Ps1281 Efficacy of Active Surveillance in Reducing Mortality Due to Multidrug Resistant Bacteria in Acute Leukemia

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.