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 ACID. Objectives. To investigate the incidence of VOID after preoperative chemotherapy and assess the effect of close and frequency of administrating ACID 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 200 1 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 mu g/kg ACD (SIOP 2001 protocol) as compared to repeated dosing of 15 mu g/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 whey ACD is administered in a 1-day 45 mu g/kg regimen as compared to 3 clays 15 mu g/kg. Pediatr Blood Cancer 2009;53:1211-1215. (C) 2609 Wiley-Liss, Inc