Introduction.Despite progress obtained with current treatments,the event-free survival of high-risk neuroblastoma(HR-NB)patients does not exceed 40-50% and the prognosis in refractory or relapsed patients is poor,still representing a challenge for pediatric oncologist.Therapeutic Iodine-131 meta-iodobenzylguanidine(Th-131I-MIBG) is a recognized safe and potentially effective treatment in NB.Materials.In this retrospective study,we report outcome of 28 MIBG-avid NB patients with advanced disease,because refractory or relapsed,underwent,from 1996 to 2014,to Th-131I-MIBG administered shortly before(median of 17 days) high-dose chemotherapy with Busulfan and Melphalan(HD-BuMel) and autologous stem cell transplantation(ASCT)at Gaslini Institute in Genoa,with the aim to analyze feasibility,safety and efficacy of this approach.Results.Engraftment occurred in all patients after a median of 14(11-29)and 30 days(13-80)from ASCT for neutrophil and platelet respectively.No treatment-related deaths were observed.The main high grade(3-4)toxicity observed was oral and gastrointestinal mucositis in 78.6% and 7.1% of patients respectively,while high grade hepatic toxicity was observed in 10.7%;two patients developed veno-occlusive-disease(7.1%),completely responsive to defibrotide.Hypothyroidism was the main late complication occurred in 9 patients(31.1%).After Th-131MIBG and HD-BuMel, 19 patients(67.8%) showed an improvement of disease status.Over a median follow-up of 15.9 years,the 3-year and 5-year overall survival(OS)probability were 53%(CI 0.33-0.69)and 41%(CI 0.22-0.59)and the 3-year and 5-year rates of cumulative risk of progression/relapse were 64%(CI 0.47-0.81)and 73%(CI 0.55-0.88),respectively.MYCN amplification emerged as the only risk factor significantly associated with OS(HR 3.58;p0.041).Conclusion.Th-131I-MIBG administered shortly before HD-BuMel turned out to be a safe and effective regimen,suggesting it should be included in a sequential approach in patients with advanced MIBG-avid NB.These patients could be benefit to be manage in centers with proven expertise in these treatments.