Hepatic veno-occlusive disease in pediatric stem cell recipients:: successful treatment with continuous infusion of prostaglandin E1 and low-dose heparin

Limited data exist on therapeutic options for established hepatic veno-occlusive disease (VOD) in pediatric patients after stem cell transplantation (SCT). In this report, we present data on the successful treatment of VOD in three children following allogeneic SCT and report the duplex ultrasound criteria for the confirmation of the diagnosis and for the evaluation of the treatment progress. All patients were <2 years at the time of transplantation and had received preparative regimens containing busulfan and cyclophosphamide. There were no known pretransplant risk factors for VOD. Allogeneic stem cell transplantation was per formed from a sibling donor for CMML and from unrelated donors for Wiskott-Aldrich syndrome and familial hemophagocytic lymphohistiocytosis (FHL). The onset of first clinical symptoms of VOD (as defined by the Seattle and Baltimore criteria) was relatively late in all three patients (days +19, +20, and +25, respectively). Time from onset of first symptoms until confirmation of diagnosis by serial duplex ultrasound examination was 4-11 days. Duplex ultrasound criteria are as follows: complete change of direction of blood flow in the portal vein, decrease of flow in the hepatic veins, and development of collateral circulation. Treatment was initiated upon confirmation of VOD by continuous infusion of prostaglandin El (initial dose 0.075 mu g/kg/h) in addition to low-dose heparin (100 units/kg/d). Treatment was continued at the maximum tolerated dose of 0.3-0.5 mu g/kg/h of PGE(1). After 9, 14, and 25 days of treatment respectively, normal portal vein flow was restored and treatment could be discontinued. All three patients are alive and well without apparent sequelae.