Efficacy and safety of amphotericin B lipid complex in 548 children and adolescents with invasive fungal infections

Background: The safety and efficacy of amphotericin B lipid complex injection (ABELCET; Enzon Pharmaceutical, Piscataway, NJ) was assessed in 548 children and adolescents 0-20 years of age who were enrolled in the Collaborative Exchange of Antifungal Research (CLEAR) registry. To our knowledge, this is the largest series of pediatric patients treated for invasive mycoses with a single agent. All patients had cancer or had received a bone marrow, cord blood or solid organ transplant and were treated with amphotericin B lipid complex for documented or suspected fungal infection. Methods: The CLEAR database was queried for all patients 0-20 years of age from 1996 to 2000. Data gathered included demographic variables, underlying disease type, reasons for the use of amphotericin B lipid complex injection, dosing information, clinical response and renal effects. Results: Most patients were either intolerant of or refractory to conventional antifungal therapy, and almost one-half were neutropenic at treatment onset. Of the 548 patients, 300 (54.7%) were transplant recipients and 393 (71.7%) had received one or more concomitant nephrotoxins. Candida and Aspergillus were the most commonly isolated species in patients with proven or probable infections. Response data were evaluable for 255 of the 285 patients with documented single or multiple pathogens. A complete (cured) or partial (improved) response was achieved in 54.9% of patients, with an additional 16.9% of patients having a stable outcome. Among patients with proven Aspergillus infection, the response rates (cured + improved) were 40.5 and 37.5% in transplant and nontransplant patients, respectively. When stable responses were added, the response rates were 48.6 and 71.9%, respectively. There were few clinically significant deleterious effects on renal function. There was no significant difference between the rates of new hemodialysis versus baseline hemodialysis. Elevations in serum creatinine of >1.5 X baseline and >2.5 X baseline values were seen in 24.8 and 8.8% of all patients, respectively. Conclusions: The safety and efficacy data from this large pediatric population support the use of amphotericin B lipid complex injection for treatment of invasive fungal infections in immunocompromised children and adolescents, including the high risk subgroup of transplant recipients. The overall response rate and safety profile in pediatric patients who were largely intolerant of or refractory to conventional antifungal therapy were consistent with earlier reported findings of smaller trials.