Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Chronic graft-versus host disease (GvHD) affects approximately 30%-70% of patients undergoing hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that is often used as a second-line therapeutic option for steroid-resistant chronic GvHD. There is a several week delay between the onset of ECP and clinical improvement in symptoms. Thus, a biomarker that precedes improvement in disease activity or predicts response to therapy would be of clinical value. In this study, we sought to determine how previously studied GvHD biomarkers change over a course of ECP therapy. Seven chronic GvHD biomarkers (ST2, MMP-3, CXCL9, CXCL10, CXCL11, BAFF, and CD163) were measured by ELISA in 16 patients before and after 2 months of ECP. Initial ST2 levels were high compared to healthy donors and patient samples required more than the manufacturer-recommended dilution. The median ST2 level decreased over the first 2 months of treatment (193 v. 96 ng/mL, P = 0.03); the other biomarkers did not change significantly. Serial ST2 levels at 2, 4, and 6 months after ECP initiation showed that ST2 levels declined over the course of therapy. The results of this study show that ST2 is substantially elevated and declines during therapy in patients who receive ECP as a second-line therapy for chronic GvHD.