Clinical outcomes in children with steroid-refractory acute graft-versus-host disease (SR-aGVHD) are generally poor with a high mortality rate and limited therapeutic options. We report here our updated investigational experience with mesenchymal stromal cell therapy (remestemcel-L) used in a multicenter expanded access protocol (NCT00759018) in 241 children with aGVHD who failed to respond to steroids with or without other secondary and
tertiary immunosuppressive therapies (IST). A total of 241 children with Grade B-D steroid refractory (SR) aGVHD were enrolled in 50 sites in eight countries and received eight biweekly intravenous infusions of human mesenchymal stromal cells (hMSCs) 2x10(6) per kg for four weeks, with an option for an additional four weekly infusions after day 28 for subjects who achieved either a partial or mixed response. Mean age of subjects was 9.6 years; 39% were female, and 60% were white. Most of the subjects had grade C (30%) or grade D (50%) disease and in most cases, the subjects had failed to respond to other immunosuppressive agents after failing steroids. The primary endpoint was overall response rate (ORR, the sum of complete and partial response) at day 28. Across all subjects, the 28 day ORR, was observed in n=157 (65.1%) with 34 (14.1%) and 123 (51.3%) achieving complete and partial responses, respectively. Stratified by aGVHD grade at baseline, the rate of overall response at day 28 was 72.9% for aGVHD grade B, 67.1% for grade C, and 60.8% for grade D subjects. Survival through day 100, a secondary endpoint of the study was 66.9% (n=160/239). Importantly, survival through day 100 was significantly greater in subjects that achieved a day 28 OR (82.1%) compared with non-responders (38.6%), log rank p<0.001. Remestemcel-L safety was generally well tolerated with no infusional toxicity and no identified safety concerns. In summary, this update to the remestemcel-L EAP confirms the reported clinical and survival benefits of remestemcel-L therapy in children with aGVHD who have exhausted all conventional therapeutic options.