Combination Chemotherapy and Radiation Therapy in Treating Younger Patients Who Are Undergoing an Autologous Stem Cell Transplant for Newly Diagnosed Gliomas

OBJECTIVES: Primary * Determine the safety and feasibility of a conditioning regimen comprising temozolomide, radiotherapy, and busulfan followed by an infusion of autologous stem cells genetically modified with the MGMT gene and temozolomide and O6-benzylguanine in younger patients with newly diagnosed high-grade gliomas. Secondary * Determine the tolerability of intrapatient dose escalation of temozolomide, in terms of transgene expression, in patients treated with this regimen. * Determine, preliminarily, the antitumor activity of this regimen in these patients. OUTLINE: This is a pilot study. * Surgery: Patients undergo biopsy or surgical debulking of the tumor. Two to six weeks later, patients proceed to stem cell mobilization and apheresis. * Autologous stem cell mobilization and apheresis: Patients receive filgrastim (G-CSF) subcutaneously or IV once daily for at least 4 days before apheresis and continuing until apheresis is complete. Patients undergo apheresis for up to 4 consecutive days until a target number of 5 X 10\^6 CD34-positive peripheral blood stem cells (PBSCs) are collected. Patients with insufficient numbers of PBSCs either undergo bone marrow harvest to collect a sufficient number of cells or are removed from the study. The cells are selected for CD34-positive cells which are cryopreserved for later use. Patients then proceed to chemoradiotherapy. * Chemoradiotherapy: Patients receive oral temozolomide once daily on days 1-42 and undergo radiotherapy once daily, 5 days a week, for 6 weeks. Four to eight weeks later, patients proceed to the low-intensity, nonmyeloablative conditioning regimen. * Autologous PBSC or bone marrow transduction: Peripheral blood or bone marrow CD34-positive stem cells are transduced with the MGMT gene on day -4. * Low-intensity, nonmyeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -3 and -2. Patients then proceed to autologous PBSC or bone marrow infusion. * Autologous PBSC or bone marrow infusion: Patients undergo autologous stem cell infusion using transduced PBSCs or bone marrow on day 0. Three to six weeks later, patients proceed to chemotherapy. * Chemotherapy: Patients receive O6-benzylguanine IV over 1 hour followed by oral temozolomide once daily on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing unacceptable toxicity due to O6-benzylguanine may receive temozolomide alone. Patients not experiencing dose-limiting toxicity and who have at least 5% transduced neutrophils by peripheral blood analysis after course 1 receive escalating doses (intrapatient) of temozolomide during courses 2-6. Some patients undergo second-look surgery after the first course of chemotherapy. After completion of study therapy, patients are followed monthly for 3 months, every 3 months for 3 years, every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 1-2 years.