Incidence and predisposing factors of infection in patients treated with hypomethylating agents.

OBJECTIVE: Hypomethylating agents may have adverse effects such as cytopenias, cytopenia associated infections and fatality due to infections despite their favorable effects in the treatment of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The infection prophylaxis approach is based on expert opinions and real-life experiences. Hence, we aimed to reveal the frequence of infections, predisposing factors of infection and to analyse infection attributable mortality in patients with high-risk MDS, CMML and AML who received hypomethylating agents in our center where routine infection prophylaxis is not applied. MATERIAL-METHOD: 43 adult patients with AML or high-risk MDS or CMML who received HMA ≥ 2 consecutive cycles from January 2014 to December 2020 were enrolled in the study. RESULTS: 43 patients and 173 treatment cycles were analyzed. The median age was 72 years and 61.3 % of patients were males. The distribution of the patients' diagnoses was; AML in 15 patients (34.9 %), high risk MDS in 20 patients (46.5 %), AML with myelodysplasia-related changes in 5 patients (11.6 %) and CMML in 3 patients (7 %). 38 infection events (21.9 %) occurred in 173 treatment cycles. 86.9 % (33 cycles) and 2.6 % (1 cycle) of infected cycles were bacterial and viral infections, respectively and 10.5 % (4 cycles) were bacterial and fungal concurrently. The most common origin of the infection was respiratory system. Hemoglobin count was lower and CRP level was higher at the beginning of the infected cycles significantly (p values were 0.002 and 0.012, respectively). Requirement of red blood cell and platelet transfusions were found to be significantly increased in the infected cycles (p values were 0.000 and 0.001, respectively). While > 4 cycles of treatment and increased platelet count were found to be protective against infection, > 6 points of Charlson Comorbidity Index (CCI) were found to increase the risk of infection. The median survival was 7.8 months in non-infected cycles while 6.83 months in infected cycles. This difference was not statistically significant (p value was 0.077). DISCUSSION: The prevention and management of infections and infection-related deaths in patients treated with HMAs is crucial. Therefore, patients with a lower platelet count or a CCI score of > 6 may be candidates for infection prophylaxis when exposed to HMAs.

The evaluation of risk factors leading to early deaths in patients with acute promyelocytic leukemia: a retrospective study.

Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients.

Vancomycin-resistant enterococci infection and predisposing factors for infection and mortality in patients with acute leukaemia and febrile neutropenia.

BACKGROUND: Vancomycin-resistant enterococcus (VRE) is an infectious agent that can increase morbidity and mortality, especially in patients with neutropenia in haematology departments. We analysed VRE infections and mortality rates among VRE colonized patients with acute leukaemia, defined predisposing risk factors for infection and mortality, and investigated the influence of daptomycin or linezolid treatment on mortality. PATIENTS-METHODS: We included 200 VRE colonized adult acute leukaemia patients with febrile neutropenia between January 2010 and January 2016. Data were collected from electronic files. RESULTS: There were 179 patients in the colonized group, and 21 patients in the infected group. Enterococcus faecium (van A) was isolated from all patients. The infection rate was 10.5 %, and the types of infections noted were as follows: bloodstream (n = 14; 66.7 %), skin and soft tissue (n = 3; 14.3 %), urinary (n = 2; 9.5 %), and others (9.5 %). In the multivariate logistic regression analysis, exposure to invasive procedures, coinfection status, and >15 days of VRE positivity were independent risk factors for VRE infections. In hospital mortality rates were 57.1 % in the infected group, and 9.5 % in the colonized group (p < 0.001). Older age, female gender, absolute neutropenia, and coinfection status were statistically significant predictor of survival. CONCLUSION: Vancomycin-resistant enterococcus infections are associated with high morbidity and mortality in haematology patients with neutropenia. Clinicians should be aware of predisposing risk factors for VRE infection to avoid unfavourable outcomes. We believe that larger studies are necessary regarding the influence of treatment with daptomycin and linezolid.