title: Treatment of severe steroid resistant acute GVHD with mesenchymal stromal cells (MSC).
abstract: BACKGROUND
  Several studies revealed that MSC from human bone marrow can downregulate graft-versus-host disease (GVHD) after allogeneic HSCT.
  
  
  METHODS
  Herein we present 50 patients with acute GVHD who got 74 (1-4) MSC infusions for 54 separate episodes of aGVHD.
  
  
  RESULTS
  aGVHD was defined as steroid resistant grade IV aGVHD in 42 cases. The major presentation was gastrointestinal GVHD; two (n=18) or more (n=21) systems were involved in the majority of cases. The 1(st) infusion with MSC was given on day +27 (range, 1 to 136); d+45 (range, +11 to +150) post diagnosis of aGVHD and HSCT, respectively. In 2/3 of the cases treatment was performed with frozen stocked MSCs; in 62 cases early passages (1-3) were used. The median number of infused cells was 1.14±0.47 million per kg in the first injection and up to 4.27 (1.70±1.10) millions in total. The two patients with aggressive liver GVHD received MSCs injections intra hepatic arteries without changes of blood flow or evidence cytolysis, but also without a visible effect. Disease free survival at 3.6 years was 56%. We observed better overall survival in patients with GVHD grade < 4, in responders to the 1(st) treatment with MSC, and in pediatric group. The multivariate analysis demonstrated independent influence on survival of initial response and younger age. There were no immediate or late toxicity or side effects.
  
  
  CONCLUSIONS
  Injection of MSCs seems to be a promising and safe treatment of GVHD. The encouraging results obviously should be confirmed in a randomized prospective study.
authors.affiliation: Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center Jerusalem.
authors.forename: Igor B
authors.initials: IB
authors.lastname: Resnick
authors.forename: Claudine
authors.initials: C
authors.lastname: Barkats
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shapira
authors.forename: Polina
authors.initials: P
authors.lastname: Stepensky
authors.forename: Allan I
authors.initials: AI
authors.lastname: Bloom
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: David
authors.initials: D
authors.lastname: Mankuta
authors.forename: Nira
authors.initials: N
authors.lastname: Varda-Bloom
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Rheingold
authors.forename: Moshe
authors.initials: M
authors.lastname: Yeshurun
authors.forename: Bella
authors.initials: B
authors.lastname: Bielorai
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
authors.forename: Tsila
authors.initials: T
authors.lastname: Zuckerman
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
keywords: Mesenchymal stromal cells (MSC); graft versus host disease; hematopoietic stem cell transplantation; mesenchymal stem cells; steroid resistance