More than half of the children and adolescents with malignant
brain tumors will relapse following initial
therapy. Irrespective of the therapeutic modalities the prognosis of patients with recurrent or metastatic
brain tumors is still poor. New strategies such as high dose
chemotherapy (HDCT) with autologous blood
stem cell transplantation (ABSCT) offer the possibility to improve the longterm prognosis of these patients. Following conventional
chemotherapy with
carboplatin/
etoposide and after achieving complete or partial remission (CR or PR) 10 patients aged from 3.2 to 25.5 years (median, 10.3 years) with refractory or recurrent malignant
brain tumors (
anaplastic astrocytoma/
glioblastoma, n = 2;
medulloblastoma/
PNET, n = 6;
ependymoma, n = 1; plexus
carcinoma, n = 1) received in a pilot study one course of HDCT with ABSCT. The consolidation regimen consisted of
thiotepa (400-600mg/m2/d, i.v. 6 h, d-9),
carboplatin and
etoposide (500mg/m2/d, CVI 24h, d-8 to d-5, respectively) and was followed by the retransfusion of autologous blood stem cells on day 0. Before starting HDCT 6 patients showed CR and 4 patients had PR or stable disease (SD). Following the HDCT 3 of the 4 patients with
residual tumor had CR or PR. 6 patients have remained in continuous CR or SD 8 to 41 months (median 17.2 months) after the HDCT. 2 patients relapsed 8.5 and 9.5 months after HDCT and died from progressive disease. Two patients died
therapy-related from systemic
aspergillosis and were not evaluable for response. Hematological recovery with an absolute neutrophile count of > 0.5 x 10(9)/l and a platelet count of > 30 x 10(9)/l was reached on days +11 (median; range, +9 to +14) and +16 (median; range, +6 to +47), respectively. The main nonhematological toxic effects were
infections, severe
mucositis, and
hyperbilirubinemia. Although the long-term efficacy of HDCT with ABSCT is still not evaluable and the toxicity of this regimen is high, a multicenter phase II trial seems to be justified in view of the poor prognosis of recurrent or refractory
brain tumors in children and adolescents.