Veno-occlusive disease of the liver in children treated for Wilms tumor.
BACKGROUND
Hepatotoxicity consistent with the clinical diagnosis of veno-occlusive disease (VOD) of the liver has been suspected after conventional anti-cancer chemotherapy in children.


METHODS
To establish the incidence of hepatotoxicity and its relationship with VOD, we analyzed toxicity data obtained on 511 children affected by Wilms tumor and treated according to the SIOP-9 protocol. They all received pre- and postnephrectomy chemotherapy using dactinomycin (AD) and vincristine (VCR) +/- other drugs +/- radiotherapy according to surgical stage and histology.


RESULTS
Sixty-four patients suffered at least one episode of hepatotoxicity and 41 satisfied the criteria for a clinical diagnosis of VOD. In this latter group, toxicity occurred during preoperative treatment in 15 patients and was confirmed histopathologically in 9 of the 16 liver biopsies obtained. There was a higher percentage of children aged less than 1 year at diagnosis in the VOD group than in the other patients (24% vs. 11.4%). The degree of liver damage in the younger patients seems important, as suggested by a higher increase in transaminases. VOD developed in 12% of the 68 irradiated children vs. 7% in the non-irradiated group. Statistical analysis showed an increased risk of VOD in younger patients (p < 0.001) and in those receiving radiotherapy (p < 0.001). All patients recovered after 6-180 days using supportive therapy only.


CONCLUSIONS
(1) 8% of children treated according to the SIOP-9 protocol, developed hepatotoxicity consistent with VOD. Excluding patients who received radiotherapy, the incidence was 6%. These figures are much higher than in earlier reports, though different diagnostic criteria were used. (2) Chemotherapy with AD and VCR seems to be a major cause of VOD. (3) Risk factors are young age and concomitant radiotherapy. (4) VOD does not prejudice positive outcome for these patients.
Bisogno
G
G
Department of Pediatrics, University of Padova, Italy.
de Kraker
J
J
Weirich
A
A
Masiero
L
L
Ludwig
R
R
Tournade
M F
MF
Carli
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000628:therapy*; D008099:Liver / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D009396:Wilms Tumor / Q000628:therapy*
D003609:Dactinomycin; D014750:Vincristine