title: 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.
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.
authors.affiliation: Paediatric Department, Institut Gustave Roussy, Villejuif, France.
authors.forename: O
authors.initials: O
authors.lastname: Hartmann
authors.forename: D
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: E
authors.initials: E
authors.lastname: Benhamou
authors.forename: G
authors.initials: G
authors.lastname: Vassal
authors.forename: H
authors.initials: H
authors.lastname: Rubie
authors.forename: F
authors.initials: F
authors.lastname: Beaujean
authors.forename: J
authors.initials: J
authors.lastname: Lemerle
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: C048341:mafosfamide; D003520:Cyclophosphamide; D002066:Busulfan; D008558:Melphalan