TREATMENT OF SEVERE VENOOCCLUSIVE DISEASE WITH DEFIBROTIDE - COMPASSIONATE USE RESULTS IN RESPONSE WITHOUT SIGNIFICANT TOXICITY IN A HIGH-RISK POPULATION

Hepatic veno-occlusive disease (VOD) is the most common of the regimen -related toxicities accompanying stem cell transplantation (SCT). Desp ite aggressive therapies, including the combination of tissue plasmino gen activator (t-PA) and heparin, severe VOD is almost uniformly fatal . Defibrotide (DF) is a polydeoxyribonucleotide with activity in sever al vascular disorders and, unlike t-PA and heparin, produces no system ic anticoagulant effects. Nineteen patients who developed severe VOD a fter SCT were treated with DF on a compassionate-use basis. Patients h ad clinically established VOD and met risk criteria predicting progres sion and fatality. At the initiation of DF, all 19 patients had eviden ce of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 pati ents had renal insufficiency (5 dialysis dependent), 14 required oxyge n supplementation, and encephalopathy was present in 8 patients. Begin ning a median of 6 days after diagnosis of VOD, DF was administered in travenously in doses ranging from 5 to 60 mg/kg/d for a planned minimu m course of 14 days. In no case was DF discontinued for attributable t oxicity. No severe hemorrhage related to DF administration was observe d. Resolution of VOD (bilirubin <2 mg/dL with improvement in other sym ptoms and signs) was seen in 8 patients (42%). Six of 8 responders sur vived past day +100, contrasted with the 2% predicted survival reporte d in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling end warrant further evaluation. (C) 1998 by The American So ciety of Hematology.