Outcomes of Etanercept Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease in Adult and Pediatric Patients: A Retrospective Single-Center Cohort Study

Steroid-refractory acute graft-versus-host disease (SR-aGvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (alloHSCT), particularly in grade III–IV cases. While ruxolitinib is the only approved second-line therapy for patients aged 12 and older, its limited efficacy and lack of approval for younger children underscore the need for alternatives. Etanercept (ET), a TNF-alpha inhibitor, has been used off-label for SR-aGvHD, but age-stratified data are limited. In this retrospective single-center study, we analyzed outcomes of 103 patients with grade III–IV SR-aGvHD treated with either ET or best available therapy (BAT) at Hadassah Medical Center. Pediatric patients had significantly better overall survival (OS) and event-free survival (EFS) than adults (p < 0.0001). Among ET-treated patients, children had a 71% response rate versus 6.7% in adults. ET use in pediatric patients was associated with improved survival over BAT (p < 0.05), while adults showed a non-significant trend toward worse outcomes (p = 0.085). Infection was the leading cause of death across all groups, though ET was not linked to increased infection-related mortality. These findings support ET as a potentially effective and safe salvage therapy in pediatric SR-aGvHD, with limited benefit in adults. Prospective studies are needed to refine age-specific treatment strategies.