title: Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid-refractory, grade III-IV acute graft-versus-host disease.
abstract: 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 3 months-17 years) 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 = 0.001). After a median follow-up of 2.9 years, overall survival (OS) was 37%; it was 65% vs. 0% in patients who did or did not achieve CR, respectively (P = 0.001). The median time from starting steroids for GvHD treatment to first MSC infusion was 13 d (range 5-85). Children treated between 5 and 12 d after steroid initiation showed a trend for better OS (56%) and lower TRM (17%) as compared with patients receiving MSCs 13-85 d after steroids (25% and 53%, respectively; P = 0.22 and 0.06, respectively). Multiple MSC infusions are safe and effective for children with steroid-refractory aGvHD, especially when employed early in the disease course.
authors.affiliation: Department of Paediatrics, Stem Cell Transplantation Unit, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ball
authors.forename: Maria E
authors.initials: ME
authors.lastname: Bernardo
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Benedetta
authors.initials: B
authors.lastname: Contoli
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Zwaginga
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Avanzini
authors.forename: Antonella
authors.initials: A
authors.lastname: Conforti
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giorgiani
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Katarina
authors.initials: K
authors.lastname: Le Blanc
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Rudolph Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000601:surgery*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery; D006801:Humans; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D060787:Neoplasm Grading; D012074:Remission Induction; D013256:Steroids / Q000008:administration & dosage
chemical_list: D013256:Steroids
keywords: haematopoietic stem cell transplantation in children; mesenchymal stromal cells; steroid-refractory acute graft-versus-host disease; transplantation-related mortality