The study is being performed within the Pediatric Brain Tumor Consortium, a group of institutions nationwide, that specialize in treating children with brain tumors. Two groups of pediatric CNS tumor patients are eligible-those with diffuse intrinsic pontine glioma which is a deadly disease which primarily strikes children 5-10 years of age and has a median survival of &lt;1 year, and recurrent high-grade gliomas which also has a similarly poor prognosis. Determination that activity of temozolomide was not improved when administered with the MGMT modulating agent, O6BG, in children with recurrent or progressive gliomas. Forty-three patients were enrolled on this Ph II study performed within the Pediatric Brain Tumor Consortium (PBTC), with 41 assessable for response. One sustained partial response was observed in the high grade glioma cohort, and no sustained objective responses were observed in the brainstem glioma cohort. We concluded that the combination of O6BG and TMZ did not improve efficacy of TMZ over TMZ alone in pediatric patients with recurrent or progressive HGG and BSG. An important aspect of this study was central pathology review. Five patients initially diagnosed as HGG who had an objective response or long-term stable disease were included and upon central review, the diagnoses for these cases included ganglioglioma (n=1), anaplastic astrocytoma (n=1), and one case classified differently by each neuropathologist as pilocytic astrocytoma, ganglioglioma, or astrocytic glioma. The fact that at least 2 of the 5 patients with objective response or long term stable disease did not have HGG demonstrates the importance of central review.