John Libbey Eurotext

Bulletin du Cancer


High-dose chemotherapy followed by autologous bone marrow transplantation in relapse of medulloblastoma Volume 84, issue 3, Mars 1997


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Service d’oncologie pédiatrique, Institut Gustave-Roussy, rue Camille-Desmoulins, 94800 Villejuif, France.

Craniospinal irradiation is the gold standard treatment used in non metastatic medulloblastoma as prophylaxis against central nervous system (CNS) metastases. However, given the severe late effects caused by this procedure in children under 3 years of age, most pediatric oncologists are currently treating these patients with conventional chemotherapy in order to postpone or even avoid irradiation. In the French Society of Pediatric Oncology (SFOP) this attitude has been adopted since 1990. Among the patients treated without radiotherapy, 20 relapsed while on 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 months) and the relapse occurred at a median time of 6.3 months after the initiation of chemotherapy. Complete surgical removal of the local relapse was the first treatment in 4/20 patients who were not evaluable for response. Sixteen of the 20 patients had measurable disease at the primary site (9 patients), or at metastatic sites (3 patients) or both (4 patients). The conditioning regimen consisted of combination busulfan 600 mg/m2 over 4 days and thiotepa 900 mg/m2 over 3 days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa. Among the 16 patients with measurable disease, 6 complete responses, 6 partial responses, 3 non response, were observed following HDC (response rate 75%). One patient was not evaluable. For the 20 patients, the event free survival (EFS) is 50%. Among the surviving patients, the median follow-up is 39.5 months post BMT (range: 21-92 months). Ten patients who developped a local relapse or local progression are alive with non evidence of disease (NED) without craniospinal irradiation. Among the 7 patients who developped a metastases or progression of metastases, only 1 is alive. Toxicity was high but manageable. One complication-related death occurred 1 month post BMT. With a 75% response rate, this HDC proved to be very efficient in relapsed medulloblastoma. A longer follow-up is necessary to demonstrate whether, after a local relapse, HDC could replace craniospinal irradiation as prophylaxis against CNS metastases.