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

J Bouligand, A Le Maitre, D Valteau-Couanet, J Grill, L Drouard-Troalen, A Paci, O Hartmann, E Benhamou, G Vassal

Journal: Clinical pharmacology and therapeutics 2007;82(4):402-9

PMID: 17392724

Full Text on Ovid Technologies, Inc. View on PubMed

Abstract

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.

Address: UPRES EA3535, Pharmacology and New Treatments of Cancers, Institut Gustave Roussy, Villejuif, France.

DOI: 10.1038/sj.clpt.6100168

Link outs

Subscription / membership required

Full Text Sources:

MeSH Terms: Adolescent, Antineoplastic Combined Chemotherapy Protocols, Busulfan, Child, Child, Preschool, Cyclophosphamide, Female, Ferritins, Hematopoietic Stem Cell Transplantation, Hepatic Veno-Occlusive Disease, Humans, Incidence, Infant, Iron, Male, Melphalan, Neoplasms, Odds Ratio, Prospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, Thiotepa, Transferrin, Transplantation, Homologous, Treatment Outcome