Acute graft-versus-host disease (aGvHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Steroid-resistant aGvHD is associated with poor outcome, and no commonly accepted salvage therapy is available for its treatment. Here, we report 58 adult patients treated with mesenchymal stromal cells (MSCs) as salvage therapy for steroid-refractory aGvHD. Third-party MSCs expanded in platelet lysate-containing medium were transfused at a median dose of 0.99 3 10 6 cells per kg b.wt. A median of two MSC infusions were administered to each patient. Median time between the onset of aGvHD and the first infusion of MSCs was 12 days (range, 6-62 days). Most patients (79%) had grade IV aGvHD. Five patients showed complete response, five showed very good partial response, 17 showed partial response, and 31 showed no response. The estimated probability of survival after 1 year was 19%, and median survival was 69 days. Overall survival was not significantly different from that of a historical cohort of patients receiving alternative salvage therapy and no MSC infusions. In conclusion, MSC treatment on top of conventional immunosuppression was associated with an overall response rate of 47% but improved outcome in terms of survival remains to be shown. STEM CELLS 2016;34:357-366
SIGNIFICANCE STATEMENTAcute graft versus host disease is a severe and potential life threatening complication after stem cell transplantation. Currently, corticosteroids comprise the only accepted general firstline therapy for acute and chronic GvHD, and there is no established second-line therapy. Steroid-refractoriness is associated with a dismal outcome. Mesenchymal stromal cells have been introduced as a clinical cell-based treatment option for steroid-refractory acute GvHD and conflicting results, mainly involving small patient numbers, have been published. We report the updated results of our experience with MSCs for treating steroid-refractory acute GvHD comprising one of the largest and homogenous cohort of patients.