Hepatic Veno-occlusive Disease after Allogeneic Bone Marrow Transplantation in Patients with Leukemia: Risk Factors and Therapeutic Effect of Recombinant Human Tissue Plasminogen Activator

Hepatic veno-occlusive disease(VOD) is a major life-threatening complication of bone marrow transplantation(BMT) caused by high-dose chemotherapy or radiotherapy. The aim of this study is to evaluate the incidence, risk factors, prophylactic effects of low-dose heparin and pentoxifylline(PTX) and therapeutic response to recombinant human tissue plasminogen activator(rt-PA) in VOD patients with leukemia after allogeneic BMT.

Thirty-two consecutive leukemia patients who underwent HLA-matched allogeneic BMT were included in this study. VOD was clinically defined as having two of the following features : hyperbilirubinemia(≥2mg/dL), tender hepatomegaly, unexplained weight gain(>2% from baseline) and/or ascites. Low-dose heparin(l00unit/kg/day, IV) and PTX(1,600mg/day, P0) were administered for the prevention of VOD.

The median age of recipients in this study was 27(17 - 44) years. Patients were treated for the following diseases : 17(53.1%) for acute myeloid leukemia(AML), 10(31.3%) for acute lymphoblastic leukemia(ALL) and 5(15.6%) for chronic myeloid leukemia(CML). Fourteen patients(43.7%) were classified as having high-risk pre-BMT status. Of the 32 consecutive patients undergoing allogeneic BMT, 5(15.6%) developed VOD. A higher risk of developing VOD was associated with pre-BMT disease status(p<0.01). All VOD patients received rt-PA-based thrombolytic therapy and complete resolution was achieved in-4(80.0%) of 5 patients without significant bleeding complications.

Further studies are needed to develop more effective prophylactic and thera-peutic approaches of VOD in patients with high-risk leukemia after allogeneic BMT.