HIGH-DOSE CHEMOTHERAPY FOLLOWED BY AUTOLO GOUS BONE-MARROW TRANSPLANTATION IN RELAPSE OF MEDULLOBLASTOMA

Craniospinal irradiation is the gold standard treatment used in non me tastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However given the severe late effects caused by thi s procedure in children under 3 years of age, most pediatric oncologis ts are currently treating these patients with conventional chemotherap y in order to postpone or even avoid irradiation. In the French Societ y of Pediatric Oncology (SFOP) this attitude has been adopted since 19 90, Among the patients treated without radiotherapy 20 relapsed while an conventional chemotherapy and were entered in a study of high-dose chemotherapy (HDC) followed by autologous bone marrow transplantation (ABMT). Their median age at diagnosis was 23 months (range: 5-71 month s) and the relapse occurred at a median time of 6.3 months after the i nitiation of chemotherapy. Complete surgical removal of the local rela pse was the first treatment in 4/20 patients who weve not evaluable fo r response. Sixteen of the 20 patients had measurable disease at the p rimary site (9 patients), or at metastatic sites (3 patients) or both (4 patients). The conditioning regimen consisted of combination busulf an 600 mg/m(2) over 4 days and thiotepa 900 mg/m(2) over 3 days. After recovery from aplasia, patients with a local relapse received local r adiotherapy limited to posterior fossa. Among the 16 patients with mea surable disease, 6 complete responses, 6 part ial responses, 3 non res ponse, were observed following HDC (response rate 75%). One patient wa s not evaluable. For the 20 patients, the event free survival (EFS) is 50%. Among the surviving patients, the median follow-zip is 39.5 mont hs post BMT (range 21-92 months). Ten patients who developped a local relapse or local progression are alive with non evidence of disease (N ED) without craniospinal irradiation. Among the 7 patients who develop ped a metastases or progression of metastases, only I is alive. Toxici ty was high but manageable. One complication-related death occurred 1 month post BMT. With a 75% response rate, this HDC proved to be very e fficient in relapsed medulloblastoma. A longer follow-up is necessary to demonstrate whether, after a local relapse, HDC could replace crani ospinal irradiation as prophylaxis against CNS metastases.