thioguanine-anhydrous and Budd-Chiari-Syndrome

Three children developed acute veno-occlusive disease of the liver following combination chemotherapy for acute myelocytic leukemia. The clinical presentation was similar in all three, with acute onset of hepatomegaly and thrombocytopenia in the absence of significant transaminasemia or icterus. In all three patients, radionuclide imaging with technetium-99m sulfur colloid showed hepatosplenomegaly, decreased liver uptake, and increased splenic activity. The results of liver biopsy established the diagnosis, revealing marked centrilobular congestion with hemorrhage into the spaces of Disse, atrophy of central hepatic cords, and edema of the walls of the central and sublobular veins. Each patient showed marked improvement following temporary cessation of chemotherapy. The diagnosis of veno-occlusive disease is suggested by the triad of: (1) clinical signs and symptoms; (2) scintigraphic findings; and (3) temporal relationship to chemotherapy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Budd-Chiari Syndrome; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Daunorubicin; Drug Therapy, Combination; Female; Hepatic Veins; Humans; Leukemia, Myeloid, Acute; Liver Diseases; Male; Radionuclide Imaging; Thioguanine

Two adult male patients with acute leukemia developed a fatal Budd-Chiari-like illness while receiving 6-thioguanine. Both had previously received cytosine arabinoside. Antemortem and postmortem specimens of liver showed changes characteristic of toxic veno-occlusive disease. Similar findings have been described after ingestion of certain plant alkaloids and after treatment with arsphenamine, urethane, and ionizing radiation to the liver. We are unaware of any published reports of veno-occlusive disease of the liver after treatment with either 6-thioguanine or cytosine arabinoside. Although 6-thioguanine was most likely responsible for this syndrome, it is not possible to eliminate cytosine arabinoside as the causative agent. Since both drugs are occasionally used for benign conditions, physicians should be aware of this possible complication.

Topics: Acute Disease; Adolescent; Aged; Budd-Chiari Syndrome; Chemical and Drug Induced Liver Injury; Cytarabine; Hepatic Veins; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver; Male; Thioguanine