title: Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the 'Head Start' trials, 1991-2009.
abstract: Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (<6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.
authors.affiliation: Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Altshuler
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Haley
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dhall
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Vasquez
authors.affiliation: Stephen D. Hassenfeld Children's Center for Cancer and Blood Disorders, New York University Langone Medical Center, New York, NY, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Gardner
authors.affiliation: Division of Hematology, Oncology and BMT, Nationwide Children's Hospital and the Ohio State University, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stanek
authors.affiliation: Neuro-oncology Program, Division of Hematology, Oncology and BMT, Nationwide Children's Hospital and the Ohio State University, Columbus, OH, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Finlay
mesh_terms: D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002986:Clinical Trials as Topic / Q000592:standards*; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality / Q000639:trends; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D009017:Morbidity / Q000639:trends; D009026:Mortality / Q000639:trends; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D014182:Transplantation, Autologous
chemical_list: D019653:Myeloablative Agonists