title: Gemtuzumab ozogamicin-induced sinusoidal obstructive syndrome treated with defibrotide: a case report.
abstract: New treatments for relapse of acute myeloid leukaemia (AML), include gemtuzumab ozogamicin (GO), an anti-CD33 monoclonal antibody. We describe a second case of GO-induced sinusoidal obstructive syndrome (SOS) effectively treated with defibrotide (DF). No stem-cell transplantation was involved. On day 23 after the first GO dose, a patient presented with ascites, weight gain, liver enlargement and pain in the right upper quadrant. Sudden hepatic cytolysis (transaminases at six times the normal range: grade 3) and cholestasis [alkaline phosphatase ALP and gamma-glutamyltransferase (GGT) respectively at four and eight times the normal range: grade 2] were observed but there was no evidence of increase serum bilirubin. Treatment with DF (Prociclide), Crinos; 10 mg/kg/day, or 200 mg, q.i.d.) improved the hepatic abnormality within a few days (serum transaminases decreased from 312 to 103 IU/L for aspartate aminotransferase (AST) and from 141 to 80 IU/L for alanine aminotransferase (ALT) within 3 days ALP increased from 253 to 383 IU/L and gamma-GT from 238 to 417 IU/L 4 days after administration of DF. The clinical and biological features of our case suggest a direct involvement of GO in causing SOS, even when used as monotherapy, without allogenic stem-cell transplantation. Low dose DF (10 mg/kg/day) given early during the development of SOS associated with GO was effective. Unfortunately, in our case the patient eventually died of multi-organ failure probably because of failure of GO.
authors.affiliation: Pharmacy Department, General Hospital Dunkerque, France.
authors.forename: D
authors.initials: D
authors.lastname: Lannoy
authors.forename: B
authors.initials: B
authors.lastname: Decaudin
authors.forename: A
authors.initials: A
authors.lastname: Grozieux de Laguérenne
authors.forename: F
authors.initials: F
authors.lastname: Barrier
authors.forename: J M
authors.initials: JM
authors.lastname: Pignon
authors.forename: M
authors.initials: M
authors.lastname: Wetterwald
authors.forename: P
authors.initials: P
authors.lastname: Odou
mesh_terms: D000368:Aged; D017809:Fatal Outcome; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008297:Male; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use; D013386:Succinates / Q000009:adverse effects*
chemical_list: D005343:Fibrinolytic Agents; D011089:Polydeoxyribonucleotides; D013386:Succinates; C036901:defibrotide; C022014:guanidinoethylmercaptosuccinic acid