Veno-Occlusive Disease of the Liver during Induction Therapy for Acute Lymphoblastic Leukemia

Veno-occlusive disease (VOD) of the liver constitutes a well known complication of high-dose chemotherapy during hematopoietic stem cell transplantation. We present a fatal case of VOD during conventional induction chemotherapy for acute lymphoblastic leukemia. A 51-year-old woman was admitted in our department due to fatigue and malaise since 2 weeks. She was diagnosed with T-acute lymphoblastic leukemia. Liver and lymph nodes were not palpable. Routine biochemistry was within normal range, except a slightly increased lactate dehydrogenase. Induction therapy was started with vincristine, daunorubicin, prednisone, L-asparaginase and methotrexate. On day 12, the patient became slightly icteric (total bilirubin 2.87mg/dl) and complained of epigastric and right upper quadrant pain, vomiting and flatulence. On physical examination, her liver was now palpable and tender. Within the next two days, her clinical status progressively deteriorated with further increase in bilirubin levels, significant hepatomegaly and ascites. As a result, we had to interrupt treatment on day 14 and start antibiotics and parenteral fluid administration. However, on day 17 her clinical status was further aggravated with low-grade fever and increase of body weight by 5kgs, which makes 9% of her original weight. We aspirated 1500cc of ascitic fluid. Laboratory tests revealed pancytopenia, hyperbilirubinemia, mild transaminasaemia and slightly impaired renal function. Coagulation status was normal. Serologic tests for infectious hepatitis (HBV, HCV) were negative. Ultrasound and computed tomography scan of the abdomen revealed hepatomegaly, ascites, patent splenic and portal veins, no mass lesions of the liver and normal appearance of the gallbladder and bile ducts. We administered recombinant tissue plasminogen activator at a dose of 1mg/kg over four days. On day 22, the clinical status of the patient was critical with high fever, and central nervous system involvement with drowsiness, paresis of the hypoglossal and facial nerves, right hemiparesis and hypaesthesia. On day 25, the patient became stuporous, with large abdominal distention and deep jaundice (total/direct bilirubin 34/20mg/dl) and she finally died the next day. To our knowledge, this is the first fatal case of hepatic VOD during induction therapy for acute lymphoblastic leukemia.