High-dose chemotherapy with hematopoietic stem cell rescuein children older than 3 year with medulloblastoma: results of single institution trial

Background: Medulloblastoma (MB) is the most common malignant brain tumor in children, comprises about 20% of all pediatric braintumors. Among average risk MB, survival rate has been reached over 80%. However, in high-risk patients it remains poor. In our trial, we aimed to investigate effectiveness of risk-adapted radiotherapy followed by dose-intense chemotherapy with PBSCs rescue.Methods: 30 patients, 14 with AR disease and 16 with HR were enrolled onto our study from 2007 to 2013. After tumor resection, all patients received risk-adapted craniospinal radiotherapy (23.4 Gy for AR MB and 36 Gy for HR MB, with local boost 54 Gy), followed by 4 cycles of high-dose chemotherapy with PBSC rescue. Each cycle consisted of cyclophosphamide (4000 mg/m2 per cycle), cisplaitn (75 mg/m2 per cycle), and vincristine (2 mg /m2 per cycle). Support with PBSCs was administered after each cycle of chemotherapy. The dose of CD34+ cells was 1,27×106/kg per cycle (range 0,2-2,7×106/kg).Results: 28 of the 30 patients completed all 4 cycles of chemotherapy. There were two (6,7%) toxic related deaths during treatment. Both patients have died for bacterial sepsis. All patients had neutropenia after each cycle of chemotherapy; however, febrile neutropenia was observed in 83% of patients. Most of the toxicities that occurred during high-dose chemotherapy was anticipated. All of the 30 patients required platelet and RBCs transfusion. In our study, 3-year PFS for the 14 AR patients was 77,4±11,5%, for HR patients was 66,1±11,4% with median follow up 56,8±5,6 and 39±4,7 months respectively.Discussion: the results showed that dose-intensive chemotherapy improves PFS in patients with HR MB, but it still worse than in AR MB. Based on our results we can say that future trials for MB treatment should consider molecular and biological features of MB.

medulloblastoma, children, high - dose chemotherapy