Bile duct adenocarcinoma mimicking veno-occlusive disease after autologous bone marrow transplantation for acute leukaemia

Abstract

Summary:A 52-year-old female underwent autologous BMT because of acute myeloid leukaemia FAB M4 in second remission. Since the patient had no HLA-identical sibling she received a purged autologous BM transplant. On day +5 she developed signs of a sepsis syndrome with fluid retention and was treated with broad-spectrum antibiotic therapy. However, her body weight remained high, ascites and an increase of total serum bilirubin and alkaline phosphatase developed. The icterus worsened to a total bilirubin level of 25 mg/100 ml. Sonographic and endoscopic imaging showed a dilated gall bladder but disclosed a post-hepatic cause for the icterus. A transjugular liver biopsy on day +71 revealed severe cholestasis and siderosis. The patient remained aplastic with constantly increased bilirubin levels. On day +73 septic shock syndrome occurred and the patient died of multiorgan failure 3 days later. At autopsy, a highly differentiated bile duct adenocarcinoma at the porta hepatis, so-called Klatskin tumour, was found, explaining the fatal course with intractable cholestasis. Keywords: hepatic VOD; cholestasis; bile duct adenocarcinoma Hepatic veno-occlusive disease (VOD) is a syndrome consisting of weight gain, ascites, increase of bilirubin level, and right upper abdominal quadrant pain with a high rate of lethality. Occasionally it can be accompanied by refractoriness to platelet transfusion. In most cases VOD occurs after allogeneic BMT, and occasionally after high-dose chemotherapy with or without autologous stem cell rescue. Despite a range of prophylactic and therapeutic approaches with administration of heparin and tissue plasminogen activator (tPA), 1 transjugular intrahepatic portosystemic stent- shunt (TIPS) 2-4 and even liver transplantation 5 the prognosis has remained poor.We describe a patient who presented clinically with the signs of severe VOD after autologous BMT for AML with an atypical chronic course and a surprising diagnosis post mortem. Case reportA 52-year-old female patient was referred to our department for BMT. She had AML FAB M4 in second remission. The disease had been diagnosed 16 months earlier and the patient had received induction therapy consisting of DNR, vepeside and Ara-C. Complete remission was achieved. Consolidation therapy with Ara-C followed. Two months after the third consolidation cycle the patient had a relapse. She received reinduction therapy with idarubicin and Ara-C and one course of consolidation therapy prior to BMT. Because the patient had no HLA-identical sibling, autologous BM for transplantation was harvested in second remission 2 months before BMT. The BM was purged by mafosfamide. The CD34 + count after purging was 1.44 × 10 6 /kg. On admission for autologous BMT the patient presented with a Karnofsky score of 100. Clinical examination revealed no pathologic findings. The liver and kidney function was normal.Conditioning consisted of BU 4 mg/kg orally daily divided into four doses, total dose 16 mg/kg and vepeside 60 mg/kg. The patient tolerated the conditioning regi...