Incidence and Risk Factors of Serious Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia: A CYP‐C Population‐Based Study

Background Osteonecrosis (ON) is a debilitating complication of acute lymphoblastic leukemia (ALL) therapy. While numerous studies have explored its incidence and associated risk factors, investigations using large‐scale cohorts remain important to characterize ON across heterogeneous populations. Objectives were to describe the incidence and risk factors of ON among Canadian pediatric patients with ALL. Method This nationwide retrospective cohort study included children <19 years diagnosed with de novo ALL between 2001 and 2021 from the Cancer in Young People‐Canada registry. The primary outcome was time to serious ON, defined as the time between ALL diagnosis and ON grade ≥ 3 as per CTCAE. Cumulative incidence was estimated using competing risk analysis, and risk factors were evaluated using Cox proportional hazard regression. Result Among 2514 patients, 41 were diagnosed with serious ON, yielding a 5‐year cumulative incidence of 1.73 ± 0.27%. Age ≥10 years, female sex, T‐cell immunophenotype, high‐risk ALL, corticosteroid type (prednisone vs. dexamethasone or combined), and hematopoietic stem cell transplant (HSCT) were significantly associated with serious ON in univariate analysis, while age ≥10 years (adjusted hazard ratio [aHR] = 7.40, 95% confidence interval [CI] = 3.29–16.69) and female sex (aHR = 2.69, 95% CI = 1.42–5.09) remained independently associated with serious ON in multivariable analysis. Asparaginase formulation, race, obesity, and thrombotic events were not associated with serious ON. Conclusion Nearly 2% of children with ALL developed serious ON. Children older than 10 years and females were at the highest risk. Understanding these risk factors is crucial for identifying high‐risk patients, though optimal preventive interventions remain to be established.