High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

J Neurooncol. 2005 Jan;71(1):33-8. doi: 10.1007/s11060-004-4527-4.

Abstract

Current treatment for high risk and recurrent medulloblastoma (MB) and supratentorial primitive neuroectodermal tumors (stPNET) has a very poor prognosis in children. High dose chemotherapy (HDCT) and autologous stem cell rescue have improved survival rates. We present 19 patients (thirteen classified in the high risk group and six patients with recurrent disease) that received HDCT and autologous stem cell rescue. In the high risk group [Med Pediatr Oncol 38 (2002) 83], all patients underwent neurosurgical debulking. Standard chemotherapy was prescribed in 10 patients. Radiotherapy was given to 4 patients (all older than 4 years old). In the recurrence disease group [Childs Nerv Syst 15 (1999) 498], five patients underwent surgery. Radiotherapy was given to those who were not previously irradiated. The HDCT in twelve patients consisted of busulfan 4 mg/kg/day, orally over 4 days in 6-hourly divided doses and melphalan at a dose of 140 mg/m2/day by intravenous infusion over 5 min on day -1. Three patients additionally received thiotepa 250 mg/m2/day intravenously over 2 days and four patients additionally received topotecan 2 mg/m2/day over 5 days by intravenous infusion over 30 min. The other seven patients received busulfan and thiotepa at the same doses.Patient's stem cells were mobilized with granulocyte colony-stimulating factor at a dose of 12 microg/kg twice daily subcutaneously for four consecutive days. Cryopreserved peripheral blood progenitor cells were re-infused 48 h after completion of chemotherapy. With a median follow-up of 34 months (range 5-93) eight complete responses and one partial response were observed. Three patients died of treatment-related toxicities (15%). The 2 year event-free survival was 37.67+/-14% in all patients and 57+/-15% for the high risk group. Therefore we conclude that HDCT may improve survival rates in patients with high risk/recurrent MB and stPNET despite treatment toxicity.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Busulfan / administration & dosage
  • Cerebellar Neoplasms / mortality
  • Cerebellar Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Medulloblastoma / mortality
  • Medulloblastoma / therapy*
  • Melphalan / administration & dosage
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy*
  • Neuroectodermal Tumors, Primitive / mortality
  • Neuroectodermal Tumors, Primitive / therapy*
  • Peripheral Blood Stem Cell Transplantation*
  • Radiotherapy, Adjuvant
  • Supratentorial Neoplasms / mortality
  • Supratentorial Neoplasms / therapy*
  • Thiotepa / administration & dosage
  • Topotecan / administration & dosage
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Topotecan
  • Thiotepa
  • Busulfan
  • Melphalan