Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation.
Multipotent mesenchymal stromal cells (MSC) have immunomodulatory effects. The aim of this study was to demonstrate safety and feasibility of MSC transfusion in pediatric patients who had undergone allogeneic stem cell transplantation from MMFD, MUD, MMUD and MSD. Patients with posttransplant complications based on deregulated immune effector cells who may benefit from an immunomodulatory effect of MSC had been selected. MSC were isolated from the hematopoietic stem cell donors in five cases and from a third party parental donor in two cases. We transfused ex vivo-expanded MSC in 11 doses into seven pediatric patients. Cell doses were escalated based on availability from 0.4x10(6) to 3.0x10(6) per kg bodyweight No adverse effects were detected with a maximum follow-up of 29 months. One out of three patients showed slight improvement of chronic GVHD. Two patients with severe acute GvHD did not progress to cGvHD. One patient received MSC to stabilize graft function after secondary haploidentical transplantation. One patient recovered from trilineage failure due to severe hemophagocytosis. This is the first case of a pediatric patient treated with MSC for trilineage failure after haploidentical stem cell transplantation from her father. We report the first series of 11 transfusions of expanded MSC in pediatric patients with immunological complications after allogeneic transplantation. Transfusion of MSC was safe and encouraging improvements in some patients were observed.
Müller
Ingo
I
Department of General Pediatrics, Hematology and Oncology, University Children's Hospital Tübingen, Hoppe-Seyler-St. 1, 72076, Tubigen, Germany. Ingo.Mueller@med.uni-tuebingen.de
Kordowich
Sandra
S
Holzwarth
Christina
C
Isensee
Gesa
G
Lang
Peter
P
Neunhoeffer
Felix
F
Dominici
Massimo
M
Greil
Johann
J
Handgretinger
Rupert
R
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000601:surgery; D006086:Graft vs Host Disease / Q000601:surgery; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology; D039902:Multipotent Stem Cells / Q000276:immunology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D012086:Reoperation; D017154:Stromal Cells / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous; D016896:Treatment Outcome