Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Autologous, Non-Purged Peripheral Stem Cell Transplantation for High Risk Neuroblastoma Patients

High-dose chemotherapy (HDC) represents the standard of treatment for high-risk neuroblastoma(NBL), hepatic veno-occlusive disease (VOD) is a common, 10-50% and serious complication of haematological stem cell transplantation (HSCT), with up to 90% mortality rates. We planned study to assess whether the use of prophylactic defibrotide in paediatric patients who were heavily treated with chemo-radiotherapy before transplant, and then underwent autologous HSCT.

Seventeen patients who underwent autologous, unpurged peripheral stem cell transplantation PBSC with a high risk of developing VOD, between January 2003-July 2014, were given Defibrotide prophylaxis 25mg/kg/day for 30 days, commencing on -1 of conditioning regimen. All patients were stratified by INSS stage, age, N-MYC status. All were treated with six cycles of induction chemotherapy, myeloablative intensification, surgery for primary site, radiation therapy to the primary tumour site plus metastatic sites i.e bone metastases including skull. Meta-iodobenzylguanidin treatment as targeted radiotherapy was given on -21 prior to myeloablative chemotherapy. Oral 13-cis retinoic acid was employed on day +90 post-transplant. CD34+ cell mobilization and PBSC collection was carreid out after two-four cycles of induction cycles. Conditioning regimen and stem cell infusion was done following four-six weeks of last chemotherapy cycle, in order to reduce the toxicitiy. Conditioning regimen CEM consisted Carboplatin, Etoposide, Melfalan. There were no toxic deaths. All of the patients receieved antimicrobial prophylaxis and total parenteral nutrition support when was needed. Myeloid engraftment on day+13, erythroid engraftment on day+18 and thrombocyte engraftment was achieved on day +23.

Defibrotide prophylaxis seems to reduce incidence of VOD and is well tolerated. VOD incidence and severity was reduced in the defibrotide group which suggests that defibrotide might be effective in preventing and treating VOD. Sufficiently powered randomised trials are now required to definitively test the role of defibrotide in this setting.