Safety and Efficacy of Primary Prophylaxis with Voriconazole in Adult Patients with Acute Leukemia.
Authors: Tomas Jose F. , Delgado Pilar , Garcia-Zueco Juan C. , de Oña Raquel , Estevez Monica , Rezusta A. , Yague D. , Garcia-Cia Jose I. , Iglesias Rebeca , Rubio-Felix Daniel 
Published: October 2019

Abstract
Invasive fungal infections (IFI) remain as an important cause of morbidity and mortality in adult patients with acute leukemia (AL). The incidence of proven or probable mold and yeast infections ranges from 5–24% among this selected high-risk patients. Prophylaxis is a commonly used treatment strategy, because the diagnosis of IFI is difficult and often delayed. A meta-analysis showed that itraconazole was more effective than fluconazole as prophylaxis of IFI, and a recent randomized trial demonstrated that in patients undergoing chemotehrapy for acute myelogenous leukemia (AML) posaconazole prevented IFI more effectively than did either fluconazole or itraconazole. Voriconazole (Vor) is a second-generation triazole with an extended spectrum of activity and is the drug of choice for invasive aspergillosis, the main mould that causes IFI among patients with acute leukemia. The drug is available for intravenous or oral administration and is well tolerated with transient visual disturbances, liver enzyme abnormalities and skin rashes being the most common adverse events reported, that rarely lead to treatment discontinuation. In this pilot study we evaluated Vor as prohylaxis treatment for IFI in 70 consecutive cases that underwent induction chemotherapy treatment for acute leukemia in two Clinical Units of Hematology in Spain.
Methods:Oral prophylaxis with VOR at a fixed dose of 200mg/12h after two loading doses of 400mg was started on the first day of chemotherapy and continued until recovery from neutropenia or until ocurrence of an IFI. Patients who were unable to tolerate orally could receive VOR intravenously. Galactomanan was measured twice a week. HR-CT were performed in selected cases. The primary efficacy end point was the incidence of proven/probable IFI. Secondary end points included treatment success (vs failure) and the ocurrence of emergent mould infections. Treatment failure was defined as the ocurrence of proven/probable IFI; receipt of any other systemic antifungal agent for suspected IFI; discontinuation of the study drug for an adverse event; or withdrawal from the study with no additional follow-up.
Results:From Jan 06 to Feb 07, 70 consecutive cases of AL that received induction chemotherapy for AML(58) or ALL(12) were included in the study. Median age was 57 (20–75). Median days with 0.1x109/L and 0.5x109/L were 16(10–35) and 19(12–38) respectively. Neutropenic fever ocurred in 62 cases (88,5%) and in 53% of them (33/62) a documented bacteria was isolated from the blood cultures. Galactomanan was possitive in only two cases (2,8%). HR-CT findings consisting with IFI were observed in 3 cases. Proven or probable IFI ocurred in 3 cases (A, flavus, A. fumigatus and Fusarium) (4,2%). Treatment failure as defined ocurred in 10 cases (16%).
Conclusions: Prophylaxis with voriconazole was an effective and well tolerated regimen for IFI prevention in adult patients with acute leukemia.