PHASE-II TRIAL OF HEPARIN-PROPHYLAXIS FOR VENOOCCLUSIVE DISEASE OF THE LIVER IN CHILDREN UNDERGOING BONE-MARROW TRANSPLANTATION

Veno-occlusive disease (VOD) of the liver is an early complication of bone marrow transplantation (BMT), The initial event has been hypothes ized to be an injury to the endothelial cells eventually resulting in postsinusoidal obstruction and hepatic failure, The role of anticoagul ants for the prevention of VOD is controversial, Continuous infusion o f heparin has been reported to be effective in preventing VOD in adult s undergoing myeloablative therapy and BMT, An unblinded, historical c ontrolled study was carried out to assess the safety and efficacy of c ontinuous infusion of low-dose heparin in prevention of VOD in childre n undergoing BMT following myeloablative therapy, Fifty consecutively BMT-treated children (10 months to 18 years 7 months) were enrolled in to the study group and received continuous heparin infusion (100 units /kg/day) from the first day of the preparative regimen to day +30 or u ntil discharge, whichever occurred earlier, These were compared with a control group of 70 patients who received BMT for a variety of disord ers, Patient groups were similar with respect to primary diagnosis, ag e, sex, and baseline organ functions, Heparin was well-tolerated, with only minor grade I-II hemorrhagic episodes occurring in 28 patients ( 56%), compared to 50 patients in the control group (71%) (P = 0.184), Bleeding was significantly less following autologous BMT compared to a llogeneic BMT (P < 0.05), VOD was diagnosed in five patients (10%) com pared to 18 of 70 in the control group (25.7%) (P < 0.05), Analysis of risk factors demonstrated a significantly higher incidence of VOD in patients undergoing allogeneic BMT (matched related, mismatched relate d and matched unrelated), patients older than 15 years of age, and pat ients,vith advanced disease (greater than or equal to 2 CR), In summar y, this phase II trial has demonstrated that continuous heparin infusi on can be safely used prophylactically in children undergoing myeloabl ative therapy and BMT, The incidence of moderate and serious VOD was s ignificantly less compared to historical controls, A future randomized , double-blinded, placebo-controlled phase III trial is, however, requ ired to determine the efficacy of heparin in preventing VOD in childre n undergoing myeloablative therapy and BMT.