Will high dose chemotherapy followed by autologous bone marrow transplantation supplant cranio-spinal irradiation in young children treated for medulloblastoma?
Cranio-spinal 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 1987. 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 ABMT. Their median age at diagnosis was 23 months (R5-71) 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 twenty 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 three days. After recovery from aplasia, patients with a local relapse received local radiotherapy limited to posterior fossa.


RESULTS
among the 16 patients with measurable disease, 6 CR, 6 PR, 3 NR, were observed following HDC (response rate 75%). One patient was not evaluable. For the 20 patients, the EFS is 50%. Among the surviving patients, the median follow up is 31 months post BMT (R12-82). Ten patients who developed a local relapse or local progression are alive with NED without craniospinal irradiation. Among the 7 patients who developed metastases or progression of metastases, only one is alive. Toxicity was high but manageable: the median duration of granulocytopenia < 0.5 x 109/l and thrombocytopenia < 50 x 10(9)/l was 13 and 41 days respectively. Bacteremia was documented in 4 cases. Grade > 2 mucositis and diarrhea were observed in 60% of patients. One complication-related death occurred 1 month post BMT.


CONCLUSIONS
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.
Dupuis-Girod
S
S
Pediatrics Department, Institut Gustave Roussy, Villejuif, France.
Hartmann
O
O
Benhamou
E
E
Doz
F
F
Mechinaud
F
F
Bouffet
E
E
Coze
C
C
Kalifa
C
C
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002528:Cerebellar Neoplasms / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000401:mortality / Q000532:radiotherapy / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies; D013116:Spinal Cord / Q000528:radiation effects*; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000970:Antineoplastic Agents