Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021

Abstract

Antifungal prophylaxis can reduce morbidity and mortality from invasive fungal disease (IFD). However, its use needs to be optimised and appropriately targeted to patients at highest risk to derive the most benefit. In addition to established risks for IFD, considerable recent progress in the treatment of malignancies has resulted in the development of new 'at-risk' groups. The changing epidemiology of IFD and emergence of drug resistance continue to impact choice of prophylaxis, highlighting the importance of active surveillance and knowledge of local epidemiology. These guidelines aim to highlight emerging risk groups and review the evidence and limitations around new formulations of established agents and new antifungal drugs. It provides recommendations around use and choice of antifungal prophylaxis, discusses the potential impact of the changing epidemiology of IFD and emergence of drug resistance, and future directions for risk stratification to assist optimal management of highly vulnerable patients.

Diagnosis and Antifungal Prophylaxis for COVID-19 Associated Pulmonary Aspergillosis

“…Among patients without COVID-19, antifungal prophylaxis is often indicated when there will be prolonged neutropenia, typically in the setting of malignancy, chemotherapy, or other immunosuppression [ 50 ]. Medication selection is often between triazole agents, amphotericin B, echinocandins, or combination therapy with voriconazole with an echinocandin, liposomal amphotericin B with an echinocandin, or amphotericin B with a triazole [ 51 ]. Posaconazole has been shown to be effective in reducing the incidence of IPA and mortality among neutropenic patients with acute myeloid leukemia and those with graft-versus-host disease after allogeneic hematopoietic stem cell transplant [ 52 , 53 ].…”

Invasive Aspergillosis and the Impact of Azole-resistance

“…In the last decades, the development of new therapies, such as inhibitors of tyrosine kinase (e.g. ibrutinib) or Janus-kinase, checkpoint-inhibitors, and CAR-modified T-cells (due to the use of steroids and tocilizumab for the prevention of cytokine release syndrome), has also been associated with higher risk for IA [ 7 , 8 , 9 ]. Among solid organ transplant (SOT), lung transplant recipients have the highest risk of IA.…”

Cost-Effectiveness of Posaconazole vs. First-Generation Triazoles for the Prevention of Invasive Fungal Infections Among High-Risk Patients With Hematological Malignancies in China

“…Antifungal prophylaxis for high-risk populations, especially those with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who are undergoing chemotherapy, is reasonable and has been widely recommended as a standard strategy in clinical practice ( 6 – 9 ). Posaconazole, a second-generation triazole with a broad antifungal spectrum, has been strongly recommended in multiple foreign guidelines as the sole first-line agent with the highest level of evidence and recommendation for IFI prevention in high-risk AML or MDS patients ( 6 – 8 ). These recommendations were initially built on the basis of a pivotal randomized controlled trial (RCT), which showed a lower IFI occurrence rate and longer survival time in hematological malignancy patients receiving posaconazole than in those receiving the first-generation triazoles fluconazole or itraconazole ( 10 ).…”