Low-dose amphotericin B lipid complex for the treatment of persistent fever of unknown origin in patients with hematologic malignancies and prolonged neutropenia.
We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg/kg/day) in 30 persistently febrile (>38 degrees C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (<0.5 x 10(9)/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 micromol/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.
Martino
R
R
Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 27220rmb@comb.es
Subirá
M
M
Domingo-Albós
A
A
Sureda
A
A
Brunet
S
S
Sierra
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005335:Fever of Unknown Origin / Q000188:drug therapy* / Q000209:etiology; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications*; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D000666:Amphotericin B