European guidelines for primary antifungal prophylaxis in adult haematology patients: summary of the updated recommendations from the European Conference on Infections in Leukaemia

Abstract

The European Conference on Infections in Leukaemia (ECIL) updated its guidelines on antifungal prophylaxis for adults using the grading system of IDSA. The guidelines were extended to provide recommendations for other haematological diseases besides AML and recipients of an allogeneic haematopoietic stem cell transplantation (HSCT). Posaconazole remains the drug of choice when the incidence of invasive mould diseases exceeds 8%. For patients undergoing remission-induction chemotherapy for AML and myelodysplastic syndrome (MDS), fluconazole can still offer an alternative provided it forms part of an integrated care strategy that includes screening with biomarkers and imaging. Similarly, aerosolized liposomal amphotericin B combined with fluconazole can be considered for patients at high risk of invasive mould diseases but other formulations of the polyene are discouraged. Fluconazole is still recommended as primary prophylaxis for patients at low risk of invasive mould diseases during the pre-engraftment phase of allogeneic HSCT whereas only a moderate recommendation could be made for itraconazole, posaconazole and voriconazole for patients at high risk. Posaconazole is strongly recommended for preventing invasive mould disease post-engraftment but only when graft-versus-host disease (GvHD) was accompanied by other risk factors such as its severity, use of an alternative donor or when unresponsive to standard corticosteroid therapy. The need for primary prophylaxis for other patient groups was less clear and should be defined by the estimated risk of invasive fungal disease (IFD).

Aspergillus flavus Disseminated Infection in Paediatric Acute Lymphoblastic Leukaemia: A Case Report

“…Our patient developed a disseminated Aspergillus flavus infection with multiple subcutaneous, muscular and parenchymal lesions. IA is an unexpected finding in paediatric ALL at the beginning of the first line therapy, as we observed in our patient: no antifungal prophylaxis is usually recommended in paediatric ALL [18][19][20]. Even if patient's personal history was positive for a traumatic event, disseminated IA was more likely the consequence of fungal vascular migration from an initial pulmonary site than direct inoculation of Aspergillus flavus into the skin, also considering that no cutaneous laceration was detected or referred.…”

Characteristics and risk factors for mortality of invasive non‐Aspergillus mould infections in patients with haematologic diseases: A single‐centre 7‐year cohort study

“…Invasive fungal infections (IFIs) remain a leading cause of morbidity and mortality in patients with haematologic diseases . Antifungal prophylaxis has already been proven to be clinically effective in preventing IFIs in high‐risk patients with haematologic diseases, and primary antifungal prophylaxis (PAP), particularly mould‐active azole in high‐risk groups is now a standard protocol in international guidelines . These recent advances in the use of PAP during chemotherapy and haematopoietic stem cell transplantation (HSCT) have reduced the number of IFIs and improved the survival of high‐risk patients .…”

Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations

“…Epidemiology studies have demonstrated that mold infections (e.g., Aspergillus species) are more prevalent in neutropenic hematologic malignancy populations . Prophylactic use of antifungals with a broader spectrum of activity, such as voriconazole, reduce the incidence of invasive fungal disease, although breakthrough infections are commonly observed …”

“…Voriconazole is an effective antifungal prophylactic and is recommended as primary treatment for invasive aspergillosis in immunocompromised patients . Voriconazole displays highly variable nonlinear pharmacokinetics, and there is a strong correlation between voriconazole plasma trough concentrations and clinical outcomes in those with invasive fungal infections .…”