Primary antifungal prophylaxis with low-dose intravenous amphotericin B in hematological malignancies.: Results of a pilot study

Background: Systemic fungal infections are a main cause for morbidity and mortality in patients with hematological malignancies. Up to now, the benefit of antifungal prophylaxis is not satisfactory. Patients and Methods: In patients with hematological malignancies and expected neutropenia less than or equal to 500/mu l lasting 10 or more days, the efficacy and tolerability of low-dose intravenous conventional amphotericin B (cAmB) 0.5 mg/kg 3x week was investigated. The incidence of system ic mycoses was com pa red to a historical group of patients with equally severe neutropenia receiving itraconazole solution for antifungal prophylaxis. For this comparison only patients with neutropenia less than or equal to 100/mu l of 10 days and longer were considered. The known side effects of cAmB were minimized by an intensive protective program. Results: So far, 41 patients with 61 neutropenic episodes entered the study. In 4/43 episodes which are evaluable for prophylactic efficacy, probable Aspergillus pneumonia occurred (9.3%). In 39 patients with very severe neutropenia (less than or equal to 100/mu l greater than or equal to 10 days) the rate was 10.2%. In the historical patient group with 72 episodes of the same minimum duration and severity of neutropenia, the incidence of proven systemic mycoses was 16.7%, of probable mycoses 8.3%, totally 25% (vs. 10.2%; p=0.04), all due to mould infection. For side effects, 49 episodes, in which the full protective treatment was given, were evaluable. Prophylaxis had to be stopped in 5/49 (10%) episodes due to therapy-resistant chili or severe rash. In 3 of the 44 remaining episodes intermittent pretreatment with corticosteroids was necessary, and in 5 patients cAmB was delayed for 1-2 days because of in increase of serum creatinine level (WHO grade I). In all patients serum creatinine later normalized. Conclusion: So far, the incidence of invasive fungal infections decreased under prophylaxis with low-dose cAmB compared with a historical patient group receiving itraconazole solution. Acute infusion-related reactions as well as nephrotoxicity seem to be tolerable with an intensive protective program.