High-dose chemotherapy with autologous stem cell rescue in children under 5 years of age with central nervous system embryonal tumors: results from a prospective cohort in an upper-middle-income country

PURPOSE: High-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) has been employed to mitigate the long-term side effects of radiotherapy and improve survival outcomes in infants with embryonal central nervous system (CNS) tumors. METHODS: This prospective study, supported by federal funding from the National Oncological Care Support Program, included children younger than 5 years of age with newly diagnosed CNS embryonal tumors treated with surgery and HDCT/ASCR. RESULTS: Between 2016 and 2019, 36 patients were included: 22 with medulloblastoma (MB) and 14 with other CNS embryonal tumors. In the MB cohort, the mean age was 2.5 years, 13 were male. Gross total resection (GTR) was achieved in 18 patients; 15 had non-metastatic disease (M0). Among non-MB patients, the mean age was 2.7 years, 11 were female. Nine patients had GTR; 12 had M0. According to the MB molecular subgroup, the 2- and 5-year event-free survival (EFS) rates for the SHH subgroup were 76.9%, and overall survival (OS) was 92.3%. For the non-WNT/non-SHH subgroup, the 2- and 5-year EFS rates were 33.3% and 22.2%, and OS, 66.7% and 55.6%, respectively. Two SHH and five non-WNT/non-SHH patients were successfully salvaged with craniospinal irradiation after a mean of 12 months (range, 7-36 months). Among non-MB patients, the 2- and 5-year EFS and OS were 28.6/19.0% and 42.9/32.1%, respectively. All patients developed grade 3-4 mucositis/typhlitis and febrile neutropenia and 13.9% invasive fungal infections during HDCT. CONCLUSION: HDCT/ASCR is feasible in a middle-income country setting and provides favorable outcomes in SHH medulloblastoma. However, prognosis remains poor for non-SHH MB and other embryonal tumors, highlighting the need for novel molecularly guided therapies.