Amphotericin B and Itraconazole as Empirical Antifungal Therapy in Children with Acute Leukemia with Neutropenic Fever.

Purpose: Fungal infections are one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B (ABV) and itraconazole (ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines (IL-4, IL-1Ra) by ABV and ITZA.

Methods: From October 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-1β, TNF-α, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines.

Results: Empirical antifungal agents were given to 37 patients (ABV 20, ITZA 17), and 30 patients (ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-1β was increased in ABV treatment group and the ratio of IL-1Ra/IL-1β is markedly decreased in ABV treatment group while increased in ITZA group.

Conclusions: ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.