HIGH-DOSE MELPHALAN AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS BONE-MARROW RESCUE FOR RECURRENT PROGRESSIVE MALIGNANT BRAIN-TUMORS IN CHILDREN - A PILOT PEDIATRIC-ONCOLOGY-GROUP STUDY
Dh. Mahoney et al., HIGH-DOSE MELPHALAN AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS BONE-MARROW RESCUE FOR RECURRENT PROGRESSIVE MALIGNANT BRAIN-TUMORS IN CHILDREN - A PILOT PEDIATRIC-ONCOLOGY-GROUP STUDY, Journal of clinical oncology, 14(2), 1996, pp. 382-388
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.