Physical Functioning Report and Pulmonary Function Deficit in Childhood and Adolescent Acute Lymphoblastic Leukemia Survivors: A National Cross-Sectional ALL-STAR Lungs Study.
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BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors face an increased risk of pulmonary function deficit (PFD), which may affect physical functioning. We aimed to evaluate parent proxy- and self-reported physical functioning and the association with PFD and abnormal bronchodilator response ( + BDR) among survivors versus controls. METHODS: This cross-sectional study (February 2019-May 2024) included N = 184 ALL survivors (aged 5-17.9 years) from a national NOPHO ALL2008 protocol-treated cohort (eligible, N = 295) ( ≥ 1 year after treatment cessation) and 207 controls. Physical functioning was assessed using the Paediatric Quality of Life Inventory (PedsQL) questionnaire. Pulmonary function tests (PFTs) identified PFD (abnormal PFT) and +BDR according to ERS/ATS criteria. Ordinal logistic regression and t-test compared groups. RESULTS: ALL survivor parents proxy-reported significantly poorer physical functioning than controls (mean difference [MD] -13.3 95% CI [-16.3; -10.3] to MD -10.3 [-17.2; -3.3], p < 0.001 to p = 0.004), but clinically significant impairments were restricted to parent proxy-reports from survivors treated with high-risk (HR) chemotherapy (MD -19.9 [-29.0; -10.7] to -11.5 [-17.5; -5.6], p < 0.001) and stem cell transplantation (HR-SCT) (MD -24.7 [-30.1; -19.4] to -16.9 [-27.4; -6.5], p < 0.001 to p = 0.002) as well as self-reports from HR (MD -11.2 [-18.9; -3.4], p = 0.006) and HR-SCT survivors (MD -14.5 [-24.1; -4.8], p = 0.004). Among 5-15-year-olds, PFD/ + BDR was associated with significantly poorer parent proxy-reported physical functioning in survivors versus controls (MD -14.3 [-21.2; -7.3], p < 0.001). Significant deficits in these groups related to running, engaging in sports/exercise and lifting heavy objects. PFD/ + BDR was not associated with poorer physical functioning reports within survivors (MD -2.5 [-9.0; 3.3] to 0.1 [-13.7; 13.8], p = 0.36-0.99). CONCLUSIONS: Physical functioning in survivors compared to controls varies with intensity of treatment, most evident in HR and HR-SCT survivors, with impairments linked to PFD and +BDR in the youngest. Among survivors, physical functioning did not align with PFD and +BDR status, highlighting the need for parallel assessment of objective and subjective measures during follow-up. Baseline PFT and tailored follow-up are essential for high-risk groups, to detect PFD early and intervene.