title: Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy.
abstract: Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells expressing the CD33 receptor by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin. Treatment of acute myeloid leukemia (AML) with gemtuzumab ozogamicin may result in liver injury. We reviewed the course of 23 patients who were given gemtuzumab ozogamicin for AML that had relapsed after hematopoietic cell transplantation. Liver toxicity was assessed through physical examination, serum tests, histologic examination, and hepatic venous pressure measurements. Liver injury developed in 11 patients after gemtuzumab ozogamicin administration; it was manifested as weight gain, ascites, and jaundice in 7 patients. Seven patients died with persistent liver dysfunction and either multiorgan failure or sepsis at a median of 40 days after gemtuzumab ozogamicin infusion. Portal pressure measurements were elevated in 2 patients. Results of liver histologic examination in 5 patients showed sinusoidal injury with extensive sinusoidal fibrosis, centrilobular congestion, and hepatocyte necrosis. Six patients experienced AML remission that was sustained for at least 60 days after gemtuzumab ozogamicin infusion. In summary, hepatic sinusoidal liver injury developed after gemtuzumab ozogamicin infusion. Histology showed striking deposition of sinusoidal collagen, suggesting that gemtuzumab ozogamicin targets CD33(+) cells residing in hepatic sinusoids as the mechanism for its hepatic toxicity.
authors.affiliation: Gastroenterology/Hepatology Section, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue, Seattle, WA 98109-1024, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Rajvanshi
authors.forename: Howard M
authors.initials: HM
authors.lastname: Shulman
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sievers
authors.forename: George B
authors.initials: GB
authors.lastname: McDonald
mesh_terms: D000208:Acute Disease; D000328:Adult; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001752:Blast Crisis; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001219:Aspartate Aminotransferases; D001663:Bilirubin