Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid‐refractory, grade <scp>III</scp>–<scp>IV</scp> acute graft‐versus‐host disease

<jats:title>Summary</jats:title><jats:p>Mesenchymal stromal cell (<jats:styled-content style="fixed-case">MSC</jats:styled-content>) infusions have been reported to be effective in patients with steroid‐refractory, acute graft‐versus‐host disease (a<jats:styled-content style="fixed-case">G</jats:styled-content>v<jats:styled-content style="fixed-case">HD</jats:styled-content>) but comprehensive data on paediatric patients are limited. We retrospectively analysed a cohort of 37 children (aged 3 months‐17 years) treated with <jats:styled-content style="fixed-case">MSC</jats:styled-content>s for steroid‐refractory grade <jats:styled-content style="fixed-case">III</jats:styled-content>–<jats:styled-content style="fixed-case">IV</jats:styled-content> a<jats:styled-content style="fixed-case">G</jats:styled-content>v<jats:styled-content style="fixed-case">HD</jats:styled-content>. All patients but three received multiple <jats:styled-content style="fixed-case">MSC</jats:styled-content> infusions. Complete response (<jats:styled-content style="fixed-case">CR</jats:styled-content>) was observed in 24 children (65%), while 13 children had either partial (<jats:italic>n </jats:italic>= 8) or no response (<jats:italic>n </jats:italic>= 5). Cumulative incidence of transplantation‐related mortality (<jats:styled-content style="fixed-case">TRM</jats:styled-content>) in patients who did or did not achieve <jats:styled-content style="fixed-case">CR</jats:styled-content> was 17% and 69%, respectively (<jats:italic>P </jats:italic>= 0·001). After a median follow‐up of 2·9 years, overall survival (<jats:styled-content style="fixed-case">OS</jats:styled-content>) was 37%; it was 65% vs. 0% in patients who did or did not achieve <jats:styled-content style="fixed-case">CR</jats:styled-content>, respectively (<jats:italic>P </jats:italic>= 0·001). The median time from starting steroids for <jats:styled-content style="fixed-case">G</jats:styled-content>v<jats:styled-content style="fixed-case">HD</jats:styled-content> treatment to first <jats:styled-content style="fixed-case">MSC</jats:styled-content> infusion was 13 d (range 5–85). Children treated between 5 and 12 d after steroid initiation showed a trend for better <jats:styled-content style="fixed-case">OS</jats:styled-content> (56%) and lower <jats:styled-content style="fixed-case">TRM</jats:styled-content> (17%) as compared with patients receiving <jats:styled-content style="fixed-case">MSC</jats:styled-content>s 13–85 d after steroids (25% and 53%, respectively; <jats:italic>P </jats:italic>= 0·22 and 0·06, respectively). Multiple <jats:styled-content style="fixed-case">MSC</jats:styled-content> infusions are safe and effective for children with steroid‐refractory a<jats:styled-content style="fixed-case">G</jats:styled-content>v<jats:styled-content style="fixed-case">HD</jats:styled-content>, especially when employed early in the disease course.</jats:p>