HIGH-DOSE MELPHALAN AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS BONE-MARROW RESCUE FOR RECURRENT PROGRESSIVE MALIGNANT BRAIN-TUMORS IN CHILDREN - A PILOT PEDIATRIC-ONCOLOGY-GROUP STUDY

Purpose: To determine the maximum-tolerated dose of cyclophosphamide ( CTX) when administered sequentially with melphalan 60 mg/m(2)/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children wi th recurrent or progressive malignant brain tumors, and to make prelim inary observations on efficacy. Patients and Methods: Nineteen patient s between the ages of 2 and 21 years were enrolled and 18 were assessa ble for effects of therapy. CTX was administered to seven patients at 750 mg/m(2)/d for 4 days, to five patients at 975 mg/m(2)/d, to three patients at 1,200 mg/m(2)/d, and to three patients at 1,500 mg/m(2)/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therap y, time to progression, and survival were monitored. Results: The medi an time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (ran ge, 16 to 60). Four heavily pretreated patients (22%) died of transpla nt-related complications. No dose-limiting, nonhematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs ), and one with ependymoma (one CR). The estimated 1-year survival rat e was 39% (SE 12%). Conclusion: CTX, at a maximum total dose of 6,000 mg/m(2), administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not bee n heavily pretreated. Responses were seen in patients with medulloblas toma and germinomas. Further trials in children with chemosensitive tu mors, with minimal residual disease, are planned. (C) 1996 by American Society of Clinical Oncology.