Common SAEs and their impact on the prognosis of children treated with the CCCG-ALL-2015 protocol: a retrospective multicentre Chinese study

This study was intended to evaluate common serious adverse events (SAEs) and analyze their effects on the prognosis of acute lymphoblastic leukemia (ALL) children. We retrospectively collected the data of 7640 consecutive ALL children with/ without SAEs who were enrolled in CCCG-ALL-2015 protocol in 20 centers between 2015 and 2021. The epidemiological, clinical and outcome data were collected based on the designed case report form (CRF). Multivariable logistic regression analysis was used to assess the association between baseline clinical characteristics and SAEs. Time-dependent Cox regression analysis evaluated the association between SAEs and subsequent overall survival (OS). Multivariable Cox analysis was applied to evaluate the impact of parameters on OS in patients with SAEs. Of 7640 children, there were 842 (11.0%) suffered from a total of 1013 cases of SAEs in CCCG-ALL-2015 protocol and the commonest SAEs were infection-related SAEs 669/1013, 66.0%). SAEs mostly (46.2%) occurred during the induction phase, followed by the stage 1 of continuation phase (23.6%) and the stage 2 of continuation phase 17.1%), commonest SAEs during these three phases were severe pneumonia (30.8%, 39.0% and 62.4% of the whole SAEs during each phase, respectively). Multivariable logistic regression models showed that age at diagnosis < 1 year, T-ALL, intermediate risk (IR)/high risk (HR) groups, CNS3 and traumatic lumbar puncture (TLP+) were independently associated with an increased risk of developing SAEs. Time-dependent Cox regression analysis indicated that SAEs were associated with subsequent poor OS. Multivariable cox regression analysis identified adverse prognostic effects of factors such as active abandonment and infection in patients with SAEs. SAEs occurred during the chemotherapy in CCCG-ALL-2015 protocol influenced the prognosis for ALL children. Focal prevention and cure for specific SAEs could be adapted to further improve the chemotherapy completion rate and outcome in China.