Elevated plasma ferritin and busulfan pharmacodynamics during high-dose chemotherapy regimens in children with malignant solid tumors

Hepatic veno-occlusive disease ( HVOD) is a frequent complication during hematopoietic stem-cell transplantation ( HSCT). A strong relationship has been demonstrated between busulfan exposure and HVOD for busulfan - cyclophosphamide and allogeneic HSCT in adults. Busulfan disposition after the first intake was studied in 77 children treated for solid malignancies with high-dose busulfan-containing regimens and autologous HSCT. Busulfan was combined with cyclophosphamide and melphalan ( n 30), melphalan ( n 27), and thiotepa ( n 20). No relationship was observed between busulfan exposure and HVOD. In contrast, plasma ferritin at baseline was higher in patients with HVOD ( 750 ng/ml ( 20 - 3,110)) compared with those without HVOD ( 189 ng/ml ( 8 - 3,967), P 0.012). Multivariate analysis showed that a ferritin level exceeding 300 ng/ml was the only risk factor for HVOD with an odds ratio of 4.0 ( confidence interval 95% ( 1.5 - 11.2), P 0.0071). A high ferritin level at baseline was explained by the diagnosis of neuroblastoma, related treatments and transfusions.