Pulmonary Function Deficit and Clinical Associations in Childhood Acute Lymphoblastic Leukaemia Survivors: A National Retrospective ALL‐STAR Lungs Cohort Study

BACKGROUND: Although survival for childhood acute lymphoblastic leukaemia (ALL) has improved, long-term pulmonary function deficit remains a concern. We aimed to explore the prevalence of pulmonary function deficit and abnormal pulmonary function tests in childhood ALL survivors and clinical associations. METHODS: This national, retrospective cohort study (February 2019-May 2024) included eligible 5-17.9 year-old survivors (N = 295) who performed a valid pulmonary function test ≥ 1 year after treatment (N = 185). Clinical associations included treatment characteristics, pulmonary diagnosis, and radiological findings from medical charts. RESULTS: Among 185 survivors, 37% (95% confidence interval (CI): [30, 45]) had pulmonary function deficit, with the highest prevalence (56%) among 15-17.9-year-olds. Abnormal test prevalence was 37% [27, 48] for diffusing capacity (carbon monoxide and/or nitric oxide), 29% [22, 38] for lung clearance index, 12% [8,18] for forced expiratory volume in the first second, and 11% [7, 17] for broncho-dilator response. Bronchiolitis obliterans, stem cell transplantation and CT-verified bronchiectasis were significant clinical associations of pulmonary function deficit (100%, 97.5% CI: [40, 100], 89% [76, 103], 73% [51, 96]) and abnormal diffusing capacity (100% (97.5% CI [29, 100]), 82% [59, 105], 75% [45, 105]), respectively. Bronchiectasis (88% [65, 110]) and transplantation (64% [39, 89]) were associated with a higher prevalence of abnormal lung clearance index. Bronchiolitis obliterans (75% [19, 99]) and transplantation (61% [39, 84]) were associated with a higher prevalence of abnormal forced expiratory volume in the first second. CONCLUSIONS: Pulmonary function deficit was frequent in childhood ALL survivors, especially after stem cell transplantation or pulmonary disease. Tailored long-term pulmonary monitoring, including small airway function and diffusing capacity, may aid in timely detection and intervention.