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Anasayfa : Haberler : Steroide Dirençli Akut GVHH'de Mezenkimal Kök Hücre Tedavisi

Steroide Dirençli Akut GVHH'de Mezenkimal Kök Hücre Tedavisi

Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study

 


Prof Katarina Le Blanc MDa, Corresponding Author Contact Information, E-mail The Corresponding Author, Francesco Frassoni MDb, , Lynne Ball MDd, , Prof Franco Locatelli MDf, Helene Roelofs PhDe, Ian Lewis MDg, Edoardo Lanino MDc, Berit Sundberg BSca, Maria Ester Bernardo MDf, Mats Remberger PhDa, Giorgio Dini MDc, Prof R Maarten Egeler MDd, Andrea Bacigalupo MDb, Prof Willem Fibbe MDe, Prof Olle Ringdén MDa and on behalf of the Developmental Committee of the European Group for Blood and Marrow Transplantation
 

Refers to: Mesenchymal stem cells as cellular immunosuppressants
The Lancet, Volume 371, Issue 9624, 10 May 2008-16 May 2008, Pages 1553-1554
Dominik Wolf, Anna Maria Wolf
PDF (124 K)
 

Background
Severe graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic transplantation with haemopoietic stem cells. Mesenchymal stem cells modulate immune responses in vitro and in vivo. We aimed to assess whether mesenchymal stem cells could ameliorate GVHD after haemopoietic-stem-cell transplantation.
Methods
Patients with steroid-resistant, severe, acute GVHD were treated with mesenchymal stem cells, derived with the European Group for Blood and Marrow Transplantation ex-vivo expansion procedure, in a multicentre, phase II experimental study. We recorded response, transplantation-related deaths, and other adverse events for up to 60 months' follow-up from infusion of the cells.
Findings
Between October, 2001, and January, 2007, 55 patients were treated. The median dose of bone-marrow derived mesenchymal stem cells was 1·4×106 (min–max range 0·4–9×106) cells per kg bodyweight. 27 patients received one dose, 22 received two doses, and six three to five doses of cells obtained from HLA-identical sibling donors (n=5), haploidentical donors (n=18), and third-party HLA-mismatched donors (n=69). 30 patients had a complete response and nine showed improvement. No patients had side-effects during or immediately after infusions of mesenchymal stem cells. Response rate was not related to donor HLA-match. Three patients had recurrent malignant disease and one developed de-novo acute myeloid leukaemia of recipient origin. Complete responders had lower transplantation-related mortality 1 year after infusion than did patients with partial or no response (11 [37%] of 30 vs 18 [72%] of 25; p=0·002) and higher overall survival 2 years after haemopoietic-stem-cell transplantation (16 [53%] of 30 vs four [16%] of 25; p=0·018).
Interpretation
Infusion of mesenchymal stem cells expanded in vitro, irrespective of the donor, might be an effective therapy for patients with steroid-resistant, acute GVHD.

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