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Elevated Plasma Ferritin and Busulfan Pharmacodynamics During High‐dose Chemotherapy Regimens in Children with Malignant Solid Tumors
Author(s) -
Bouligand J,
Maitre A Le,
ValteauCouanet D,
Grill J,
DrouardTroalen L,
Paci A,
Hartmann O,
Benhamou E,
Vassal G
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100168
Subject(s) - busulfan , medicine , melphalan , cyclophosphamide , pharmacodynamics , hematopoietic stem cell transplantation , gastroenterology , hepatic veno occlusive disease , odds ratio , ferritin , chemotherapy , pharmacology , oncology , transplantation , pharmacokinetics
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. Clinical Pharmacology & Therapeutics (2007) 82 , 402–409; doi: 10.1038/sj.clpt.6100168 ; published online 28 March 2007