Allogeneic Bone Marrow Mesenchymal Stromal Cell Therapy in Patients with Steroid-Refractory Graft Versus Host Disease—a Pilot Study from Pakistan

Background: Mesenchymal stromal cells (MSCs) have emerged as a promising candidate for the treatment of steroid-refractory graft-versus-host disease (GVHD). Methods: In this uncontrolled, pilot clinical study, we report safety and efficacy of allogeneic bone marrow MSCs administered intravenously to steroid-refractory GVHD patients. Results: A total of 33 MSC infusions were given to 10 patients suffering from acute GVHD (n = 3), chronic GVHD (n = 5), and overlap syndrome (n = 2). Eight out of ten patients are alive after a median follow-up of 11 months with five having sustained complete remission (CR). Three patients with partial response received further doses to sustain the response. One of them died of lung infection while others are still alive. One out of the two non-responding patients died after 17 days of MSC therapy due to advanced liver GVHD while the other is having a stable disease course. The overall and GVHD-free survival was 80% and 50%, respectively. The patients developed no complication or toxicity related to MSC infusion. Luminex analysis revealed a modest drop after MSC infusion in pro-inflammatory cytokines like TNFα, IL-1β, and IL-6 whereas serum IL-10 levels were slightly raised. Conclusion: Allogeneic donor-derived bone marrow mesenchymal stromal cell therapy is a safe and feasible treatment for steroid-refractory GVHD patients (NCT02824653). Lay Summary: We report the safety and efficacy of allogeneic bone marrow mesenchymal stromal cell therapy in 10 patients suffering from steroid-resistant graft-versus-host disease. Eight out of ten patients are alive after a median follow-up of 11 months with five having sustained CR. The response rate was better in acute GVHD patients compared to chronic GVHD patients. MSC therapy within 20 days of steroid-refractory acute GVHD resulted in sustained CR. Initial and sustained response was superior in pediatric patients compared to adults. The Luminex analysis showed a modest decrease in pro-inflammatory cytokines in those responding to MSC therapy.