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  • Title: High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study.
    Author: Mahoney DH, Strother D, Camitta B, Bowen T, Ghim T, Pick T, Wall D, Yu L, Shuster JJ, Friedman H.
    Journal: J Clin Oncol; 1996 Feb; 14(2):382-8. PubMed ID: 8636747.
    Abstract:
    PURPOSE: To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy. PATIENTS AND METHODS: Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored. RESULTS: The median 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 (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic 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 rate was 39% (SE 12%). CONCLUSION: CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.
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