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ANZCCSG BabyBrain99 is a trial of intensive systemic chemotherapy with dual stem cell supported treatment, second look surgery and involved field radiation for children less than four years of age with malignant central nervous system tumours.Following primary resection, treatment included two courses of cisplatin and oral etoposide, a third course of mobilising chemotherapy (vincristine, etoposide, cyclophosphamide) with stem cell harvest, followed by intensive stem cell supported chemotherapy with high dose cyclophosphamide, etoposide and vincristine. Children were evaluated for second resection before proceeding to a second stem cell supported consolidation therapy consisting of melphalan and carboplatin. Patients then received involved field radiation therapy.Thirty three children with a range of diagnoses were enrolled. Nine percent of children had metastatic disease at diagnosis. Eighteen children completed treatment including irradiation. At the end of induction the event free survival was 70% (54–86). Forty eight percent of children had a complete response, 18% had stable disease and 3% had a partial response. Five year overall survival was 40% (22–56) and event free survival was 33% (17–50). Children in whom a complete resection were achieved had a significantly superior outcome compared to those children without a complete resection, 5 year EFS 60% (45–75), as compared to 22% (13–30), P-value <0.05.BabyBrain99 confirms that intensive stem cell supported chemotherapy can be safely administered to infants with CNS tumours however overall prognosis remains poor. Importantly, the study reinforces a complete surgical resection as an important favourable prognostic indicator. Pediatr Blood Cancer 2011;56:1055–1061. © 2011 Wiley-Liss, Inc.