High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors.
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.
Pérez-Martínez
Antonio
A
Department of Pediatric Hematology and Oncology, Hospital Niño Jesús, Universidad Autónoma de Madrid, Spain.
Lassaletta
Alvaro
A
González-Vicent
Marta
M
Sevilla
Julián
J
Díaz
Miguel Angel
MA
Madero
Luis
L
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
D000970:Antineoplastic Agents; D019772:Topotecan; D013852:Thiotepa; D002066:Busulfan; D008558:Melphalan
Med Pediatr Oncol. 1998 Dec;31(6):506-11
9835903
J Clin Oncol. 1999 Mar;17(3):832-45
10071274
Bone Marrow Transplant. 2002 Oct;30(7):417-20
12368952
Childs Nerv Syst. 1999 Oct;15(10):498-505
10550581
Crit Rev Oncol Hematol. 2002 Feb;41(2):197-204
11856595
Bone Marrow Transplant. 1999 Dec;24(11):1157-9
10642802
J Neurooncol. 1998 Jun-Jul;38(2-3):187-92
9696370
J Clin Oncol. 1998 Jan;16(1):210-21
9440745
J Clin Oncol. 1997 May;15(5):1814-23
9164190
Med Pediatr Oncol. 2002 Feb;38(2):83-90
11813171
Bone Marrow Transplant. 1992 Apr;9(4):227-33
1534708
J Neurosurg. 1982 Oct;57(4):446-51
7108593
J Clin Oncol. 1998 May;16(5):1723-8
9586884
J Clin Oncol. 1998 Jul;16(7):2486-93
9667268
Cancer. 1987 Oct 1;60(7):1651-6
3621134
Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):13-47
10758303
J Clin Oncol. 1998 Jan;16(1):222-8
9440746
Bone Marrow Transplant. 2002 Sep;30(6):355-8
12235519
Cancer. 1985 Oct 1;56(7 Suppl):1807-9
4027916