High-dose busulfan-thiotepa with autologous stem cell transplantation followed by posterior fossa irradiation in young children with classical or incompletely resected medulloblastoma

Pediatr Blood Cancer. 2014 May;61(5):907-12. doi: 10.1002/pbc.24954. Epub 2014 Jan 28.

Abstract

Background: The aim of the study is to evaluate the outcome of young children with high risk localized medulloblastomas (newly diagnosed classical or incompletely resected) treated by high-dose busulfan-thiotepa with autologous stem cell rescue (ASCT) followed by focal radiation therapy (RT).

Procedure: Between September 1994 and January 2010, 19 children younger than 5 years old at diagnosis fulfilling the above inclusion criteria were treated at the Institute Gustave Roussy. After conventional chemotherapy, they received busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by ASCT. Focal RT was delivered at least 70 days after ASCT.

Results: The median follow-up was 40.5 months (range, 14.5-191.2 months). The 3-year event-free survival (EFS) and OS were 68% (95% CI 45-84%) and 84% (95% CI 61-94%), respectively. Acute toxicity consisted mainly in hepatic veno-occlusive disease (6/19 patients) and bone marrow aplasia (all patients). No toxic death occurred. The Full Scale Intellectual Quotient tended to decrease over time at a mean rate of 0.9 point per year from the date of diagnosis.

Conclusions: This intensive treatment resulted in a high overall survival rate in young children with newly diagnosed non-metastatic classic or incompletely resected MB. In spite of a high incidence of hepatic veno-occlusive disease (32%), the acute toxicity was manageable. Delayed neuropsychological side effects remain main concerns. These results should to be confirmed in a larger cohort.

Keywords: childhood; high-dose chemotherapy; medulloblastoma; stem-cell transplantation.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Cerebellar Neoplasms / surgery
  • Cerebellar Neoplasms / therapy*
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infratentorial Neoplasms / surgery
  • Infratentorial Neoplasms / therapy*
  • Male
  • Medulloblastoma / surgery
  • Medulloblastoma / therapy*
  • Neuropsychological Tests
  • Prognosis
  • Retrospective Studies
  • Stem Cell Transplantation*
  • Thiotepa / administration & dosage
  • Transplantation, Autologous

Substances

  • Thiotepa
  • Busulfan