Veno-occlusive disease as a complication of preoperative chemotherapy for Wilms tumor: A clinico-pathological analysis.
BACKGROUND
Vincristine (VCR) and actinomycin D (ACD) form the backbone of chemotherapeutic regimens of Wilms tumor treatment. Veno-occlusive disease (VOD) is a potentially life-threatening complication of ACD.


OBJECTIVE
To investigate the incidence of VOD after preoperative chemotherapy and assess the effect of dose and frequency of administrating ACD on the occurrence of VOD.


METHODS
A single-center retrospective study of patients where liver biopsies were performed after 4 or 8 weeks of preoperative chemotherapy. Patients had localized or metastatic Wilms tumor and were treated according to SIOP 9, 93-1, or 2001 protocol. A correlation was analyzed between histologically confirmed VOD, laboratory parameters, and mode and frequency of ACD administration. Long-term hepatic toxicity was assessed 5 years after the end of therapy.


RESULTS
Ninety-one patients were included in this analysis. Forty-one patients (45.1%) had histological evidence of VOD. The incidence of histologically proven VOD was significantly correlated with single administration of 45 microg/kg ACD (SIOP 2001 protocol) as compared to repeated dosing of l5 microg/kg (P = 0.003). Fifty-two percent of all patients had mild-to-severe abnormal liver enzymes 5 years after accomplishing therapy.


CONCLUSIONS
Despite short-course preoperative chemotherapy regimen, patients are at risk of developing histological VOD. This risk is higher when ACD is administered in a 1-day 45 microg/kg regimen as compared to 3 days l5 microg/kg.
Jagt
Charissa T
CT
Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
Zuckermann
Michelle
M
Ten Kate
Fibo
F
Taminiau
Jan A J M
JA
Dijkgraaf
Marcel G W
MG
Heij
Hugo
H
De Kraker
Jan
J
Verschuur
Arnauld C
AC
D000410:Alanine Transaminase / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003609:Dactinomycin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D015994:Incidence; D007223:Infant; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008099:Liver / Q000000981:diagnostic imaging / Q000201:enzymology / Q000473:pathology; D008297:Male; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D009392:Nephrectomy; D011183:Postoperative Complications / Q000139:chemically induced; D012189:Retrospective Studies; D014463:Ultrasonography; D009396:Wilms Tumor / Q000188:drug therapy* / Q000601:surgery
D003609:Dactinomycin; D015251:Epirubicin; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase