• Bachanova, Veronika
• Brunstein, Claudio G.
• Miller, Jeffrey S.
• Rashidi, Armin
• Ustun, Celalettin
• Slungaard, Arne
• Weisdorf, Daniel
• Warlick, Erica D.
• Gandhi, Isha
• Macmillan, Margaret L.
• Blazar, Bruce R.
• Betts, Brian C.
• Shabaneh, Ashraf
• Vercellotti, Gregory M.
• Hoeschen, Andrea L.
• Jurdi, Najla El
• Cao, Qing
• He, Fiona
• Jacobson, Pamala Ann
• Arora, Mukta
• Panoskaltsis-Mortari, Angela
• Wagner, John E.
• Wang, Jinhua

Abstract

<jats:title>Abstract</jats:title><jats:p>Acute graft-versus-host disease (aGVHD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation that fails to improve with intense immunosuppression in some patients. We hypothesized that urinary-derived human chorionic gonadotropin (uhCG) could help facilitate resolution of life-threatening aGVHD when added as supportive care via 2 potential mechanisms: immunomodulation (akin to its role in pregnancy) and supplementation of epidermal growth factor (EGF; to aid in epithelial repair). In a phase 1 study, 26 participants received subcutaneous injections of uhCG in addition to standard immunosuppression (13 receiving initial therapy for high-risk aGVHD [according to the Minnesota criteria] and 13 receiving second-line therapy). Participants underwent serial blood testing for biomarkers of hormone response, immune modulation, and aGVHD activity on study. uhCG was well tolerated, with no dose-limiting toxicities. Sixty-two percent of patients in the high-risk cohort and 54% of patients in the second-line cohort had a complete response at study day 28. Plasma EGF was elevated sixfold (from 4 to 24 pg/mL; P = .02) at 6 hours postdose in the high-risk cohort, in contrast to no peak in plasma EGF in the more severe second-line cohort. After 1 week of uhCG, patients reported a twofold increase in the regulatory T cell to conventional T-cell ratio, suggesting immune modulation despite high-dose steroids. Responding patients reported significantly lower plasma amphiregulin and higher plasma butyrate levels at study completion, suggesting improvement in mucosal damage over time. uhCG is a novel, safe, supportive therapy, proceeding to phase 2 testing at 2000 units/m2 in high-risk aGVHD. This study was registered at www.clinicaltrials.gov as #NCT02525029.</jats:p>

Topics

• impedance spectroscopy
• phase