in whom GVHD may develop in multiple organs. We analyzed serum elafin concentrations as a predictive biomarker of acute GVHD outcomes and compared it with ST2 and REG3α in a large group of patients treated at multiple centers. A total of 526 patients from the Mount Sinai Acute GVHD International Consortium (MAGIC) who had received corticosteroid treatment for skin GVHD and who had not been previously studied were analyzed. Serum concentrations of elafin, ST2, and REG3α were measured by ELISA in all patients. The patients were divided at random into equal training and validation sets, and a competing-risk regression model was developed to model 6-month NRM using elafin concentration in the training set. Additional models were developed using concentrations of ST2 and REG3α or the combination of all 3 biomarkers as predictors. Receiver operating characteristic (ROC) curves were constructed using the validation set to evaluate the predictive accuracy of each model and to stratify patients into high- and low-risk biomarker groups. The cumulative incidence of 6-month NRM, overall survival (OS), and 4-week treatment respons
ISSN:2666-6367
2666-6375
2666-6367
DOI:10.1016/j.jtct.2021.08.021