High-dose chemotherapy with autologous stem-cell rescue in patients with recurrent and high-risk pediatric brain tumors.

PURPOSE: We treated 49 patients with recurrent or poor-prognosis CNS malignancies with high-dose chemotherapy regimens followed by autologous marrow rescue with or without peripheral-blood stem-cell augmentation to determine the toxicity of and event-free survival after these regimens. PATIENTS AND METHODS: Nineteen patients had medulloblastomas, 12 had glial tumors, seven had pineoblastomas, five had ependymomas, three had primitive neuroectodermal tumors, two had germ cell tumors, and one had fibrosarcoma. Thirty-seven received chemotherapy with cyclophosphamide 1.5 g/m2 daily x 4 and melphalan 25 to 60 mg/m2 daily x 3. Nine received busulfan 37.5 mg/m2 every 6 hours x 16 and melphalan 180 mg/m2 (n = 7) or 140 mg/m2 (n = 2). Three received carboplatin 700 mg/m2/d on days -7, -5, and -3 and etoposide 500 mg/m2/d on days -6, -4, and -2. All patients received standard supportive care.
RESULTS: Eighteen of 49 patients survive event-free 22+ to 55+ months (median, 33+) after transplantation, including nine of 16 treated before recurrence and nine of 33 treated after recurrence. There was one transplant-related death from pulmonary aspergillosis. Of five patients assessable for disease response, one had a partial remission (2 months), one has had stable disease (55+ months), and three showed progression 2, 5, and 8 months after transplantation.
CONCLUSION: The toxicity of these regimens was tolerable. Certain patients with high-risk CNS malignancies may benefit from such a treatment approach. Subsequent trials should attempt to determine which patients are most likely to benefit from high-dose chemotherapy with autologous stem-cell rescue.