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

• Published in: British journal of haematology 2013-11, Vol.163 (4), p.501-509
• Main Authors: Ball, Lynne M., Bernardo, Maria E., Roelofs, Helene, Tol, Maarten J. D., Contoli, Benedetta, Zwaginga, Jaap Jan, Avanzini, Maria Antonia, Conforti, Antonella, Bertaina, Alice, Giorgiani, Giovanna, Jol‐van der Zijde, Cornelia M., Zecca, Marco, Le Blanc, Katarina, Frassoni, Francesco, Egeler, Rudolph Maarten, Fibbe, Willem E., Lankester, Arjan C., Locatelli, Franco
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Biological and medical sciences; Child; Child, Preschool; Cohort Studies; Female; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Graft vs Host Disease - surgery; haematopoietic stem cell transplantation in children; Hematologic and hematopoietic diseases; Hematologic Neoplasms - immunology; Hematologic Neoplasms - surgery; Humans; Infant; Male; Medical sciences; Medicin och hälsovetenskap; Mesenchymal Stem Cell Transplantation - methods; mesenchymal stromal cells; Mesenchymal Stromal Cells - physiology; Neoplasm Grading; Remission Induction; Steroids - administration & dosage; steroid‐refractory acute graft‐versus‐host disease; transplantation‐related mortality; Tumors
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.12545

Summary 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.