Stage IV neuroblastoma in patients over 1 year of age at diagnosis: consolidation of poor responders with combined busulfan, cyclophosphamide and melphalan followed by in vitro mafosfamide-purged autologous bone marrow transplantation

Eur J Cancer. 1997 Oct;33(12):2126-9. doi: 10.1016/s0959-8049(97)00227-x.

Abstract

In an attempt to improve the poor prognosis of poor responders with stage IV neuroblastoma, a new combined high-dose chemotherapy conditioning regimen was tested. Event-free and overall survival, as well as the incidence of complications, were analysed. Twenty-five children aged 12-146 months at diagnosis entered this study. All were in complete remission (CR) at the time of high-dose chemotherapy. Two or three different protocols had been necessary for them to achieve a CR. High-dose chemotherapy consisted of a combination of busulfan (600 mg/m2), cyclophosphamide (4400 mg/m2) and melphalan (140 mg/m2). It was followed by autologous bone marrow transplantation (ABMT). The bone marrow graft was purged in vitro with mafosfamide. The probability of event-free survival (EFS) at 5 years post-ABMT was 34%, compared to < 8% in a historical series. Toxicity was severe but manageable and 2 complication-related deaths were observed. Veno-occlusive disease was the most frequent extrahaematopoietic complication encountered, but its outcome was always favourable. By using a very intensive conditioning regimen consisting of a combination of three alkylating agents, the EFS of poor responders with metastatic neuroblastoma was improved and similar to that of good responders. When compared with a previously published similar series of patients, the improvement in survival appears probably related to intensification of the conditioning regimen.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Purging*
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Melphalan / administration & dosage
  • Melphalan / adverse effects
  • Neoplasm Metastasis
  • Neuroblastoma / pathology
  • Neuroblastoma / therapy*
  • Remission Induction
  • Treatment Outcome

Substances

  • mafosfamide
  • Cyclophosphamide
  • Busulfan
  • Melphalan