Current Approaches in Antifungal Prophylaxis in High Risk Hematologic Malignancy and Hematopoietic Stem Cell Transplant Patients

Abstract

Invasive fungal infections (IFIs) pose the most serious infectious risk to patients with hematologic malignancies and in those undergoing hematopoietic stem cell transplantation (HSCT). Invasive candidiasis has an incidence of 8-18% and a mortality of 30-40% in various reports. Invasive aspergillosis has an incidence of 4-15% and an even higher mortality of 60-85% cited in the published literature. IFIs have remained difficult to diagnose in a timely way in neutropenic and immunocompromised patients. A timely diagnosis is essential in promptly initiating antifungal therapy in order to optimize clinical outcomes. Thus, antifungal prophylaxis has an enormous appeal to minimize the threat from IFIs. In this article, the epidemiology and risk factors for IFIs as well as evidence from antifungal prophylaxis clinical trials in certain patient groups with hematologic malignancies are reviewed. Antifungal prophylaxis has been shown to be effective in certain settings. However, concerns about shifts in fungal epidemiology, emergence of resistance, drug toxicities, and drug interactions must be considered in deciding how and in whom to use antifungal prophylaxis.

Antifungal prophylaxis during treatment for haematological malignancies: are we there yet?

“…For prophylaxis of aspergillosis an A‐I graded recommendation is only made for posaconazole in AML and MDS patients receiving chemotherapy, and in HSCT patients with GVHD. Other published guidelines (Cornely et al , 2009; Marr et al , 2009)) and reviews (Slavin et al , 2008; Wirk & Wingard, 2009; Leventakos et al , 2010; Kontoyiannis, 2011)) are broadly in line with the above recommendations.…”

Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies

“…Halo sign or macronodules on chest CT scans are usually found earlier in the course of pulmonary IA while cavitations and air-crescent sign are found later in the course of the disease [21]. Moreover, sinus CT scan findings of fluid or bony erosions are highly suggestive of IFD [11,15,22]. In addition, initiation of antifungal therapy with the presence of an early chest CT scan finding of a halo sign has been associated with improved mortality in invasive pulmonary aspergillosis [23].…”

“…However, tissue specimens are sometimes hard to obtain in patients receiving treatment for hematologic malignancies and HSCT patients due to thrombocytopenia and the potential risk of bleeding complications [15]. Moreover, cultural-based methods have low sensitivity and specificity and are time consuming.…”

Comparison of Posaconazole Versus Weekly Amphotericin B Lipid Complex for the Prevention of Invasive Fungal Infections in Hematopoietic Stem-Cell Transplantation

“…Antifungal prophylaxis has been shown to decrease the risk of IFIs in this patient population (1,5). Posaconazole and lipid formulations of amphotericin B such as amphotericin B lipid complex (ABLC) have been shown to be efficacious in the treatment of IFIs, particularly in high-risk patients with hematologic malignancies or HSCT (6Y13).…”