Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients
Martino Introna, Giovanna Lucchini, Erica Dander, Stefania Galimberti, Attilio Rovelli, Adriana Balduzzi, Daniela Longoni, Fabio Pavan, Francesca Masciocchi, Alessandra Algarotti, Caterina Micò, Anna Grassi, Sara Deola, Irene Cavattoni, Giuseppe Gaipa, Daniela Belotti, Paolo Perseghin, Matteo Parma, Enrico Pogliani, Josee Golay, Olga Pedrini, Chiara Capelli, Sergio Cortelazzo, Giovanna D'Amico, Andrea Biondi, Alessandro Rambaldi, Ettore Biagi, Martino Introna, Giovanna Lucchini, Erica Dander, Stefania Galimberti, Attilio Rovelli, Adriana Balduzzi, Daniela Longoni, Fabio Pavan, Francesca Masciocchi, Alessandra Algarotti, Caterina Micò, Anna Grassi, Sara Deola, Irene Cavattoni, Giuseppe Gaipa, Daniela Belotti, Paolo Perseghin, Matteo Parma, Enrico Pogliani, Josee Golay, Olga Pedrini, Chiara Capelli, Sergio Cortelazzo, Giovanna D'Amico, Andrea Biondi, Alessandro Rambaldi, Ettore Biagi
Abstract
This phase I multicenter study was aimed at assessing the feasibility and safety of intravenous administration of third party bone marrow-derived mesenchymal stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and 25 adults), experiencing steroid-resistant grade II to IV graft-versus-host disease (GVHD). Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy. A median cell dose of 1.5 × 10(6)/kg per infusion was administered. No acute toxicity was reported. Overall, 86 adverse events and serious adverse events were reported in the study, most of which (72.1%) were of infectious nature. Overall response rate, measured at 28 days after the last MSC injection, was 67.5%, with 27.5% complete response. The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant in children as compared with adults (46.7 versus 16.0%, P = .065). Overall survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%, with a median survival time of 1.1 years. In conclusion, MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment. Eudract Number 2008-007869-23, NCT01764100.
Keywords: Cell therapy; Hematopoietic stem cell transplantation (HSCT); Immunosuppressive treatment; Mesenchymal stromal cells; Steroid refractory graft-versus-host disease (GVHD).
Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Source: PubMed