Pediatric Febrile Neutropenia Guidelines in Asia Pacific: Development Process and Draft Recommendations

Background

Febrile neutropenia (FN) is one of the leading causes of morbidity for pediatric patients receiving chemotherapy. Standardized approaches, including clinical practice guidelines (CPGs) may improve patient outcomes. Most recommendations have originated from high-income settings, limiting their applicability in developing countries. A network of healthcare professionals across the Asia-Pacific region was thus convened to collaborate on a guideline for management of pediatric patients with febrile neutropenia.

Methods

A steering committee of content experts and methodologists spearheaded the initiative. Stakeholder surveys identified 25 priority topics, which were refined into key clinical questions with guidance from an expert team from the St Jude Global Alliance. A systematic review of the evidence was conducted using Rayyan software, with dual-blinded study selection and risk-of-bias assessment. Data were synthesized and outcomes were presented in Summary of Findings Tables using GRADEpro; the methodology of GRADEpro was adapted with inputs from methodologists from the University of Florida. A multidisciplinary CPG development panel, including patient and family representatives from Asia-Pacific countries, was trained in evidence evaluation and guideline development. Recommendations were finalized through an in-person consensus meeting with the provision of voting on recommendations.

Results

A total of 26 questions were reviewed. In common with most guidelines, a number of questions focused on diagnostics (questions 3-7), choice of initial antimicrobial therapy in low risk versus high risk FN (questions 8-13), modifications to antimicrobial therapy bases on culture reports and duration of FN (questions 14-16), and discontinuation of therapy during the afebrile period (questions 24-26). Review of the literature showed limited evidence for several of the questions raised, but overall the panel recommendations were consistent with existing guidelines considering the challenges existing in resource limited settings.

Recognizing the prevalence of diseases such as tuberculosis (TB) and vector borne infections in the region, evidence to support testing for these conditions in the context of febrile neutropenia was also examined. The panel suggested testing for TB in all patients presenting with febrile neutropenia who are exposed and/or have clinical features suggestive of TB. The panel also suggested routinely testing for endemic diseases (such as malaria, leishmaniasis, schistosomiasis, dengue, chikungunya) when applicable.

Conclusions

The development of these CPGs not only provided evidence-based recommendations tailored to the Asia-Pacific region but also strengthened local expertise in guideline creation. By addressing diseases of regional significance, these guidelines enhance the relevance and effectiveness of FN management, bridging gaps between global standards and local healthcare needs.