Retrospective evaluation of the USE of primary antifungal prophylaxy in children with leukemia

The initial and most intense chemotherapy period of acute leukemia treatment is the induction period. During the induction chemotherapy period, many factors, especially neutropenia, increase the risk of developing invasive fungal infections (IFI) in leukemia patients. Initiation of antifungal prophylaxis in leukemia patients reduces the risk of invasive fungal infections and has a positive effect on treatment continuation and mortality. Antifungal prophylaxis is started for every patient diagnosed with acute leukemia at Dokuz Eylül University Hospital. Different antifungal prophylaxis agents were used in different periods for the patients. In this study, demographic characteristics of patients, risk factors for IFI and characteristics of IFI cases seen in our clinic were defined. It was aimed to compare the antifungal prophylaxis agents used in our study in terms of empirical antifungal treatment use, development of IFI, development of side effects and primary antifungal prophylaxis success. It is aimed that the findings obtained from our study will guide our primary antifungal prophylaxis strategy in the next period. Patients under the age of 18 who were diagnosed with acute leukemia in Dokuz Eylul University Hospital Pediatric Hematology Clinic between January 2010 and January 2022 and given primary antifungal prophylaxis with induction chemotherapy were included in the study. The study was conducted on 195 patients. Patient data were scanned from the Dokuz Eylul University Hospital system, along with the files within the department. It was determined that 10.8% of the patients were diagnosed with T cell ALL, 74.4% with B cell ALL and 14.9% with AML. It was determined that 26.7% of the patients were in the standard risk group, 41.5% in the medium risk group and 31.8% in the high risk group. During the induction chemotherapy period, fluconazole was administered to 63.1%, caspofungin to 2.6%, L-AmB to 27.2%, micafungin to 3.6%, posaconazole to 3.1%, and 0.5% received voriconazole. It was determined that 34.4% of the patients were given empirical antifungal treatment, and the most commonly used empirical antifungal agent is caspofungin, followed by L-AmB. In our study, the antifungal prophylaxis failure rate was determined as 48.7%, and the most common reason for antifungal prophylaxis failure was initiation of empirical antifungal therapy. It has been demonstrated that patients with AML receive more empirical antifungal therapy than patients with ALL. Empirical antifungal therapy was needed in 19.2% of the patients in the standard risk group, 33.3% of the patients in the intermediate risk group, and 48.3% of the patients in the high-risk group. Proportionally, the highest incidence of IFI was seen in AML patients, and no statistically significant difference could be obtained between patients. The success of antifungal prophylaxis was statistically significantly lower in patients with AML than in patients with ALL. Likewise, being included in the leukemia high risk group increased the risk of prophylaxis failure. Prolonged neutropenia was another factor that increased the failure of antifungal prophylaxis. Antifungal prophylaxis agents were compared in the parameters of IFI, prophylaxis failure and empirical antifungal treatment, and no statistically significant difference was found between them. Micafungin and fluconazole were the agents that stopped the most antifungal prophylaxis due to side effects, and LFT elevation was observed in all of them. The overall incidence of IFI among patients included in the study was 1.82 per 1000 antifungal prophylaxis. In our study, the incidence of IFI in the fluconazole group, which is one of the two most commonly used agents, was 1.99 per 1000 prophylaxis days. The IFI rate remained at 1.13 in the group using L-AmB. The diagnosis of all patients with invasive fungal infection was invasive aspergillosis. Mortality did not develop in any of our patients diagnosed with invasive fungal infection. In our study, the main invasive fungal infection detected during the induction chemotherapy period was invasive aspergillosis. Therefore, it is appropriate to start antifungal prophylaxis with mold effect during the induction chemotherapy period.