title: Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation.
abstract: When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM.
authors.affiliation: Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. mebernardo@gmail.com
authors.forename: M E
authors.initials: ME
authors.lastname: Bernardo
authors.forename: L M
authors.initials: LM
authors.lastname: Ball
authors.forename: A M
authors.initials: AM
authors.lastname: Cometa
authors.forename: H
authors.initials: H
authors.lastname: Roelofs
authors.forename: M
authors.initials: M
authors.lastname: Zecca
authors.forename: M A
authors.initials: MA
authors.lastname: Avanzini
authors.forename: A
authors.initials: A
authors.lastname: Bertaina
authors.forename: L
authors.initials: L
authors.lastname: Vinti
authors.forename: A
authors.initials: A
authors.lastname: Lankester
authors.forename: R
authors.initials: R
authors.lastname: Maccario
authors.forename: O
authors.initials: O
authors.lastname: Ringden
authors.forename: K
authors.initials: K
authors.lastname: Le Blanc
authors.forename: R M
authors.initials: RM
authors.lastname: Egeler
authors.forename: W E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D018952:Antigens, CD34 / Q000097:blood; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D012306:Risk; D014184:Transplantation, Homologous
chemical_list: D018952:Antigens, CD34