PS1280 FUNGAL INFECTIONS IN ACUTE MYELOID LEUKEMIA IN THE POSACONAZOLE ERA

Abstract

Background:Posaconazole prophylaxis in patients with acute myeloid leukaemia (AML) changed the paradigm of fungal infections (FI).Aims:Description of FI and analysis of factors that might predispose to this type of infection in non‐allotransplant AML patients in the posaconazole era.Methods:Retrospective analysis of 144 consecutive non‐M3 AML patients diagnosed between January 2012 and June 2018 in a tertiary center and treated with intensive chemotherapy regimens with posaconazole prophylaxis, including autologous transplantation when performed in these patients. Multivariate regression analysis was performed to identify characteristics related to FI.Results:Median age at diagnosis was 52 years [19;71], 52% were females and 90% had an age‐adjusted Charlson score ≤3. Genetic risk group according to the European Leukemia Net 2017 classification was favourable in 28%, intermediate in 41% and adverse in 22%. Fourteen percent of patients (n = 20) had secondary AML. Patients were included since diagnosis and if completed remission‐induction intensive therapy up to transplant referral, the latter which occurred in 52% of patients (n = 75), with a median follow‐up of 7 months [1;81]. Only 7 patients had 1 episode of prophylaxis interruption, 3 due to mucositis and 4 out of our protocol. Median time of neutropenia per cycle was 26 days [5;180] and 10% of patients had >2 episodes of prolonged neutropenia (defined as ≥28 consecutive days of <500 neutrophils/microliter).Fungal infections were identified in 25 patients (17.4%) and classified according to EORTC criteria, with 5 proven, 13 probable and 7 possible infections. In 32% of patients FI occurred during remission‐induction (n = 8) of which 3 were diagnosed in the first week of neutropenia, 20% during consolidation treatment in first remission and 48% during relapse treatment. Of the confirmed infections, 3 were aspergillosis and 2 candidemia. Probable infections had pulmonary origin with no microbiology isolate or serologic positivity but identified by typical radiologic evidence; of these, broncho‐alveolar lavage and/or pulmonary biopsy was performed in 4 patients (31%) with negative results. For possible infections, antifungal therapy was initiated in a pre‐emptive manner for high risk patients with persistent fever despite large spectrum antibiotics.In a multivariate analysis, patients with FI had a higher odds of having relapsed AML and >2 episodes of prolonged neutropenia during treatment (p = 0.049 and p = 0.011, respectively). There was no mortality related to FI in this cohort of patients.Summary/Conclusion:Despite posaconazole prophylaxis, FI is still prevalent in AML patients. Infection during salvage treatment for relapsed disease and >2 previous periods of neutropenia exceeding 4 weeks should raise awareness for an increased risk of FI.