title: High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors.
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.
authors.affiliation: Department of Pediatric Hematology and Oncology, Hospital Niño Jesús, Universidad Autónoma de Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pérez-Martínez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Lassaletta
authors.forename: Marta
authors.initials: M
authors.lastname: González-Vicent
authors.forename: Julián
authors.initials: J
authors.lastname: Sevilla
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Díaz
authors.forename: Luis
authors.initials: L
authors.lastname: Madero
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000628:therapy*; D008558:Melphalan / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy*; D018242:Neuroectodermal Tumors, Primitive / Q000401:mortality / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D018714:Radiotherapy, Adjuvant; D015173:Supratentorial Neoplasms / Q000401:mortality / Q000628:therapy*; D013852:Thiotepa / Q000008:administration & dosage; D019772:Topotecan / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019772:Topotecan; D013852:Thiotepa; D002066:Busulfan; D008558:Melphalan
references.citation: Med Pediatr Oncol. 1998 Dec;31(6):506-11
references.pmid: 9835903
references.citation: J Clin Oncol. 1999 Mar;17(3):832-45
references.pmid: 10071274
references.citation: Bone Marrow Transplant. 2002 Oct;30(7):417-20
references.pmid: 12368952
references.citation: Childs Nerv Syst. 1999 Oct;15(10):498-505
references.pmid: 10550581
references.citation: Crit Rev Oncol Hematol. 2002 Feb;41(2):197-204
references.pmid: 11856595
references.citation: Bone Marrow Transplant. 1999 Dec;24(11):1157-9
references.pmid: 10642802
references.citation: J Neurooncol. 1998 Jun-Jul;38(2-3):187-92
references.pmid: 9696370
references.citation: J Clin Oncol. 1998 Jan;16(1):210-21
references.pmid: 9440745
references.citation: J Clin Oncol. 1997 May;15(5):1814-23
references.pmid: 9164190
references.citation: Med Pediatr Oncol. 2002 Feb;38(2):83-90
references.pmid: 11813171
references.citation: Bone Marrow Transplant. 1992 Apr;9(4):227-33
references.pmid: 1534708
references.citation: J Neurosurg. 1982 Oct;57(4):446-51
references.pmid: 7108593
references.citation: J Clin Oncol. 1998 May;16(5):1723-8
references.pmid: 9586884
references.citation: J Clin Oncol. 1998 Jul;16(7):2486-93
references.pmid: 9667268
references.citation: Cancer. 1987 Oct 1;60(7):1651-6
references.pmid: 3621134
references.citation: Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):13-47
references.pmid: 10758303
references.citation: J Clin Oncol. 1998 Jan;16(1):222-8
references.pmid: 9440746
references.citation: Bone Marrow Transplant. 2002 Sep;30(6):355-8
references.pmid: 12235519
references.citation: Cancer. 1985 Oct 1;56(7 Suppl):1807-9
references.pmid: 4027916