ABLC (Abelcet, The Liposome Company) is a ribbon-shaped liposomal formulation of amphotericin B consisting of dimyristoyl-phosphatidylcholine and dimyristoylphosphatidylglycerol in a 7:3 molar ratio which is especially concentrated in pulmonary tissue. It is known to be safe and effective in presumed and confirmed fungal infections in immunocompromised patients at the dose of 5 mg/kg. There are limited data on its use at lower doses. We explored low-dose ABLC in immunocompromised patients with hématologie malignancies who had fever of unknown origin which had failed to respond to combination antimicrobials, and were presumed to have fungal sepsis. 26 immunocompromised patients (15-70 y, median 44; 17 leukemia, 7 myeloma, 2 lymphoma) received 32 courses of ABLC at the median daily dose of 2 mg/kg rounded off to the nearest vial size (range, 1.3-2.7 mg/kg) after autologous (n=7) or allogeneic (n=8) stem cell transplantation or chemotherapy (n=17). The median neutrophil count at start of ABLC therapy was 0.1 x lO'/L (range, 0-8.6). 14 courses of ABLC had been preceded by conventional amphotericin B and 11 by fluconazole without response. The median days of therapy with ABLC was 6 (range, 1-35). Courses of 4 doses (n=23) were considered évaluable for efficacy and all courses were évaluable for toxicity. 18 courses resulted in complete response, 3 in partial response, and 2 in failure (overall response rate 91%). The 2 failures were switched after 5 and 6 days of ABLC to 3 and 2.5 mg/kg AmBisome for 10 and 6 days respectively, grew Candida and aspergillus from the sputum respectively, and died without responding. The change in serum creatinine from the beginning to the end of therapy was -56 to +54 u.mol/L (median -1). 23 treatment courses had been premedicated with chlorpheniramine/hydrocortisone for the first few days. Infusion-related toxicities comprised rigors (n=9), pyrexia (n=5), hypertension (n=l), and hypotension (n=I); at least one of these toxicities was seen in 9 (28%). These data suggest that low-dose ABLC is very effective empiric anti-fungal therapy in immunocompromised patients with hématologie malignancies.The infusion-related side effects are tolerable, and there is no nephrotoxicity.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - 2000|
ASJC Scopus subject areas
- Cell Biology