Low-Dose Amphotericin B Lipid Complex for the Treatment of Persistent Fever of Unknown Origin in Patients with Hematologic Malignancies and Prolonged Neutropenia

Abstract

We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg/kg/day) in 30 persistently febrile (>38°C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (<0.5 × 10⁹/l) adult patients with hematologic malignancies. The median age was 45 years (range 18–67), most (60%) had an acute leukemia and all had fever of unknown origin (FUO). The total duration of neutropenia was a median of 17 days (range 9–33), and the total number of days with fever 10 days (range 6–39). Seven patients experienced mild-to- moderate infusion-related adverse events (IRAE). The serum creatinine and urea increased from baseline to end of therapy in 76 and 63% of cases, but the maximum levels reached were <130 µmol/l and <11 mmol/l, respectively, in all cases. Liver enzymes showed modest but significant increases in most patients during therapy, while bilirubin decreased in 74% of cases. Response to treatment (defervescence within 6 days without developing a fungal or nonfungal infection) was seen in 22 cases (73%, 95% CI 58–89%), while 8 episodes were considered treatment failures: 2 due to persistent FUO, 1 withdrew due to IRAE, 2 developed nonfungal infections and 3 developed a presumed or definite invasive mycosis. We conclude that low-dose ABLC is very safe and well tolerated and seems as effective as c-AmB for this indication. Thus, randomized trials at this dose level appear justified to demonstrate any real benefit over c-AmB or other lipid formulations for the treatment of FUO in neutropenic patients.