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

Pediatr Blood Cancer. 2011 Sep;57(3):506-13. doi: 10.1002/pbc.22899. Epub 2010 Dec 1.


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.

Procedures: 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.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Brain Neoplasms / complications
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy*
  • Carboplatin
  • Carmustine
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Maximum Tolerated Dose
  • Peripheral Blood Stem Cell Transplantation / methods*
  • Peripheral Blood Stem Cell Transplantation / mortality
  • Survival Analysis
  • Thiotepa
  • Transplantation, Autologous


  • Thiotepa
  • Carboplatin
  • Carmustine