title: Sequential third-party mesenchymal stromal cell therapy for refractory acute graft-versus-host disease.
abstract: We evaluated the feasibility, safety, and efficacy of the administration of 4 sequential doses (intravenously administered on days 1, 4, 11, and 18) of cryopreserved bone marrow-derived mesenchymal stromal cells (MSC) expanded with platelet lysate and obtained from third-party donors as a second-line treatment for steroid-refractory acute graft-versus-host (aGVHD) disease in a series of 25 patients. All patients received at least 2 doses of MSC, whereas 21 received 3 doses and 18 received the initially planned 4 doses. Because of the achievement of partial response, 4 patients received additional doses of MSC. Median single cell dose administered was 1.1 × 10(6) MSC/kg of recipient body weight. There were no adverse events related to the MSC infusion in the 99 procedures performed, with the exception of a cardiac ischemic event that occurred twice in a patient with prior history of cardiac ischemia. Response to MSC at 60 days after the first dose was evaluable in 24 patients. Seventeen patients (71%) responded (11 complete and 6 partial responses), with a median time to response of 28 days after the first MSC dose, whereas 7 patients did not respond. In summary, we can conclude that sequential cryopreserved third-party MSC therapy administered on days 1, 4, 11, and 18 is a safe procedure for patients with steroid-refractory aGVHD. This strategy may provide a high rate of overall responses of aGVHD with a low toxicity profile.
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain; Red Nacional de Terapia Celular (TerCel), ISCIII, Spain.
authors: Fermín
authors: F
authors: Sánchez-Guijo
authors: Servicio de Hematología, Instituto de biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors: Teresa
authors: T
authors: Caballero-Velázquez
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain; Red Nacional de Terapia Celular (TerCel), ISCIII, Spain.
authors: Olga
authors: O
authors: López-Villar
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain; Red Nacional de Terapia Celular (TerCel), ISCIII, Spain.
authors: Alba
authors: A
authors: Redondo
authors: Servicio de Hematología, Instituto de biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors: Rocío
authors: R
authors: Parody
authors: Servicio de Hematología, Hospital Clinic, Barcelona, Spain.
authors: Carmen
authors: C
authors: Martínez
authors: Servicio de Hematología, Hospital de Navarra, Pamplona, Spain.
authors: Eduardo
authors: E
authors: Olavarría
authors: Red Nacional de Terapia Celular (TerCel), ISCIII, Spain; Servicio de Hematología, Clínica Universidad de Navarra, Pamplona, Spain.
authors: Enrique
authors: E
authors: Andreu
authors: Red Nacional de Terapia Celular (TerCel), ISCIII, Spain; Servicio de Hematología, Clínica Universidad de Navarra, Pamplona, Spain.
authors: Felipe
authors: F
authors: Prósper
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors: María
authors: M
authors: Díez-Campelo
authors: Servicio de Hematología, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain.
authors: Carmen
authors: C
authors: Regidor
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain; Red Nacional de Terapia Celular (TerCel), ISCIII, Spain.
authors: Eva
authors: E
authors: Villaron
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors: Lucía
authors: L
authors: López-Corral
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.
authors: Dolores
authors: D
authors: Caballero
authors: Servicio de Hematología, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain; Red Nacional de Terapia Celular (TerCel), ISCIII, Spain. Electronic address: concarol@usal.es.
authors: María-Consuelo Del
authors: MC
authors: Cañizo
authors: Servicio de Hematología, Instituto de biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. Electronic address: josea.perez.simon.sspa@juntadeandalucia.es.
authors: José Antonio
authors: JA
authors: Pérez-Simon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001792:Blood Platelets / Q000737:chemistry; D002452:Cell Count; D015925:Cryopreservation; 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; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D008875:Middle Aged; D011446:Prospective Studies; D013256:Steroids / Q000627:therapeutic use; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D013256:Steroids
keywords: Graft-versus-host disease (GVHD); Mesenchymal stromal cells (MSC)