Veno-occlusive disease as a complication of preoperative chemotherapy for Wilms tumor: A clinico-pathological analysis

• Published in: Pediatric blood & cancer Vol. 53; no. 7; pp. 1211 - 1215
• Main Authors: Jagt, Charissa T., Zuckermann, Michelle, Ten Kate, Fibo, Taminiau, Jan A.J.M., Dijkgraaf, Marcel G.W., Heij, Hugo, De Kraker, Jan, Verschuur, Arnauld C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-12-2009
• Subjects: actinomycin D; Alanine Transaminase - blood; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Aspartate Aminotransferases - blood; Chemotherapy, Adjuvant - adverse effects; Child; Child, Preschool; Dactinomycin - administration & dosage; Dactinomycin - adverse effects; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Epirubicin - administration & dosage; Epirubicin - adverse effects; Female; Hepatic Veno-Occlusive Disease - chemically induced; Hepatic Veno-Occlusive Disease - epidemiology; Hepatic Veno-Occlusive Disease - pathology; Humans; Incidence; Infant; Kidney Neoplasms - drug therapy; Kidney Neoplasms - surgery; Liver - diagnostic imaging; Liver - enzymology; Liver - pathology; Male; Neoadjuvant Therapy - adverse effects; Nephrectomy; Postoperative Complications - chemically induced; Retrospective Studies; Ultrasonography; veno-occlusive disease and Wilms tumor; Wilms Tumor - drug therapy; Wilms Tumor - surgery
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.22202

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.
Objectives
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 µg/kg ACD (SIOP 2001 protocol) as compared to repeated dosing of l5 µg/kg (P = 0.003). Fifty‐two percent of all patients had mild‐to‐severe abnormal liver enzymes 5 years after accomplishing therapy.
Conclusion
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 µg/kg regimen as compared to 3 days l5 µg/kg. Pediatr Blood Cancer 2009; 53:1211–1215. © 2009 Wiley‐Liss, Inc.