Findings of infection in children with acute leukemia

Acute leukemia is the most common malignancy of childhood, overall survival rates has increased to 90% for acute lymphoblastic leukemia (ALL) and 60% for acute myeloblastic leukemia (AML). But, infections are still an important cause of morbidity and mortality in this patients. In this study, 291 children; 242 with ALL and 49 with AML (123 female/168 male, mean age 6,11±4,79 years (1-17 years 9 months)), diagnosed with acute leukemia between the ages of 1-18 years, in Hacettepe University, İhsan Doğramacı Children's Hospital, Department of Pediatric Hematology between January 1, 2008 and December 31, 2019 were retrospectively reviewed and infection episodes recorded during induction, consolidation and reinduction treatments were evaluated. Patients with infections during relapse or hematopoietic stem cell transplantation periods and patients with underlying diseases that would cause more frequent infections were not included. Of the ALL patients, 181 were treated with the St. Jude Total XV protocol, 61 of them were treated with the BFM ALL-IC 2009 protocol, and infectious complications of these two groups were compared. Fever was observed as a complaint in 40.5% of the patients at the time of diagnosis. Total of 575 infection episodes, 402 in the St. Jude Total XV group and 173 in the the BFM ALL-IC 2009 group were observed, total number of infection episodes was similar between the two groups (p=0.261). At least one microbiologically documented episode of infection was observed in 53% of the St. Jude Total XV group and 62.3% of BFM ALL-IC 2009 group. In patients with ALL, 38.4% of the 575 infection episodes were microbiologically documented, 27.3% were clinically documented infections, and 34.3% were fever of unknown origin (FUO). The number of microbiologically documented infections was higher in BFM ALL-IC 2009 group than the St. Jude Total XV group (p=0.004). The mean of episodes with prolonged neutropenia found in the BFM ALL-IC 2009 group was found to be significantly higher than the St. Jude Total XV group (p<0.001). Neutropenia was present during the diagnosis of infection in 76.9% of the infection episodes of the St. Jude Total XV group and in 72.8% of the infection episodes in the BFM ALL-IC 2009 group. In ALL patients, absolute neutrophil count (ANS) ≤ 100 / mm3 during the infection episode (OR 41.53; 95% CI 4.51-382.02; p=0.001), ANS during the infection episode as 100-500 / mm3 (OR 74.03; 95% CI 6.87-797.78; p<0.001) and presence of a central venous catheter (CVC)/port in the patient (OR 176.46; 95% CI 16.79-1853.99; p <0.001) was associated with an increased risk of infection. Of the total 575 episodes of infection in ALL patients, 77.4% were febrile neutropenia, 21.9% were CVC/port-related infection, 12.9% were viral infection, 5.9% were fungal infections. In ALL patients; receiving BFM ALL-IC 2009 protocol (OR 4.75; 95% CI 2.10-10.73; p <0.001), hospitalization during febrile neutropenia attack (OR 2.02; 95% CI 1.40 -2.93; p<0.001) and prolonged neutropenia (OR 3.95; 95% CI 2.45-6.38; p <0.001) were found to be associated with an increase in the risk of febrile neutropenia. The frequency of fungal infections in ALL patients is 5.9% (23.5% proven, 76.5% possible invasive fungal infection). Prolonged neutropenia (OR 2.01 95% CI 1.15-3.50; p=0.014); prolonged fever (OR 2.12; 95% CI 1.31-3.43; p=0.002); being younger than 3.5 years in ALL patients (OR 0.87; 95% CI 0.56-0.77; p=0.006; AUC 0.068; sensitivity 72%; specificity 62.2%) were found to be factors increasing the frequency of fungal infections. Mean values of febrile neutropenia, CVC/port-associated infections and viral infections in the BFM ALL-IC 2009 group were higher than St. Jude Total XV group, number of fungal infections was higher in the St. Jude Total XV group. However, this difference was found to be significant only in terms of viral infection (p=<0.001). The infection sites among ALL patients were; skin infection/concomitant oral mucositis (15.8%), pneumonia (12.2%), gastrointestinal system infection (11.7%), upper respiratory tract infection (URTI) (6.4%), urinary system infection (2.8%). Skin infection/concomitant oral mucositis, gastrointestinal tract infection, urinary tract infection and URTI count were found to be significantly higher than the St. Jude Total XV group (p values, respectively; <0.001; <0.001; 0.028; 0.020). In ALL study group 4/242 (1.7%) of the patients died due to infection, these four patients were in the St. Jude Total XV group. In a total of 206 infection episodes in the 49 AML patients at least one microbiological agent was shown in 45.1%, 27.2% was classified as clinically documented infection and 27.7% as FUO. Infection attacks in patients with AML, 82% were febrile neutropenia, 27.2% were CVC / port-related infection, 17.5% were viral infection, and 15% were fungal infection. Hospitalization during the febrile neutropenia (OR 3.31; 95% CI 1.38-7.92; p=0.007), prolonged neutropenia (OR 3.47; 95% CI 1.17-10.24; p = 0.024)) in patients with AML were found to be factors associated with the increase in the frequency of febrile neutropenia. In patients with AML, 31 invasive fungal infection episodes (8 proven, 2 probable, 21 possible) were detected. In AML patients, pneumonia 36 (17.5%), skin infection- concomitant oral mucositis 36 (17.5%), gastrointestinal system infection 28 (13.6%), genitourinary system infection 7 (3.4%), URTI was observed in 9 (4.4%) episodes. Infection-related mortality rate in AML patients was found to be 6.1% (3/49). Incidence of death due to infection was found to be low in patients with ALL and AML. In ALL patients; neutropenia and presence of CVC/port in total infection frequency; being treated with the BFM ALL-IC 2009 protocol, hospitalization during febrile neutropenia, prolonged neutropenia in the frequency of febrile neutropenia; being younger than 3.5 years old, prolonged neutropenia and prolonged fever were associated with an increase in the frequency of fungal infections. Although our study is retrospective, it is an original study in terms of comparing the infection frequency of patients using St. Jude and BFM Protocols.