defibrotide and Leukemia--Myeloid

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.

Topics: Aged; Fatal Outcome; Fibrinolytic Agents; Hepatic Veno-Occlusive Disease; Humans; Leukemia, Myeloid; Male; Polydeoxyribonucleotides; Succinates

Topics: Acute Disease; Aged; Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Female; Gemtuzumab; Hepatic Veno-Occlusive Disease; Humans; Leukemia, Myeloid; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Time Factors

Severe hepatic veno-occlusive disease (VOD) is a recognized complication of autologous and allogeneic stem cell transplantation (SCT) that is often fatal. Defibrotide (DF) is a polydeoxyribonucleotide that has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anticoagulation. Preliminary studies have demonstrated activity for DF in the treatment of VOD, with minimal associated toxicity. In the present study, 40 patients who fulfilled established criteria for VOD were treated with DF on compassionate grounds in 19 European centres; 28 patients met risk criteria predicting progression of VOD and fatality or had evidence of multiorgan failure (MOF), and were defined as 'poor-risk'. DF was commenced intravenously at a median of 14 d (range, -2 d to 53 d) post SCT at doses ranging from 10 to 40 mg/kg. The median duration of therapy was 18 d (range, 2--71 d). Twenty-two patients showed a complete response (CR) (bilirubin < 34.2 micromol/l and resolution of signs/symptoms of VOD and end-organ dysfunction) [CR = 55%, confidence interval (CI) 40--70%] and 17 patients (43%) are alive beyond d +100. Ten poor-risk patients showed a complete response (CR = 36%, CI 21--51%). These results demonstrate that DF is an active treatment for VOD following SCT and a randomized trial is now underway in order to further evaluate its role.

Topics: Acute Disease; Adolescent; Adult; Bilirubin; Breast Neoplasms; Child; Child, Preschool; Female; Fibrinolytic Agents; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Hodgkin Disease; Humans; Infant; Leukemia, Myeloid; Male; Middle Aged; Multiple Myeloma; Polydeoxyribonucleotides; Postoperative Complications; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Outcome