Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease

Mesenchymal stromal cell (MSC) infusions have been reported to be effective in patients with steroid-refractory, acute graft-versus-host disease (aGvHD) but comprehensive data on paediatric patients are limited. We retrospectively analysed a cohort of 37 children (aged 3months-17years) treated with MSCs for steroid-refractory grade III-IV aGvHD. All patients but three received multiple MSC infusions. Complete response (CR) was observed in 24 children (65%), while 13 children had either partial (n=8) or no response (n=5). Cumulative incidence of transplantation-related mortality (TRM) in patients who did or did not achieve CR was 17% and 69%, respectively (P=0001). After a median follow-up of 29years, overall survival (OS) was 37%; it was 65% vs. 0% in patients who did or did not achieve CR, respectively (P=0001). The median time from starting steroids for GvHD treatment to first MSC infusion was 13d (range 5-85). Children treated between 5 and 12d after steroid initiation showed a trend for better OS (56%) and lower TRM (17%) as compared with patients receiving MSCs 13-85d after steroids (25% and 53%, respectively; P=022 and 006, respectively). Multiple MSC infusions are safe and effective for children with steroid-refractory aGvHD, especially when employed early in the disease course.