Continuously infused amphotericin B deoxycholate for primary treatment of invasive fungal disease in acute myeloid leukaemia.

Abstract

Continuous administration of amphotericin B deoxycholate over 24hours (24h-D-AmB) is better tolerated than rapid infusions. However, toxicity and outcome have not been assessed in a homogenous patient population with acute myeloid leukaemia (AML). We retrospectively analysed renal function and outcome in all adult patients with AML undergoing intensive chemotherapy between 2007 and 2012 at our institution. We compared a patient group with exposure to 24h-D-AmB to a patient group without exposure to 24h-D-AmB. One hundred and eighty-one consecutive patients were analysed, 133 (73.5%) received at least 1 dose of 24h-D-AmB, and 48 (26.5%) did not. Reasons for 24h-D-AmB initiation were invasive fungal disease (IFD) in 63.5% and empirical treatment for febrile neutropenia in 36.5% of the cases. Most patients with IFD received an oral triazole drug at hospital discharge. Baseline characteristics were well matched. Amphotericin B deoxycholate over 24hours was given for a median 7days (interquartile range 3-13). Peak creatinine concentration was higher in the 24h-D-AmB-group (104.5 vs. 76μmol/L, P<.001) but normalized within 1month after therapy (65.5 vs. 65μmol/L, P=.979). In neither of the 2 groups, end-stage renal disease occurred. There was no difference in 60-day survival (90% vs. 90%) and 2-year survival (58% vs. 58%). Invasive fungal disease partial response or better was observed in 68% of the patients. We conclude that antifungal therapy with continuously infused amphotericin B deoxycholate is safe in patients with AML. An antiinfective strategy based on 24h-D-AmB in first line followed by an oral triazole compound represents an economically attractive treatment option.