Avaliação do uso de profilaxia antifúngica e perfil clínico de pacientes acometidos por leucemia mieloide aguda

Abstract

Introduction: Acute leukemias are complex diseases to treat and have a high mortality rate. Immunosuppression resulting from chemotherapy makes the patient susceptible to a variety of infections, including invasive fungal infections (IFIs). Infections are among the leading causes of death in patients undergoing chemotherapy for the treatment of acute myeloid leukemia. Induction chemotherapy, the first initiative in treatment, stands out as being effective in achieving remission, but high toxicity results in a high mortality rate, partly resulting from bacterial, viral, and fungal infections. The use of antifungal and antibacterial drugs as prophylactics has been shown to be effective in preventing these infections, but their use is still optional. Because of this, only a few treatment centers have established antifungal prophylaxis protocols. Therefore, this work aimed to carry out a systematic review and meta-analysis regarding the use of antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and to investigate the frequency of fungal and bacterial infections in patients with acute myeloid leukemia who underwent induction chemotherapy at the Cancer Hospital of Uberlândia between 2017 and 2021, evaluating whether the prophylaxis used reduced the number of infections. Methodology: The systematic review was performed using a population-variable-outcome (PVO) strategy, with chosen keywords used for online database searches. Included studies were selected and data collected to develop descriptive results for all studies and, for studies that fit the criteria, a relative risk (RR) meta-analysis was performed for frequency of infections, in-hospital mortality, and complete remission (CR). After carrying out the systematic review and meta-analysis, a retrospective study was carried out at the Cancer Hospital of Uberlândia, which began by formulating a list of medical records of patients who were identified with the international classification of disease code referring to acute myeloid leukemia. From this list, the data present in the Hospital Information System (SIH) and in physical records in the statistics sector of the Clinical Hospital of the Federal University of Uberlândia (HC-UFU) were analyzed. The collected data were then organized and analyzed to identify frequency of infections, effect of prophylaxis, survival, and use of antibiotics in these patients. Results: A total of 33 studies were included in the systematic review, most of which showed positive results (n=28/33) regarding the use of antifungal prophylaxis. Using a random-effects model, pooled results from the meta-analysis showed lower frequencies of invasive fungal infections in AML patients when antifungal prophylaxis was used, and the use of prophylaxis did not affect remission rates. Among the antifungals used, posaconazole stood out as one of the best agents to be used for prophylaxis. As for the retrospective study, 85 participants were included, with a similar proportion between men and women, with an average age of 54 years. The risk of mortality increased with age, with participants under 50 years of age having the lowest death rate and, additionally, it was found that intermediate-risk leukemia also had the lowest risk of death. The main antifungal prophylactic used was fluconazole, representing 56.1% of the cases, while the main antibacterial prophylactic was levofloxacin representing 34.1% of the participants. Aspergillosis was the main fungal infection (64.7%), treated mainly with voriconazole. Prophylaxis did not result in a decrease in the number of proven cases of fungal infection, but it did reduce the number of suspected cases. Antibacterial prophylaxis also did not result in a significant difference in the number of cases of bacterial infections. Fungal and bacterial infections in participants had a significant impact, reducing overall survival. Therefore, although the prophylactic use of fluconazole has been shown to be effective in reducing the number of suspected cases of infection, no significant impact was observed in the reduction of confirmed cases. Furthermore, infections were found to have a negative impact on overall patient survival, highlighting the need to investigate new prophylactic approaches for this specific group of patients. Conclusions: Antifungal prophylaxis is a useful tool with high potential in patients with acute myeloid leukemia undergoing induction chemotherapy. The systematic review and meta-analysis showed consistent results that support the use of pharmacological prophylaxis, especially posaconazole. However, the individual conditions of each treatment center and region must be considered when choosing the most appropriate medication. In the retrospective study, a significant proportion of aspergillosis cases were observed, and both fungal infections and bacterial infections had a negative impact on participants' survival. However, the retrospective study also revealed the ineffectiveness of fluconazole as a prophylactic measure, which raises concerns about its specific use as a prophylactic agent against fungal infections.