The Lancet (British edition), 2008, Vol.371 (9624), p.1579-1586
Summary 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. Funding Swedish Cancer Society, Children's Cancer Foundation, Swedish Research Council, Cancer Society in Stockholm, Cancer and Allergy Foundation, Karolinska Institutet, Istituto Superiore di Sanità, European Union, Regione Lombardia, Fondazione CARIPLO, Associazione Italiana Ricerca contro il Cancro, Compagnia di San Paolo Torino, Progetto CARIGE Cellule Staminali, European Commission, Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Ricerca Finalizzata Regione Liguria 2005 Assistenza Domiciliare, Dutch Programme for Tissue Engineering.
Internal Medicine ; Graft vs Host Disease - classification ; Graft vs Host Disease - therapy ; Severity of Illness Index ; Follow-Up Studies ; Histocompatibility Testing ; Humans ; Middle Aged ; Male ; Survival Rate ; Treatment Outcome ; Transplantation, Homologous ; Neoplasms - therapy ; Graft vs Host Disease - mortality ; Immunotherapy ; Hematopoietic Stem Cell Transplantation - adverse effects ; Adult ; Female ; Transplantation Conditioning - methods ; Child ; Mesenchymal Stem Cell Transplantation ; Complications and side effects ; Care and treatment ; Usage ; Stem cells ; Graft versus host reaction ; Transplantation ; Research ; Health aspects ; Risk factors ; Hematopoietic stem cells ; Index Medicus ; Abridged Index Medicus ; Medicin och hälsovetenskap
Backfile Package - All of Back Files EBS [ALLOFBCKF]
© ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
Permalink to record