Physical Functioning Report and Pulmonary Function Deficit in Childhood and Adolescent Acute Lymphoblastic Leukemia...

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.

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.

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).

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.