Prophylaxis for aspergillosis in patients with haematological malignancies: pros and cons

Abstract

Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. Nevertheless, invasive fungal infections (IFI) represent a major hindrance to the favorable outcome of patients with hematologic malignancies. According to these observations, an appropriate prevention of IFI occurring in hematologic patients should be considered of paramount importance. However, the wide use of antifungal agents may facilitate the emergence of resistance and may be associated to the occurrence of severe adverse events and eventually may significantly increase the cost of therapeutic procedures. Areas covered: The aim of present review is to analyze advantages and disadvantages of primary antifungal prophylaxis (PAP) in hematologic patients. Expert commentary: Patients with AML/MDS undergoing intensive chemotherapy and patients receiving stem cell transplantation are at high risk of IFI, and therefore may benefit form PAP, although several additional factors should be carefully evaluated in our decision-making approach, including the local epidemiology and the prompt availability of diagnostic facilities. The advent of new treatment options for hematologic patients such as target therapies might facilitate the rise of new risk categories so far underestimated.

Liposomal amphotericin B—the present

“…voriconazole, posaconazole) are inhibitors of this cytochrome system, resulting in the potential for important drug–drug interactions that can cause serious haematological and extra-haematological toxicities if administered simultaneously. 38 This presents haematologists with a serious dilemma of how best to balance optimal antineoplastic treatment with the need for antifungal prophylaxis. Usually, anti-leukaemic chemotherapy is prioritized, but this results in the possibility of an increased risk of an IFI, as reported in a recent study with venetoclax.…”

Updates in infection risk and management in acute leukemia

“…Fluconazole is effective in decreasing Candida infection in transplantation and in patients with graft-versus-host disease, but studies have not shown benefit in preventing invasive mold infections. [20][21][22] Voriconazole is a second-generation triazole that has activity against some opportunistic molds and is a first-line agent for treatment of invasive aspergillosis. Voriconazole has not been approved for use as primary prophylaxis, with studies showing a non-statistically significant trend toward decreased IFI incidence compared with fluconazole.…”

“…23 Voriconazole has excellent bioavailability, although use is complicated by toxicities and drug-drug interactions. 21 Posaconazole is another second-generation, extendedspectrum triazole with activity against Candida and Aspergillus spp, as well as other invasive molds including Fusarium and Mucorales. In several studies, including a multicenter randomized trial, prophylaxis with posaconazole in neutropenic patients with AML or myelodysplastic syndrome receiving induction chemotherapy significantly reduced the rate of IFIs (2% vs 8%; P < .001) and showed survival benefit (P = .04) when compared with fluconazole and itraconazole.…”

“…33 Although mold-active antifungal prophylaxis has become standard of care during neutropenic periods of most AML treatment regimens, there is no similar standardized recommendation during acute lymphoblastic leukemia (ALL) treatment. Patients with ALL are at intermediate to high risk, with the rate of IFIs ranging between 3% and 12%, 21 with higher rates in patients with longer duration of neutropenia, absence of antifungal prophylaxis, and relapsed disease. The strong inhibition of CYP3A4 by mold-active azoles can lead to significant toxicity when administered with several chemotherapy classes, particularly vinca alkaloids and alkylating agents, and targeted therapies such as tyrosine kinase (TK) inhibitors, which are mainstays in the chemotherapy regimens for ALL.…”

Disseminated Geosmithia argillacea Infection in a Patient with Ph-Positive Acute Lymphoblastic Leukemia. Case Report and Literature Review

“…Several studies, most of which published over the last five years, analyzed the rate of IFI in patients with acute lymphoblastic leukemia (ALL), showing an overall incidence of mold infections ranging between 3 and 12% [ 10 ].…”