title: Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients.
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.
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy. Electronic address: mintrona@hpg23.it.
authors: Martino
authors: M
authors: Introna
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Giovanna
authors: G
authors: Lucchini
authors: HSCT Pediatric Unit, "M. Tettamanti" Research Centre, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Erica
authors: E
authors: Dander
authors: Department of Health Sciences, Center of Biostatistics for Clinical Epidemiology, University of Milan-Bicocca, Monza, Italy.
authors: Stefania
authors: S
authors: Galimberti
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Attilio
authors: A
authors: Rovelli
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Adriana
authors: A
authors: Balduzzi
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Daniela
authors: D
authors: Longoni
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Fabio
authors: F
authors: Pavan
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Francesca
authors: F
authors: Masciocchi
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Alessandra
authors: A
authors: Algarotti
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Caterina
authors: C
authors: Micò
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Anna
authors: A
authors: Grassi
authors: Divisione di Ematologia e TMO, Ospedale Generale di Bolzano, Bolzano, Italy.
authors: Sara
authors: S
authors: Deola
authors: Divisione di Ematologia e TMO, Ospedale Generale di Bolzano, Bolzano, Italy.
authors: Irene
authors: I
authors: Cavattoni
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Giuseppe
authors: G
authors: Gaipa
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Daniela
authors: D
authors: Belotti
authors: Immunotransfusion Unit, San Gerardo Hospital, Monza, Italy.
authors: Paolo
authors: P
authors: Perseghin
authors: HSCT Adult Unit, San Gerardo Hospital, Monza, Italy.
authors: Matteo
authors: M
authors: Parma
authors: HSCT Adult Unit, San Gerardo Hospital, Monza, Italy.
authors: Enrico
authors: E
authors: Pogliani
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Josee
authors: J
authors: Golay
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Olga
authors: O
authors: Pedrini
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Chiara
authors: C
authors: Capelli
authors: Divisione di Ematologia e TMO, Ospedale Generale di Bolzano, Bolzano, Italy.
authors: Sergio
authors: S
authors: Cortelazzo
authors: HSCT Pediatric Unit, "M. Tettamanti" Research Centre, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Giovanna
authors: G
authors: D'Amico
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Andrea
authors: A
authors: Biondi
authors: Division of Hematology and Laboratory of Cell Therapy "G. Lanzani", Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors: Alessandro
authors: A
authors: Rambaldi
authors: HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.
authors: Ettore
authors: E
authors: Biagi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D013256:Steroids
keywords: Cell therapy; Hematopoietic stem cell transplantation (HSCT); Immunosuppressive treatment; Mesenchymal stromal cells; Steroid refractory graft-versus-host disease (GVHD)