Adoptive Transfer of Regulatory T Cells in Pediatric Patients with Treatment-Refractory Acute Graft-versus-Host Disease

Severe Graft-versus-Host Disease can be effectively controlled by adoptive transfer of Regulatory T cells preceded by lymphodepletion. In refractory Graft-versus-Host Disease Regulatory T cell transfer can provide a safe alternative to induce long-term disease-control. Despite advancements in donor selection, conditioning regimens, and immunosuppressive therapies, graft-versus-host disease (GvHD) remains a frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT). Regulatory T cells (Tregs), key mediators of immune tolerance, have been investigated for use in GvHD, with promising preclinical and early clinical data. Here we report two pediatric HSCT recipients who underwent successful adoptive Treg therapy for severe, treatment-refractory acute GvHD.In both patients, conventional GvHD therapy in the form of immunosuppression, including calcineurin inhibitors, ruxolitinib, and extracorporeal photopheresis, did not achieve disease control. Both patients experienced life-threatening disease progression refractory to all conventional therapy. Tregs were isolated from original stem cell donors and administered following lymphodepletion. Patient 1 achieved partial remission of intestinal GvHD after initial Treg infusion, with sustained response following multiple doses, allowing for long-term immunosuppressant tapering. Patient 2 showed substantial improvement in cutaneous GvHD after repeated Treg infusions. Complete remission was achieved and immunosuppression successfully discontinued.These findings support the feasibility, safety, and efficacy of adoptive Treg therapy in refractory GvHD. Long-term GvHD control without significant infusion-related complications highlight the potential of Tregs as a potent GvHD-directed therapy.