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.
Bouligand
J
J
UPRES EA3535, Pharmacology and New Treatments of Cancers, Institut Gustave Roussy, Villejuif, France.
Le Maitre
A
A
Valteau-Couanet
D
D
Grill
J
J
Drouard-Troalen
L
L
Paci
A
A
Hartmann
O
O
Benhamou
E
E
Vassal
G
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005293:Ferritins / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D007223:Infant; D007501:Iron / Q000097:blood; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000601:surgery; D016017:Odds Ratio; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013852:Thiotepa / Q000008:administration & dosage; D014168:Transferrin / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D014168:Transferrin; D003520:Cyclophosphamide; D005293:Ferritins; D013852:Thiotepa; D007501:Iron; D002066:Busulfan; D008558:Melphalan