title: Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases.
abstract: An increasing number of children with non-malignant diseases can be cured by allogeneic haematopoietic stem cell transplantation (HSCT). Treosulfan (L-treitol-1,4-bis-methanesulfonate) is being used more frequently for conditioning, owing to its' lower toxicity profile compared with conventional myeloablative regimens. A retrospective analysis was performed of children registered in the EBMT database, who received treosulfan before HSCT between January 2005 and 2010, to identify possible dose-related toxicity and determine the incidence of engraftment, treatment-related mortality and overall survival (OS). Results from 316 transplants from 11 different countries are presented. Ninety-five (30%) were under 1 year of age at the time of transplant. OS was 83% and event-free survival was 76%; 3-year OS and event-free survival of infants below 1 year were 79% and 73%, respectively. No association was found with age at transplant, dose of treosulfan given, other agents used in combination with treosulfan, donor type, stem cell source, or second or subsequent transplant. In this report of the largest number of children to date receiving treosulfan for non-malignant diseases, treosulfan is shown to be a safe and effective agent even for those under 1 year of age at the time of transplant. Further prospective studies are needed using precisely defined protocols with pharmacokinetic monitoring and detailed chimerism analysis. In addition, long-term studies will be vital to determine long-term effects, for example, on fertility in comparison with other regimens.
authors.affiliation: Paediatric Immunology Department, Paediatric HSCT, Great North Children's Hospital, Newcastle upon Tyne, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: Department of Paediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Boztug
authors.affiliation: Department of Paediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Pötschger
authors.affiliation: Department of Paediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: K-W
authors.initials: KW
authors.lastname: Sykora
authors.affiliation: Department of Paediatrics, Leiden University Medical Center, RC Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Lankester
authors.affiliation: Sackler Faculty of Medicine, Paediatric Hematology Oncology Schneider Children's Medical Center of Israel, Tel Aviv University, Tel Aviv, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Yaniv
authors.affiliation: Department of Paediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University Motol Prague, Motol Prague, Czech Republic.
authors.forename: P
authors.initials: P
authors.lastname: Sedlacek
authors.affiliation: Department of Paediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Glogova
authors.affiliation: Paediatric HSCT, Great Ormond Street Hospital for Children National Health Service Trust, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Veys
authors.affiliation: Paediatric Immunology Department, Paediatric HSCT, Great North Children's Hospital, Newcastle upon Tyne, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Gennery
authors.affiliation: Department of Paediatrics, St. Anna Kinderspital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
authors.forename: C
authors.identifier: http://orcid.org/0000-0003-0369-8515
authors.initials: C
authors.lastname: Peters
mesh_terms: D000293:Adolescent; D000367:Age Factors; D064591:Allografts; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: C018404:treosulfan; D002066:Busulfan