title: European Society for Blood and Marrow Transplantation Analysis of Treosulfan Conditioning Before Hematopoietic Stem Cell Transplantation in Children and Adolescents With Hematological Malignancies.
abstract: BACKGROUND
  Standard myeloablative conditioning regimens for children with hematological malignancies undergoing allogeneic HSCT are based mainly on total body irradiation or busulfan. Their serious short- and long-term side effects warranted the exploration of less toxic alternatives. Treosulfan is increasingly used for adults and children before HSCT due to its potent immunosuppressive and cytotoxic effects combined with low organ toxicity.
  
  
  METHODS
  To further investigate the role of treosulfan conditioning in children, the EBMT Pediatric diseases working party performed a retrospective analysis of 193 children with hematological malignancies (ALL n = 71, AML n = 47, MDS/MPS n = 40, other leukemia/lymphoma n = 25) undergoing allogeneic HSCT following treosulfan between January 2005 and July 2010.
  
  
  RESULTS
  Early regimen-related toxicity was low and mainly gastrointestinal. Veno-occlusive disease and neurological toxicity were rare. There was no association of toxicity with type of disease or treosulfan dose. High-grade early toxicity was not higher in infants or patients undergoing second or later transplantation. Treatment related mortality was low at 14%. Three-year event-free survival was 45 ± 4% and not significantly influenced by number of transplants, however it appeared to be significantly better for infants (P = 0.022). When compared to treosulfan plus fludarabine, the combination of treosulfan, fludarabine and an alkylator (either thiotepa or melphalan) resulted in significantly better overall survival (OS, P = 0.048) and a trend toward better EFS.
  
  
  CONCLUSIONS
  Treosulfan based conditioning is a safe and effective approach for children with hematological malignancies, including and importantly for infants and those patients undergoing second or later transplantation.
authors.affiliation: St. Anna Kinderspital and Childrens Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Boztug
authors.affiliation: Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Sykora
authors.affiliation: Children's HSCT Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary
authors.initials: M
authors.lastname: Slatter
authors.affiliation: Pediatric Hematology/Oncology, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Lankester
authors.affiliation: Children's HSCT Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.affiliation: Children's HSCT Unit, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.
authors.forename: Roderick
authors.initials: R
authors.lastname: Skinner
authors.affiliation: Department of Pediatric Hematology, Oncology, and Hematopoietic Stem Cell Transplantation, University of Medical Sciences, Poznań, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Wachowiak
authors.affiliation: St. Anna Kinderspital and Childrens Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Glogova
authors.affiliation: St. Anna Kinderspital and Childrens Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Pötschger
authors.affiliation: St. Anna Kinderspital and Childrens Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001803:Blood Transfusion; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000628:therapy*; D008297:Male; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012955:Societies, Medical; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: children; hematological malignancy; stem cell transplantation; toxicity; treosulfan