Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study

Steroid-refractory acute graft versus host disease (AGVHD) and chronic graft versus host disease (CGVHD) after allogeneic haematopoietic stem cell transplantation are major causes of morbidity and mortality. We undertook a phase I trial in patients with steroid-refractory AGVHD and CGVHD utilising bone marrow-derived mesenchymal stromal cells (MSC). Additionally, all refractory patients were treated with etanercept concomitantly. The primary end point was safety, and secondary end points were best response achieved and overall survival. A median of two infusions per patient were administered. The response rate overall for AGVHD was complete in seven, partial in four and no response in one patient. Of the seven patients who achieved a complete response, six are alive. The actuarial survival for the overall group of AGVHD was 55% at 30 months. Two patients with CGVHD achieved complete response with two partial responses and three with no response. The survival for those with AGVHD who achieved a complete response compared with those who did not was significant (p = 0.03). We identified no early or late safety issues in the nineteen patients. In view of the poor outlook for steroid-refractory AGVHD, further trials are warranted of MSC with steroid therapy, at the onset of AGVHD before steroid resistance.