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Type: Journal article
Title: Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study
Author: Le Blanc, K.
Frassoni, F.
Ball, L.
Locatelli, F.
Roelofs, H.
Lewis, I.
Lanino, E.
Sundberg, B.
Bernardo, M.
Remberger, M.
Dini, G.
Egeler, R.
Bacigalupo, A.
Fibbe, W.
Ringden, O.
Citation: Lancet, 2008; 371(9624):1579-1586
Publisher: Lancet Ltd
Issue Date: 2008
ISSN: 0140-6736
Statement of
Katarina Le Blanc, Francesco Frassoni, Lynne Ball, Franco Locatelli, Helene Roelofs, Ian Lewis, Edoardo Lanino, Berit Sundberg, Maria Ester Bernardo, Mats Remberger, Giorgio Dini, R Maarten Egeler, Andrea Bacigalupo, Prof Willem Fibbe, Prof Olle Ringdén and on behalf of the Developmental Committee of the European Group for Blood and Marrow Transplantation
Abstract: 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 1.4x10(6) (min-max range 0.4-9x10(6)) 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.
Keywords: Developmental Committee of the European Group for Blood and Marrow Transplantation; Humans; Neoplasms; Graft vs Host Disease; Histocompatibility Testing; Treatment Outcome; Immunotherapy; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Mesenchymal Stem Cell Transplantation; Transplantation, Homologous; Severity of Illness Index; Survival Rate; Follow-Up Studies; Adult; Middle Aged; Child; Female; Male
Rights: Copyright © 2008 Elsevier Ltd All rights reserved.
RMID: 0020080604
DOI: 10.1016/S0140-6736(08)60690-X
Appears in Collections:Medicine publications

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