title: Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan.
abstract: Hepatic veno-occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5-40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen-matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan-based conditioning, methotraexate + ciclosporine). All patients received a busulphan-based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day -9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high-risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low-weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.
authors.affiliation: Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cappelli
authors.forename: Robert
authors.initials: R
authors.lastname: Chiesa
authors.forename: Costanza
authors.initials: C
authors.lastname: Evangelio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Biffi
authors.forename: Tito
authors.initials: T
authors.lastname: Roccia
authors.forename: Ilaria
authors.initials: I
authors.lastname: Frugnoli
authors.forename: Erika
authors.initials: E
authors.lastname: Biral
authors.forename: Anna
authors.initials: A
authors.lastname: Noè
authors.forename: Marco
authors.initials: M
authors.lastname: Fossati
authors.forename: Valentina
authors.initials: V
authors.lastname: Finizio
authors.forename: Roberto
authors.initials: R
authors.lastname: Miniero
authors.forename: Sara
authors.initials: S
authors.lastname: Napolitano
authors.forename: Francesca
authors.initials: F
authors.lastname: Ferrua
authors.forename: Clara
authors.initials: C
authors.lastname: Soliman
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Maria G
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Sarah
authors.initials: S
authors.lastname: Marktel
mesh_terms: D000293:Adolescent; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004341:Drug Evaluation; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006504:Hepatic Veno-Occlusive Disease / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use*; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D017086:beta-Thalassemia / Q000628:therapy*
chemical_list: D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D002066:Busulfan