Retrospective Analysis of Incidence and Etiology of Severe Infections in Children Receiving Therapy for High‐Risk Neuroblastoma: A Large Single‐Center Experience

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BACKGROUND: Severe infections are a leading cause of morbidity and mortality in pediatric oncology, especially among children receiving high-dose chemotherapy. High-risk neuroblastoma (HR-NB) provides a paradigmatic model of prolonged multimodal treatment, yet recent data describing the burden and timing of severe infections during its therapeutic course are limited. PROCEDURE: We retrospectively reviewed 184 consecutive HR-NB patients diagnosed and treated at the IRCCS Istituto Giannina Gaslini (Genoa, Italy) according to the SIOPEN/HR-NBL1 protocol between 2002 and 2021. Severe infectious events were defined as bloodstream infections (BSI) and invasive fungal diseases (IFDs) according to international criteria. Incidence rates per 100 patient-days at risk (pdr) and phase-specific distributions (induction, consolidation, maintenance) were analyzed. RESULTS: Over 80,202 patient-days at risk, 104 severe infections were recorded (cumulative incidence 56.5%). BSI represented 93.3% of events, predominantly Gram-positive (55.8%) and Gram-negative (37.5%) pathogens; 6.7% were IFDs. The induction phase accounted for the highest incidence, while consolidation (hematopoietic stem cell transplantation) showed the highest infection rate per pdr. Approximately 70% of BSI occurred in non-neutropenic patients and were central venous catheter (CVC) related; in neutropenic cases (30%), half were CVC associated. Infection-related mortality was 1.1% (two out of 184). CONCLUSIONS: Severe infections remain frequent and clinically significant complications in HR-NB therapy, though infection-related mortality was low. The low incidence of IFDs despite the absence of systematic prophylaxis suggests potential optimization of preventive strategies. These data provide an epidemiologic benchmark for infection risk in the era of immunotherapy and CAR-T approaches for solid tumors.

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