title: High-dose busulfan and thiotepa followed by autologous stem cell transplantation (ASCT) in previously irradiated medulloblastoma patients: high toxicity and lack of efficacy.
abstract: We previously demonstrated that Busulfan-Thiotepa (Bu-Thio) and ASCT effectively treated patients with locally relapsed medulloblastoma after surgery and conventional chemotherapy. We thus evaluated the administration of Bu-Thio in patients relapsing after conventional CNS irradiation. Patients were scheduled to receive Busulfan (600 mg/m(2)) and Thiotepa (900 mg/m(2)) and ASCT. Resection of residual tumour and additional irradiation were performed if necessary and feasible after Bu-Thio. Toxicity was compared to that observed in 35 patients treated without previous CNS irradiation. From 5/88 to 3/02, 15 patients were treated according to this strategy. Toxicity was significantly higher than that observed in unirradiated patients: thrombocytopenia <50,000/mm(3) lasting 56 days (13-732) (P=0.02) and 30 days (4-124), respectively, HVOD (10/15 and 12/35 patients, respectively) (P=0.06), neurological toxicity (8/15 vs 3/35 patients) (P=0.01). Tumour response was assessable in seven patients and consisted in two CR, three PR and two NR. Currently, two of 15 patients are alive with no evidence of disease. In conclusion, the toxicity of Bu-Thio was significantly more severe in previously irradiated patients. In spite of a high response rate, this strategy failed to improve the prognosis of previously irradiated patients with a relapse from a medulloblastoma.
authors.affiliation: Pediatrics Department, Institut Gustave Roussy, Villejuif, France. valteau@igr.fr
authors.forename: D
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: B
authors.initials: B
authors.lastname: Fillipini
authors.forename: E
authors.initials: E
authors.lastname: Benhamou
authors.forename: J
authors.initials: J
authors.lastname: Grill
authors.forename: C
authors.initials: C
authors.lastname: Kalifa
authors.forename: D
authors.initials: D
authors.lastname: Couanet
authors.forename: J L
authors.initials: JL
authors.lastname: Habrand
authors.forename: O
authors.initials: O
authors.lastname: Hartmann
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage* / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D020258:Neurotoxicity Syndromes / Q000209:etiology; D012074:Remission Induction / Q000379:methods; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage* / Q000633:toxicity; D013921:Thrombocytopenia / Q000209:etiology; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D013852:Thiotepa; D002066:Busulfan