ETOPOSIDE CONTAINING REGIMENS WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN CHILDREN WITH MALIGNANT BRAIN-TUMORS

Despite improvements in neurosurgical and neuroradiotherapeutic techni ques, children with malignant brain tumors have a dismal prognosis. In an attempt to improve the efficacy of cytotoxic therapy, dose intensi fication of effective chemotherapeutic agents followed by autologous b one marrow transplantation (BMT) has been tried. Between May 1991 and August 1996, high-dose chemotherapy and autologous BMT were administer ed to 11 children with malignant brain tumors: 10 had recurrent (n=8) or progressive (n=2) disease, and I was treated before progression. Th e histological diagnoses were medulloblastoma (3), glioblastoma multif orme (2), supratentorial PNET (2), ependymoma (2), anaplastic astrocyt oma (1), and anaplastic oligodendroglioma (I). In 6 of the 11 patients measurable disease was present at the time of BMT. The preparative re gimen included BCNU 600 mg/m(2) and VP16 1500 mg/m(2) in 5 cases, and thiotepa 900 mg/m(2) and VP16 1500 mg/m in 6 cases. The median times t o achieve a neutrophil count over 0.5x10(9)/l and a platelet count ove r 50x10(9)/l were 14 and 28 days, respectively. The overall incidence of severe toxicity (grade III-IV) was 18% and consisted of oropharynge al mucositis and diarrhea. Among the 6 patients with measurable diseas e at the time of BMT there were 2 with stable disease, whereas 3 patie nts had tumor progression: all these patients died of tumor recurrence 2-10 months after BMT. Five patients in whom there was no evidence of disease at the time of BMT are alive and free of progression with a m edian follow-up of 20 months (range 3-67). These preliminary results s how that high-dose chemotherapy and BMT may be effective in children w ith malignant brain tumors. Etoposide-containing regimens seem to have significant activity in this setting, and the toxicity was manageable . The most important variable prognostic for progression-free survival is the disease status at the time of transplantation.