Antineoplastics
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Reactions 1235 - 17 Jan 2009 S Antineoplastics Fatal veno-occlusive disease: case report A 51-year-old woman developed fatal veno-occlusive disease following induction therapy with vincristine, daunorubicin, prednisone, asparaginase and methotrexate for T-acute lymphoblastic leukaemia. The woman received vincristine 1.5 mg/m 2 on days 1 and 8, daunorubicin 45 mg/m 2 daily for 2 days, prednisone 40 mg/m 2 daily, asparaginase 6000 U/m 2 every second day and intrathecal methotrexate 12.5mg every 14 days. She became slightly jaundiced on day 12, with a total bilirubin level of 2.87 mg/dL, and experienced epigastric and right upper quadrant pain, flatulence and vomiting. Her liver was tender and palpable on examination. Her condition deteriorated within the following 2 days, with further increases in bilirubin (total 5.6/direct 3.8 mg/dL), ascites and significant hepatomegaly. On day 14, the woman’s treatment was interrupted and she received fluids and antibacterials. On day 17, a low- grade fever and a 5kg bodyweight increase were apparent. 1500cc of ascitic fluid was aspirated. Laboratory investigations revealed the following: pancytopenia (WBC count 800/µL, platelets 40 000/µL, Hb 9.6), mild transaminasaemia (AST 70 U/L, ALT 68 U/L), slightly impaired renal function (creatinine 1.8 mg/dL, urea 90 mg/dL) and total and direct bilirubin levels of 10.3 and 7.9 mg/dL, respectively. Tests for an infectious cause were negative. Abdominal CT and ultrasound showed ascites and hepatomegaly. She received alteplase for 4 days. Her status was critical on day 22: she had a fever, CNS involvement with drowsiness, hypoglossal and facial nerve paresis, right hemiparesis and hypaesthesia. She became stuporous on day 25, with abdominal distension and total and direct bilirubin levels of 34 and 20 mg/dL, respectively. She died the following day. Author comment: "[W]e do not have any clues to attribute [veno-occlusive disease] to a specific chemotherapeutic agent among those that we used. Asparaginase is a well-known hepatotoxic agent but it has never been described to cause veno-occlusive liver disease with induction doses. Perhaps, the fact that vincristine was the only common agent between our case and [another] case might indicate this was the cause." Papadopoulos A, et al. Veno-occlusive disease of the liver during induction therapy for acute lymphoblastic leukemia. International Journal of Hematology 88: 441-442, No. 4, Nov 2008 - Greece 801135080 1 Reactions 17 Jan 2009 No. 1235 0114-9954/10/1235-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
Transcript of Antineoplastics
Reactions 1235 - 17 Jan 2009
SAntineoplastics
Fatal veno-occlusive disease: case reportA 51-year-old woman developed fatal veno-occlusive
disease following induction therapy with vincristine,daunorubicin, prednisone, asparaginase and methotrexatefor T-acute lymphoblastic leukaemia.
The woman received vincristine 1.5 mg/m2 on days 1 and8, daunorubicin 45 mg/m2 daily for 2 days, prednisone40 mg/m2 daily, asparaginase 6000 U/m2 every second dayand intrathecal methotrexate 12.5mg every 14 days. Shebecame slightly jaundiced on day 12, with a total bilirubinlevel of 2.87 mg/dL, and experienced epigastric and rightupper quadrant pain, flatulence and vomiting. Her liver wastender and palpable on examination. Her conditiondeteriorated within the following 2 days, with furtherincreases in bilirubin (total 5.6/direct 3.8 mg/dL), ascitesand significant hepatomegaly.
On day 14, the woman’s treatment was interrupted andshe received fluids and antibacterials. On day 17, a low-grade fever and a 5kg bodyweight increase were apparent.1500cc of ascitic fluid was aspirated. Laboratoryinvestigations revealed the following: pancytopenia (WBCcount 800/µL, platelets 40 000/µL, Hb 9.6), mildtransaminasaemia (AST 70 U/L, ALT 68 U/L), slightlyimpaired renal function (creatinine 1.8 mg/dL, urea90 mg/dL) and total and direct bilirubin levels of 10.3 and7.9 mg/dL, respectively. Tests for an infectious cause werenegative. Abdominal CT and ultrasound showed ascitesand hepatomegaly. She received alteplase for 4 days. Herstatus was critical on day 22: she had a fever, CNSinvolvement with drowsiness, hypoglossal and facial nerveparesis, right hemiparesis and hypaesthesia. She becamestuporous on day 25, with abdominal distension and totaland direct bilirubin levels of 34 and 20 mg/dL, respectively.She died the following day.
Author comment: "[W]e do not have any clues to attribute[veno-occlusive disease] to a specific chemotherapeutic agentamong those that we used. Asparaginase is a well-knownhepatotoxic agent but it has never been described to causeveno-occlusive liver disease with induction doses. Perhaps,the fact that vincristine was the only common agent betweenour case and [another] case might indicate this was thecause."Papadopoulos A, et al. Veno-occlusive disease of the liver during inductiontherapy for acute lymphoblastic leukemia. International Journal of Hematology 88:441-442, No. 4, Nov 2008 - Greece 801135080
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Reactions 17 Jan 2009 No. 12350114-9954/10/1235-0001/$14.95 © 2010 Adis Data Information BV. All rights reserved
