Infectious Complications in Children with ALL Treated with ALL-IC-2009 Protocol: Multicenter National Study of Polish Society of Pediatric Hematology and Oncology
Authors: Salamonowicz Malgorzata , Hutnik Lukasz , Matysiak Michal , Rogulska Joanna , Podsiadly Edyta , Demkow Urszula , Malas Zofia , Badowska Wanda , Zajac-Spychala Olga , Wachowiak Jacek , Pierlejewski Filip , Mlynarski Wojciech , Tomaszewska Renata , Szczepanski Tomasz , Ociepa Tomasz , Urasinski Tomasz , Czyzewski Krzysztof , Wysocki Mariusz , Urbanek-Dadela Agnieszka , Karolczyk Grazyna , Gamrot Zuzanna , Wieczorek Maria , Plonowski Marcin , Krawczuk-Rybak Maryna , Stolpa Weronika , Sobol-Milejska Grazyna , Irga-Jaworska Ninela , Drozynska Elzbieta , Chelmecka-Hanusiewicz Liliana , Balwierz Walentyna , Gorczynska Ewa , Kalwak Krzysztof , Kowalczyk Jerzy , Styczynski Jan 
Published: October 2019

Abstract
BACKGROUND. Infectious complications are a significant cause of morbidity and mortality in children receiving treatment for ALL. One of the major factors increasing the risk of bacteremia is the widespread use of central venous lines (CVL). In this study we hypothesized if there are any outcome predictors during bacteremia episodes during standard chemotherapy.
OBJECTIVE. The aim of the study was to analyze epidemiology and impact of bacteremia as a main cause of death during induction and consolidation therapy of ALL in children. We assessed an influence of following factors: age, sex, time to infection, duration of antibiotic treatment, and relapse on survival in ALL children with bacteremia.
METHODS. We reviewed 430 medical charts of children with ALL treated in Pediatric Hematological Centers in Poland according to ALL-IC-2009 protocol between January 2012 and December 2013. The group of 110 children (71 boys, 39 girls) with ALL with at least 1 episode of bacteremia was analyzed. The median age of the children was 7.5 years. Statistical analysis was performed using chi-squared and t-test when applicable to estimate the influence of different factors (age, sex, time to infection, period of treatment) for the outcome.
RESULTS. The overall incidence of bacteremia among ALL children was 110/430 (25.6%). The most common cause of bacteremia (20%) was S.epidermidis (22%) and E.Coli ESBL(+). The median time to infection (TTI) was 4.9 months . There was no significant association between TTI and outcome of the patients (p=0.07), but there was a trend towards increased death rate during consolidation therapy. The median duration of infection treatment (MDT) was 13.6 days. MDT did not influence significantly death rate (p=0.31). Among all patients, 14 (12.7%) deaths were observed. The median age of children in that group was 9.1 years. In the analyzed period 19 cases of ALL relapse were observed in this study. In the relapse group there was significantly higher mortality rate than in the group with “de novo ALL” (p<0.01). Mortality rate was significantly higher among boys (p<0.01). There was no correlation between age of children and incidence of deaths (p=0.14).
CONCLUSIONS. The incidence of bacteremia in children treated for ALL in Poland is 25.6%. Staphylococcus epidermidis and Escherichia Coli ESBL(+) are the mostcommon pathogens. Bacteria translocation from intestines to the blood might play a key role in development of blood-stream infection (BSI), thus the gut decontamination may be of high value in high-risk patients. Children with ALL relapse are at high risk of mortality due to bacteremia. Boys are more predisposed to life-threatening episodes and higher mortality due to BSI. Age is not a predictor factor for bacteremia related mortality. Children during consolidation chemotherapy of ALL require special attention to avoid bacteremia episodes.

Disclosures
No relevant conflicts of interest to declare.