141 - Efficacy of fluoroquinolone prophylaxis during induction phase in children with acute lymphoblastic leukemia: a systematic review and meta-analysis

Publication Number: 2135.141

Maria C.. Landivar, Universidad San Francisco de Quito, Quito, Pichincha, Ecuador; Isabela Hartmann Rost, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil; Ana Carvalho Kilson, Nossa Senhora de Lourdes Hospital Foundation, Belo Horizonte, Minas Gerais, Brazil; Maria A.. Torres, Universidad Tecnológica de Pereira, Cali, Valle del Cauca, Colombia; Ana G. Santarosa Vieira, Private Practice, São Paulo, Sao Paulo, Brazil

Background: Infections during acute lymphoblastic leukemia (ALL) induction chemotherapy are a leading cause of treatment-related mortality. The role of infection prevention with fluoroquinolone prophylaxis, specifically during this phase in pediatric ALL, remains unclear. Therefore, we conducted a systematic review and meta-analysis to assess its efficacy.

Objective: To evaluate whether fluoroquinolone prophylaxis during induction chemotherapy in children with ALL reduces the risk of infections and consequently mortality.

Design/Methods: PubMed, Scopus and Cochrane databases were systematically searched for randomized controlled trials (RCTs) and observational studies. Main outcomes were febrile neutropenia, bloodstream infection, Clostridioides difficile infection (CDI) and all-cause mortality among pediatric ALL patients using fluoroquinolone prophylaxis compared to no prophylaxis during induction chemotherapy. Heterogeneity was assessed with I² statistics and a random-effect model was used for outcomes with high heterogeneity. This review follows PRISMA guidelines and was prospectively registered on PROSPERO (CRD: CRD420251175361).

Results: We included 7 studies with 991 patients, of whom 439 (44.3%) used fluoroquinolone prophylaxis. Levofloxacin and ciprofloxacin were used in the included studies, with 255 and 184 patients respectively. The B-cell immunophenotype was the most frequent subtype in every study included. Fluoroquinolone prophylaxis reduced the risk of febrile neutropenia when compared with children without prophylaxis (46.1% vs 64.9%; OR 0.44; 95% CI 0.33-0.59; p = 0.002; I² = 0%; Figure 1). A subgroup analysis including only studies that used levofloxacin (OR 0.46; 95% CI 0.33-0.64; p = 0.005; I² = 0%) showed consistent results with the overall analysis, indicating no significant difference with ciprofloxacin. Fluoroquinolone prophylaxis also significantly reduced the risk of bloodstream infection (9.3% vs 14.4%; OR 0.50; 95% CI 0.32-0.81; p = 0.019; I² = 0%; Figure 2). Risk of CDI (2.4% vs 9.9%; OR 0.43; 95% CI 0.00-42.30; p = 0.508; I² = 39.6%; Figure 3) and all-cause mortality (7.8% vs 6.9%; OR 1.04; 95% CI 0.20-5.38; p = 0.948; I² = 54.3%) were not significantly different between groups and a moderate heterogeneity was observed.

Conclusion(s): Fluoroquinolone prophylaxis during induction chemotherapy in pediatric ALL significantly reduces febrile neutropenia and bloodstream infections without increasing C. difficile risk. Although over-all mortality remained unchanged, reducing infectious morbidity may enhance treatment tolerance. Larger randomized trials are needed to evaluate long-term safety.

FIGURE 1 Febrile neutropenia developed in pediatric patients with ALL during induction chemotherapy receiving fluoroquinolone prophylaxis versus those receiving no prophylaxis.
Each square represents an individual study, with the size proportional to its weight in this review. Horizontal lines indicate 95% confidence intervals. The diamond represents the pooled estimate. An odds ratio below 1 means favors fluoroquinolone prophylaxis group.
OR, odds ratio; CI, confidence interval.

FIGURE 2 Bloodstream infection developed in fluoroquinolone prophylaxis versus no prophylaxis pediatric patients with ALL during induction chemotherapy.
Formatting and symbols are as in Figure 1.
OR, odds ratio; CI, confidence interval.

FIGURE 3 CDI developed in pediatric patients with ALL receiving or not fluoroquinolone prophylaxis during induction chemotherapy.
Formatting and symbols are as in Figure 1.
OR, odds ratio; CI, confidence interval.