A randomised control trial to determine the efficacy of antibiotic prophylaxis during intensive phase of chemotherapy in children with Acute lymphoblastic leukaemia.

The treatment of acute lymphoblastic leukemia (ALL) has evolved significantly in the recent years. The overall and 5-year survival rates for children with ALL approach  90 percent. This is due to better understanding of genetics and  biological features of leukemic cells, resulting in  better risk stratification of children and optimization of treatment regimens through national and international collaboration.

 However, despite these high cure rates, the main problem is the treatment related mortality (TRM), which is estimated to be 4% in the developed countries . TRM is much higher in Low middle income countries (LMIC’s), ranging from 11 to 25 percent. Among these deaths, the most frequent causes are febrile neutropenia and infections mainly bacterial, which occur more frequently during intensive chemotherapy phase, such as induction. These infections not only directly lead to deaths, but can also cause delay in chemotherapy treatment, which can, in turn, lead to increase in relapses.

 Treatment related mortality contributes to a decrease in survival in LMIC’s . Infection rates are high in LMIC’s attributable to a large number of factors which include poor hygiene, overcrowding , undernutrition , poor access to urgent care and environmental factors such as poor sanitation , heat and humidity. Therefore, to reduce the risks related to infections in these patients, use of systemic antimicrobial prophylaxis can be possible approach.

 There is literature that shows the use of antibiotic prophylaxis in adult patients during intensive chemotherapy to reduce bacteremia and improve outcomes. In 2016, National Comprehensive Cancer network (NCCN) had recommended fluroquinolones (FQs) prophylaxis for adult patients with hematological malignancies.

 The use of antibiotic prophylaxis is still controversial in pediatric patients due to lack of data on effectiveness and best choice of antibiotic. However, there are few studies that have shown that prophylactic use of levofloxacin in patients with hematological malignancies has resulted in significant decrease in bacteremia. But the use of antibiotic prophylaxis is also associated with an increase in risk of FQs - resistant Gram negative bacteria development, invasive fungal infections (IFD), Clostridioides difficle (C.diffcile) infections and musculoskeletal toxicities. Thus, both the 8th European Conference on Infections in Leukemia (ECIL-8) and the Children’s Oncology Group do not currently support routine antibiotic prophylaxis in pediatric patients with acute leukemia.

More randomized prospective studies are required in pediatric patients to demonstrate the benefits of using antibiotic prophylaxis and to monitor for the emergence of resistant bacterias, C.difficle infections and IFD. With this background, this study aims to assess the efficacy and risk of levofloxacin prophylaxis in children with ALL receiving intensive chemotherapy.