• Charissa T Jagt, Michelle Zuckermann, Fibo Ten Kate, Jan A J M Taminiau, Marcel G W Dijkgraaf, Hugo Heij, Jan De Kraker, and Arnauld C Verschuur.
• Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.
• Pediatr Blood Cancer. 2009 Dec 15;53(7):1211-5.

BackgroundVincristine (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.ObjectivesTo investigate the incidence of VOD after preoperative chemotherapy and assess the effect of dose and frequency of administrating ACD on the occurrence of VOD.MethodsA 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.ResultsNinety-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.ConclusionDespite 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.

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