URSODIOL PROPHYLAXIS AGAINST HEPATIC COMPLICATIONS OF ALLOGENEIC BONE-MARROW TRANSPLANTATION - A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

Background: Hepatic complications are a major cause of illness and dea th after bone marrow transplantation. Objective: To confirm the result s of a pilot study that indicated that ursodiol prophylaxis could redu ce the incidence of veno-occlusive disease of the liver. Design: Rando mized, double-blind, placebo-controlled study. Setting: Tertiary care teaching hospital. Patients: 67 consecutive patients undergoing transp lantation with allogeneic bone marrow (donated by a relative) in whom busulfan plus cyclophosphamide was used as the preparative regimen and cyclosporine plus methotrexate was used to prevent graft-versus-host disease. Intervention: Before the preparative regimen was started, pat ients were randomly assigned to receive ursodiol, 300 mg twice daily ( or 300 mg in the morning and 600 mg in the evening if body weight was > 90 kg), or placebo. Measurements: Patients were prospectively evalua ted for the clinical diagnosis of veno-occlusive disease, the occurren ce of acute graft-versus-host disease, and survival. Results: The inci dence of veno-occlusive disease was 40% (13 of 32 patients) in placebo recipients and 15% (5 of 34 patients) in ursodiol recipients (P = 0.0 3). Assignment to placebo was the only pretransplantation characterist ic that predicted the development of veno-occlusive disease. The most significant predictor of 100-day mortality was the diagnosis of veno-o cclusive disease. The difference in actuarial risk for hematologic rel apse in patients with chronic myelogenous leukemia and nonhepatic toxi cities between the two groups was not statistically significant (13% i n the ursodiol group and 20% in the placebo group; P > 0.2). Conclusio n: Ursodiol prophylaxis seemed to decrease the incidence of hepatic co mplications after allogeneic bone marrow transplantation in patients w ho received a preparative regimen with busulfan plus cyclophosphamide.