title: Phase I study of tandem high-dose chemotherapy with autologous peripheral blood stem cell rescue for children with recurrent brain tumors: a Pediatric Blood and MarrowTransplant Consortium study.
abstract: BACKGROUND
  High-dose chemotherapy with autologous stem cell rescue (HDC/SCR) has produced responses and prolonged survival for some children with recurrent brain tumors, but is associated with considerable morbidity and mortality. A Phase I trial of two cycles of HDC/SCR for recurrent brain tumors in children was performed to determine the maximum tolerated doses for a novel regimen.
  
  
  METHODS
  Two cycles of HDC/SCR were given. Cycle 1 included thiotepa and carmustine given on days -5, -4, and -3. Four to six weeks later, patients received cycle 2 which included thiotepa and carboplatin given on days -5, -4, and -3. Autologous peripheral blood stem cells (PBSC) were infused on day 0 of each cycle.
  
  
  RESULTS
  Thirty-two patients were treated and 25 patients received both cycles of HDC/SCR. Common toxicities included mucositis, emesis, diarrhea, anorexia, and pancytopenia. Eight of 32 (25%) assessable children died from regimen-related toxicity. Pulmonary failure occurred in seven patients. Seven patients had grade 3-4 neurotoxicity. The 3-year event-free survival (EFS) was 25%.
  
  
  CONCLUSIONS
  We determined the maximum tolerated regimen to be thiotepa 600 mg/m(2) and carmustine 300 mg/m(2) followed by thiotepa 600 mg/m(2) and carboplatin 1,200 mg/m(2) . Pulmonary toxicity was considerable. The toxic death rate was similar to other trials of HDC/SCR for children with recurrent brain tumors performed during the same time period. The regimen resulted in prolonged time to progression for a significant number of patients and long-term survival for some patients with recurrent medulloblastoma and rhabdoid tumor.
authors: Levine Children's Hospital, Charlotte, NC, USA. andrew.gilman@carolinashealthcare.org
authors: Andrew L
authors: AL
authors: Gilman
authors: Chad
authors: C
authors: Jacobsen
authors: Nancy
authors: N
authors: Bunin
authors: John
authors: J
authors: Levine
authors: Fred
authors: F
authors: Goldman
authors: Anne
authors: A
authors: Bendel
authors: Michael
authors: M
authors: Joyce
authors: Peter
authors: P
authors: Anderson
authors: Marta
authors: M
authors: Rozans
authors: Donna A
authors: DA
authors: Wall
authors: Tobey J
authors: TJ
authors: Macdonald
authors: Steve
authors: S
authors: Simon
authors: Richard P
authors: RP
authors: Kadota
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001932:Brain Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016190:Carboplatin; D002330:Carmustine; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D020714:Maximum Tolerated Dose; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D016019:Survival Analysis; D013852:Thiotepa; D014182:Transplantation, Autologous
chemical_list: D013852:Thiotepa; D016190:Carboplatin; D002330:Carmustine