title: Mesenchymal stromal cells for treatment of steroid-refractory GvHD: a review of the literature and two pediatric cases.
abstract: Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results.We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively).These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients.
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Wernicke
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.|Medical Life Science and Technology Center, TUM Graduate School, Technische Universität München, Boltzmannstrasse 17, 85748 Garching, Germany.
authors.forename: Thomas Gp
authors.initials: TG
authors.lastname: Grunewald
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.
authors.forename: Juenger
authors.initials: J
authors.lastname: Hendrik
authors.affiliation: Division for Stem Cell Transplantation, Department of Hematology, Oncology and Hemostasis, Hospital for Children and Adolescents, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Selim
authors.initials: S
authors.lastname: Kuci
authors.affiliation: Division for Stem Cell Transplantation, Department of Hematology, Oncology and Hemostasis, Hospital for Children and Adolescents, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Zyrafete
authors.initials: Z
authors.lastname: Kuci
authors.affiliation: Division for Stem Cell Transplantation, Department of Hematology, Oncology and Hemostasis, Hospital for Children and Adolescents, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
authors.affiliation: University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: University Children's Hospital, Hoppe-Seyler-Strasse 1, 72076 Tuebingen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Doering
authors.affiliation: St. Anna Children's Hospital, Kinderspitalgasse 6, 1090 Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.affiliation: St. Anna Children's Hospital, Kinderspitalgasse 6, 1090 Vienna, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Lawitschka
authors.affiliation: Division for Stem Cell Transplantation, Department of Medicine III, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
authors.affiliation: Division for Stem Cell Transplantation, Department of Hematology, Oncology and Hemostasis, Hospital for Children and Adolescents, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.affiliation: Children's Cancer Research and Roman Herzog Comprehensive Cancer Center, Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Kölner Platz 1, 80804 Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: von Luettichau