Consolidation with a busulfan-containing regimen followed by stem cell transplantation in infants with poor prognosis stage 4 neuroblastoma

Although infants with stage 4 neuroblastoma (NB) usually have a good progno sis, metastatic relapses after 1 year of age and amplification of the N-myc oncogene are established poor prognostic factors. In order to improve the survival of patients with such high-risk factors, we performed consolidatio n with a busulfan (600 mg/m(2))-melphalan (140 mg/m(2))-containing regimen followed by autologous stem cell transplantation (SCT). From 1986 to 1998, 12 patients were treated according to this strategy. Their median age at di agnosis was 9 months (1-11). Consolidation was performed after a metastatic relapse in five children, because of persistent bone metastases in one and as first-line consolidation in six patients whose tumor exhibited N-myc am plification. The 5-year EFS rate is 64.5% (36-85%) with a median follow-up of 92 months (20-126). One toxicity-related death occurred in a very heavil y pretreated patient. Hepatic veno-occlusive disease was the major side-eff ect that occurred in nine of 12 children. This busulfan-melphalan combinati on appears to dramatically improve the prognosis of these high-risk infants with metastatic NB. Given its high toxicity, indications for this consolid ation must be restricted to highrisk infants and a lower dose of busulfan ( 480 mg/m(2)) is recommended in children weighing less than 10 kg.