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 marrow transplant consortium study

Academic Article


  • 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 600mg/m2 and carmustine 300mg/m2 followed by thiotepa 600mg/m2 and carboplatin 1,200mg/m2. 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. © 2010 Wiley-Liss, Inc.
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    Author List

  • Gilman AL; Jacobsen C; Bunin N; Levine J; Goldman F; Bendel A; Joyce M; Anderson P; Rozans M; Wall DA
  • Start Page

  • 506
  • End Page

  • 513
  • Volume

  • 57
  • Issue

  • 3