title: Tissue plasminogen activator (tPA) as therapy for hepatotoxicity following bone marrow transplantation.
abstract: The treatment of established veno-occlusive disease (VOD) of the liver with tissue plasminogen activator (tPA) has been disappointing. In attempts to improve upon these results we identified a subgroup of patients with consistently elevated bilirubin levels who did not meet conventional criteria for VOD (Susp VOD) but who had a significant risk of later developing clinical VOD. In January 1994 we began to treat patients who developed Susp VOD with tPA rather than waiting until they developed clinical VOD. We now report on the results of the first 37 patients who ultimately developed clinical VOD and received tPA therapy prior to Susp VOD, or at the time they had established VOD. Significant bleeding complications occurred in 13 (35%) patients but resolved with discontinuation of therapy in all but one. We found that patients treated early in the course of hepatotoxicity prior to the development of overt VOD had a significantly higher response rate and 100 day survival than patients treated at the time of established VOD. Given the poor results seen in treating late VOD, we suggest that early treatment with tPA may improve the outcome in patients who develop signs of hepatotoxicity following marrow transplantation.
authors.affiliation: Division of Medicine, Departments of Hematologic Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schriber
authors.forename: B
authors.initials: B
authors.lastname: Milk
authors.forename: D
authors.initials: D
authors.lastname: Shaw
authors.forename: N
authors.initials: N
authors.lastname: Christiansen
authors.forename: M
authors.initials: M
authors.lastname: Baer
authors.forename: J
authors.initials: J
authors.lastname: Slack
authors.forename: H
authors.initials: H
authors.lastname: Tezcan
authors.forename: M
authors.initials: M
authors.lastname: Wetzler
authors.forename: G
authors.initials: G
authors.lastname: Herzig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D018572:Disease-Free Survival; D006470:Hemorrhage; D006504:Hepatic Veno-Occlusive Disease / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006932:Hyperbilirubinemia / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D008875:Middle Aged; D012189:Retrospective Studies; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator