title: Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia.
abstract: Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3 years was 51 % and not significantly influenced by number of HSCT (first HSCT 54 %, ≥second HSCT 44 %, p = 0.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p = 0.04 and 0.004). Treatment-related mortality was low at 14 %. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.
authors.affiliation: St. Anna Kinderspital and Children's Cancer Research Institute, Department of Paediatrics, Medical University of Vienna, Kinderspitalgasse 6, 1090, Vienna, Austria, heidrun.boztug@stanna.at.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Boztug
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Arjan
authors.initials: A
authors.lastname: Lankester
authors.forename: Mary
authors.initials: M
authors.lastname: Slatter
authors.forename: Roderick
authors.initials: R
authors.lastname: Skinner
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.forename: Evgenia
authors.initials: E
authors.lastname: Glogova
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007223:Infant; D008297:Male; D015999:Multivariate Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D012074:Remission Induction; D012189:Retrospective Studies; D013280:Stomatitis / Q000209:etiology; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
chemical_list: C018404:treosulfan; D002066:Busulfan