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Background: Central line-associated bloodstream infections (CLABSIs) are critical infectious complications among pediatric hematology-oncology patients, and the management of central venous catheters (CVCs) by healthcare personnel can significantly influence the incidence of these infections. This study evaluates the impact of nurse-led changes in CVC management on the incidence of CLABSIs., Methods: This single-center, retrospective observational study was conducted at an urban, tertiary referral, and academic center serving pediatric patients., Results: The study cohort comprised 239 patients and 323 CVCs seen between 2012 and 2022. CLABSI was defined according to the Centers for Disease Control and Prevention definitions. Oncology nurse leaders developed CVC-specific educational modules for CLABSI prevention. All the relevant information during the CVC maintenance period was noted in the patient's CVC logbook. A total of 24 (7%) cases of confirmed CLABSI were identified. The incidence of CVC-related infections was 0.32 cases per 1000 catheter days (95%CI: 0.19-0.45). The incidence decreased by 40% between the first and second three-year study period. Documented exit-site infection was reported in 32 (10%) cases. The correlation between exit-site infection and CLABSI was found in 9 (28%) cases. Our CVC-related infection rates are significantly lower than the incidence reported by the Italian Association of Pediatric Hematology and Oncology, which settles at 3-5 cases per 1000 catheter days., Conclusions: Our data confirm the effectiveness of local CVC management guidelines in preventing CVC-related infectious complications.