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

Andrew L. Gilman, Chad Jacobsen, Nancy Bunin, John Levine, Fred Goldman, Anne Bendel, Michael Joyce, Peter Anderson, Marta Rozans, Donna A. Wall, Tobey J. Macdonald, Steve Simon, Richard P. Kadota

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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. 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.

Original languageEnglish
Pages (from-to)506-513
Number of pages8
JournalPediatric Blood and Cancer
Volume57
Issue number3
DOIs
StatePublished - Sep 2011
Externally publishedYes

Keywords

  • Brain tumors
  • Myeloablative therapy
  • Phase I clinical trials
  • Stem cell transplantation

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