Infectious Complications During Early Treatment of Childhood Acute Lymphoblastic Leukemia-A Comparison Between the ALLTogether and NOPHO ALL-2008 Protocols.

Introduction: Infection remains the most common treatment-related toxicity of childhood ALL, emphasizing the need to identify patients at risk and to tailor treatment strategies accordingly.

Aims: The primary aim was to compare infectious toxicity during early treatment for childhood ALL following the ALLTogether and NOPHO ALL-2008 (ALL-2008) protocols, and second, to identify risk factors for infectious toxicity.

Methods: A national retrospective matched cohort study was conducted, including 345 patients aged 1-17 years diagnosed with ALL and treated in Sweden according to the ALLTogether or ALL-2008 protocols. Nonparametric tests were used to compare infectious outcomes between protocols, and regression modeling was used to identify risk factors of the infectious outcomes.

Results: Treatment following ALL-2008 showed higher infectious toxicity during induction, whereas treatment following ALLTogether showed increased infectious toxicity during consolidation 1. Overall, treatment according to ALL-2008 was associated with a higher incidence of infections. Anthracycline use and young age (1-9 years) were associated with both higher infectious incidence and more severe infectious complications. Dexamethasone was associated with both lower incidence and lower severity of infectious complications as compared to prednisone.

Conclusions: A notable shift in the timing of infectious toxicity was observed between the two treatment protocols. Risk factors for infectious toxicity during early treatment include anthracycline use and young age. Dexamethasone as an induction steroid was associated with lower infectious burden, although its effect is difficult to isolate from the simultaneous anthracycline effect. The findings suggest that treatment composition plays a central role in determining both the extent and timing of infectious complications.