Summary:Mylotarg (gemtuzumab zogamicin) is a conjugated monoclonal antibody that has recently become available for use in patients with relapsing or refractory acute myeloid leukemia. Reversible hepatotoxicity is common after administration. We describe the first report of hepatic veno-occlusive disease (HVOD) developing after Mylotarg infusion in a patient who underwent hematopoietic stem cell transplantation 8 months earlier. In the last few years, antibody-targeted therapy has emerged as an effective and encouraging treatment for patients with acute myeloid leukemia. Mylotarg (gemtuzumab zogamicin) (Wyeth-Ayerst Laboratories, Philadelphia, PA, USA) consists of recombinant humanized anti-CD33 monoclonal antibody conjugated to an antitumor antibiotic (calicheamicin). Mylotarg-induced remissions have been observed in patients with refractory or relapsed acute myeloid leukemia. 1 Reversible increases in levels of serum bilirubin and aminotransferases are common complications. 2 We describe a patient in whom hepatic venoocclusive disease (HVOD) developed after infusion with Mylotarg. Case reportA 67-year-old woman with acute myeloid leukemia (M5A, normal cytogenetics) received induction chemotherapy with standard doses of idarubicin and cytarabine, followed by consolidation treatment with these agents. Intensification chemotherapy with high-dose cytarabine was given for three cycles. The patient had a relapse after 15 months and was treated by reinduction with idarubicin and cytarabine before undergoing autologous hematopoietic stem cell transplantation (after conditioning with cyclophosphamide and total body irradiation). The patient underwent transplantation without complications but unfortunately had a second relapse 8 months later. Intravenous Mylotarg was given shortly after the second relapse (9 mg/m 2 for two doses 14 days apart). The patient experienced epigastric pain 6 days after the initial drug infusion. On examination, she had right upper quadrant tenderness and abdominal distention. Bilirubin and alkaline phosphatase levels were normal, and transaminases were elevated by less than two-fold. Abdominal ultrasound at the time revealed new diffuse thickening of the gallbladder wall and sludge. Hepatic and portal veins were patent on ultrasound. A previous abdominal computed tomography (CT) scan 1 month prior to Mylotarg infusion was normal (Figure 1). Ten days after Mylotarg administration, abdominal CT revealed the development of ascites (Figure 2). A subsequent CT 1 month after the initial drug infusion showed increasing ascites, a new diffuse abnormal enhancement pattern, and attenuation of hepatic veins (Figure 3). Abdominal paracentesis performed to evaluate the patient's ascites revealed a transu- Figure 1 Normal computed tomography scan of the abdomen 34 days prior to Mylotarg infusion.
serum and urinary samples. The investigators should have measured and compared serum and urinary metabolites with other biomarkers including neutrophil gelatinase-associated lipocalin (NGAL). Serum concentrations of NGAL increase before those of sCr and help in the early detection of AKI in cirrhosis. (2) Increase in metabolites (e.g., kynurenate, tripeptides, and tetrapeptides) is not specific for patients with liver diseases and renal dysfunction. (3) It is not clear how the cutoff was set for determination of mean decrease in accuracy (MDA). For example, urinary kynurenate has an MDA of 30 in patients with AKI and 21 in those requiring dialysis. Whether a difference in MDAs has any correlation with disease state needs further investigation.The study should be more focused in patient selection by including only those with a high risk of developing severe and irreversible AKI and need for dialysis. These include patients with acute-onchronic liver failure, bacterial sepsis, complicated ascites, and acute variceal bleed. (4) Response to AKI determines need for dialysis. The clinical outcomes of patients with volume responsive mild prerenal AKI related to diuretic use are vastly different from those of patients with nonresponsive hepatorenal syndrome. Thus, we need to determine the relationship of serum and urinary metabolites with the type and severity of AKI as well as response of AKI. Timing of dialysis in the study was also not uniform across the centers. Finally, it would be interesting to know whether metabolomics-related outcomes are applicable for incident AKI in patients with cirrhosis and underlying chronic kidney disease.Author Contributions: A.J. was responsible for writing the manuscript and critical analysis. S.S. was responsible for critical analysis.
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