title: High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas.
abstract: OBJECTIVE
  Evaluation of high-dose chemotherapy with autologous bone marrow rescue (ABMR) in pediatric malignant gliomas.
  
  
  METHODS
  Newly diagnosed (n = 11) and recurrent (n = 2) malignant glioma patients received high-dose chemotherapy within 4 weeks of surgery; three had near total and 10 had subtotal resection/biopsy. High-dose thiotepa (300 mg/m2) and cyclophosphamide (2 g/m2) daily for 3 days were followed by ABMR; response was evaluated at day 30. At day 60, patients with at least stable disease received hyperfractionated (n = 9) or conventional external-beam radiotherapy (n = 2) preceded by local radioactive iodine 125 implantation (n = 2) or radiosurgery (n = 1).
  
  
  RESULTS
  Grade III and IV toxicities after ABMR consisted of mucositis (n = 12), cardiomyopathy (n = 1), acute abdomen (n = 1), pneumonitis (n = 2), and infection (n = 2). One complete and three partial responses were observed; the objective response rate was 31% (95% confidence interval, 9% to 61%). Seven had stable disease, one had disease progression, and one died of toxicity before response evaluation. The median overall and progression-free survival durations after combined modality therapy were 14 months (range, 4 to 30+) and 9 months (range, 0 to 30+), respectively. One patient remains progression-free at 30+ months. Radionecrosis and white matter changes occurred in three patients: one after hyperfractionated irradiation, and two after 125I implants.
  
  
  CONCLUSIONS
  For patients with bulky residual disease after surgery, survival with this aggressive chemotherapy and radiation regimen is not better than that reported for conventional treatment regimens.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38101.
authors.forename: R L
authors.initials: RL
authors.lastname: Heideman
authors.forename: E C
authors.initials: EC
authors.lastname: Douglass
authors.forename: R A
authors.initials: RA
authors.lastname: Krance
authors.forename: J
authors.initials: J
authors.lastname: Fontanesi
authors.forename: J A
authors.initials: JA
authors.lastname: Langston
authors.forename: R A
authors.initials: RA
authors.lastname: Sanford
authors.forename: E H
authors.initials: EH
authors.lastname: Kovnar
authors.forename: J
authors.initials: J
authors.lastname: Ochs
authors.forename: J
authors.initials: J
authors.lastname: Kuttesch
authors.forename: J J
authors.initials: JJ
authors.lastname: Jenkins
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001918:Brachytherapy; D001932:Brain Neoplasms / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000628:therapy*; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011878:Radiotherapy / Q000379:methods; D013852:Thiotepa / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D003520:Cyclophosphamide; D013852:Thiotepa