Akut Lösemi Hastalarında İnvaziv Fungal Enfeksiyonlar

Abstract

In this study, we aimed to determine the distribution of invasive fungal infections (IFI), risk factors and agent spectrum, to evaluate them according to the EORTC/MSG criteria, to investigate the efficiency of bronchoalveolar lavage (BAL) as a diagnostic method and to perform survival analysis in adult acute leukemia patients. The incidence of IFI was found to be 33.1% in 502 patients who were followed up in an inpatient ward or intensive care unit between 2003 and 2020. While there was no difference in the risk of developing IFI according to the type of acute leukemia, the incidence was shown as 33% in patients with AML or ALL. Lung involvement was found to be the most (93.4%), however it affected neither survival time nor death risk. The most common clinical symptom in patients with IFI was fever (79.5%), the most common thoracic CT finding was macronodules (77.7%) and the most common agent was Aspergillus. According to the definition criteria established by EORTC/MSG to avoid delays in diagnosis, 32 (19.3%) patients were defined as proven IFI, 35 (21.1%) patients as probable IFI, and 99 (59.6%) patients as possible IFI. When only proven and probable IFI were evaluated, the incidence of IFI was determined as 13.3%. All patients included in the study had the host factor required by EORTC/MSG, due to their haematological malignancies, when additional clinical and mycological criteria were required for the diagnosis of proven or possible IFI. Aspergillus galactomannan (GM) antigen test has been found positive in serum in 39 (23.5%) patients and in BAL fluid in 6 (3.6%) patients. Fungal elements have been demonstrated or pathogens been produced in 13 (7.8%) sputum cultures and 4 (2.4%) BAL fluid cultures. BAL was applied to a total of 26 patients with IFI, and contributed to proven or probable IFI diagnosis in 10 patients. Hereunder, BAL efficiency was determined as 38.4% in our study. The risk of developing IFI was increased 3.5 times in 136 (81.9%) patients with neutropenia (95% confidence interval (CI): 2.248, 5.531), 2.5 times in 64 (38.6%) patients who were followed up in the intensive care unit (95% CI: 1.669, 3.801) and 1.8 times (95% CI: 1.195, 2.997) in 42 (25.3%) patients who underwent mechanical ventilator (MV). Although the main pathogen isolated from proven IFI cases was Aspergillus (14, 43.8%), Candida (9, 28.1%), Mucor (8, 25.0%) and PCP (1, 3.1%) were also detected. Our study was not aimed to detect antifungal efficacy or safety, however it was observed that almost all patients were given antifungal prophylaxis, and adapted to empirical, preemptive or targeted antifungal therapy according to the follow-up. Voriconazole (24.1%) was used the most as an antifungal agent. The mean survival time of patients with IFI was determined as 5 (1.9-8) months. While the mean survival time of patients without intensive care follow-up was 13 months, it was 1 month in patients with intensive care follow-up, and also a 2.49-fold increase in death risk was found. Similarly, while the mean survival time of patients who did not receive MV was 62 months, it was 4.4 months in patients who were administered MV, and also a 3.82-fold increase in death risk was found. The mean survival time of Mucor infection (1 month) was found to be statistically significantly lower than other pathogens. There was no significant difference in IFI diagnosis or survival time between patients who were applied BAL or not. As of the termination date of the study, IFI-related deaths were detected in 116 (69.9%) of 166 patients with IFI. According to the results, IFI is an important cause of morbidity and mortality in acute leukemia patients. Lung involvement is seen the most and lung samples such as sputum or BAL fluid can contribute to the diagnosis. Also neutropenia, intensive care follow-up and MV administration are associated with an increased risk in the development of IFI and of death, and mold agents are gradually increasing in patients with haematological malignancies, considering the previous studies. Finally, as a center that provides diagnosis and treatment of patients with haematological malignancies, we recommend in the IFI approach in patients with acute leukemia, to be aware of IFI in patients receiving intensive chemotherapy and/or recipients of haematopoietic stem cell transplantation, and to evaluate with microbiological, serological and radiological tests during the clinical follow-up, and if necessary, to apply invasive diagnostic methods such as bronchoscopy or tissue biopsy.