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.