Classification of invasive fungal disease in patients with acute myeloid leukaemia

Abstract

Invasive fungal diseases (IFD) are a major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). Their incidence has risen dramatically in recent years. The diagnosis of IFDs remains difficult, even if the European Organisation for the Research and Treatment of Cancer (EORTC)/Mycosis Study Group (MSG) criteria are applied for study purposes to classify the likelihood of these infections. These criteria have been developed for clinical trials, and their relevance in clinical settings outside a clinical trial remains unknown. We evaluated the impact of the EORTC/MSG criteria and a modification thereof for clinical purposes in patients with AML. We retro-spectively analysed 100 AML patients for the occurrence of IFD. First, EORTC/MSG criteria were applied to classify the patients. Second, a modified version of these criteria already used in clinical trials was used to re-classify the patients. Fifty-seven patients developed an invasive fungal infection. Following the original criteria, 43% were classified as 'possible' IFD, whereas 7% each were classified as 'probable' and 'proven' IFD. After application of the modified criteria, only 9% of the patients remained 'possible' IFD, whereas 41% were 'probable'. The occurrence of 'proven' cases was not altered by the modification and thus remained 7%. The application of modified criteria for the classification of IFD in AML patients leads to a considerable shift from 'possible' IFD (according to conventional EORTC criteria) towards 'probable' IFD. Nevertheless, neither the old EORTC criteria nor their modification was designed for use in clinical practice. As this study underscores the uncertainty in the diagnosis of IFD, the need for a clinically applicable classification is obvious.

Posaconazole prophylaxis – impact on incidence of invasive fungal disease and antifungal treatment in haematological patients

“…The data thus collected were compared to a cohort of 100 high‐risk patients in the preprophylaxis era at our clinic (historical cohort). IFD in this cohort was classified using the original EORTC criteria of 2002 …”

“…Where precise information was lacking, data have been omitted and the case number reduced accordingly. On the basis of a previously reported yearly incidence of IFD of >10%–15%, we agreed to again analyse a number of 100 cases …”

“…We now analysed the effects of posaconazole prophylaxis in this real‐life setting. In a previous study intended to evaluate the applicability of the EORTC/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group‐Consensus ‐criteria (EORTC/MSG) for invasive fungal disease, our centre has performed an analysis of a high‐risk population for the incidence, severity and outcome of IFD . This study also yielded valuable information on the ‘natural history’ of invasive fungal disease in our patient population.…”

Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO)

“…These definitions were developed for use in clinical trials, not for bedside decision‐making. Application of these definitions for bedside decision‐making has been shown to be of limited use . However, when these criteria were applied in clinical practice (in a slightly modified form) to estimate 12‐week mortality in patients with probable or proven invasive aspergillosis (IA) survival was even higher as compared to a clinical trial (82% with various antifungals in clinical practice vs 70.8% for voriconazole, and 57.9% for amphotericin B in a clinical trial, respectively) .…”

A comprehensive diagnostic approach using galactomannan, targeted β‐d‐glucan, baseline computerized tomography and biopsy yields a significant burden of invasive fungal disease in at risk haematology patients

“…In fact, the application of these criteria in clinical practice is a matter of debate (Rieger et al, 2011). Nevertheless, in the absence of a standardized clinical diagnostic approach the EORTC/MSG definitions remain relevant for clinical studies.…”