Defibrotide in the treatment of children with veno-occlusive disease (VOD): a retrospective multicentre study demonstrates therapeutic efficacy upon early intervention.

ABSTRACT

Veno-occlusive disease (VOD) of the liver is a complication observed particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is a polydeoxyribonucleotide with aptameric activity on endothelium. We evaluated in a retrospective analysis the efficacy of DF in pediatric patients developing hepatic VOD after HSCT.A total of 45 patients between 0.2 and 20 years (median age 8.2 years) with hepatic VOD were treated with DF 22 patients (49%) met risk criteria for severe or progressive disease and 23 (51%) for moderately severe and mild disease. The median duration of DF treatment was 17 days. In all, 34 patients (76%) achieved complete response (CR) with a survival rate of 64% at day 100. CR rate in patients with severe disease was 50% with long-term survival of 36%. The average DF dose in the CR group was 45 mg/kg/day and in the no responder (NR) group 27 mg/kg/day. The use of additional drugs besides DF to treat VOD made no difference in the outcome compared to DF alone. The average interval from diagnosis to start of DF was 1 day in the CR and 5.5 days in NR group. In multivariate analysis, early intervention remained the only significant factor for a CR.