Veno-occlusive disease, which developed in 54% of bone marrow transplant recipients, is frequently associated with renal and cardiopulmonary failure. Pretransplant transaminase elevations, use of high-dose cytoreductive therapy, and persistent fever during cytoreductive therapy are independent predictors of severe VOD.

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The course of VOD after cytoreductive therapy can be predicted by knowing the serum bilirubin and weight gained within 1 to 2 weeks of transplantation. Probability estimates derived from patient data are highly specific and moderately sensitive. Such probability estimates may be useful when considering potentially risky interventions to treat VOD, such as recombinant human tissue plasminogen activator.

We conducted a phase I/II trial of prostaglandin E1 (PGE1) for the prevention of hepatic venocclusive disease (VOD). Twenty-four patients at high risk for VOD received PGE1 at four dose levels ranging from 1.25 to 10 ng/kg/min. Severe toxicity was experienced at all dose levels and was manifested as cutaneous erythema and desquamation, severe pain in dependent extremities, fluid retention and grade 4 oedema, or hypotension. In 12/24 patients, PGE1 administration was stopped prior to day 15 due to severe toxicity attributed to the drug. Three of 12 patients who received PGE1 for the entire course of treatment and 9/12 patients whose PGE1 was stopped prior to day 15 developed severe toxicity which was attributed to PGE1 (P = 0.039). Severe toxicity attributed to PGE1 was not related to either PGE1 concentration or PGE1 clearance. Six of 12 patients whose PGE1 infusion was stopped prior to day 15 and 2/12 patients who received PGE1 for the full course of treatment developed severe VOD (P = 0.19). We conclude that PGE1 causes significant toxicity in patients undergoing marrow transplantation. The ability of PGE1 to prevent severe VOD in patients at high risk remains unproven.

Seven patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic venocclusive disease (VOD) that developed after bone marrow transplantation for hematologic malignancy. Recombinant human tPA (10 mg/d x 2 days) and heparin (1,000 U bolus followed by continuous intravenous infusion of 150 U/kg/d x 10 days) were begun a median of 9 days (range, 4 to 18 days) posttransplant. The median total serum bilirubin and percent weight gain from baseline were 19.4 mg/dL (range, 14.6 to 34.9 mg/dL) and 9.1% (range, 1% to 18.5%), respectively, at the start of tPA administration. Five patients responded to therapy with prompt reduction in total serum bilirubin within 96 hours of starting tPA. Three patients are alive 178 to 379 days posttransplant without evidence of VOD. No patient had significant hemorrhagic complications with tPA. We conclude that recombinant human tPA can be administered to patients with severe VOD at the dosage described. Whereas preliminary data suggests that recombinant human tPA can alter the natural history of severe VOD, further study is necessary to determine its efficacy.

The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.

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