Late pulmonary adverse effects in childhood and adolescent acute lymphoblastic leukaemia survivors: a cross-sectional ALL-STAR Lungs study

BACKGROUND: Childhood acute lymphoblastic leukaemia (ALL) survival rates have improved, reaching 95%. However, 25-50% of survivors experience significant treatment-related toxicities. This study investigated late pulmonary adverse effects, including pulmonary symptoms and pulmonary function, in childhood ALL survivors compared to controls.

METHODS: This Danish national cross-sectional study (February 2019 to May 2024) recruited ALL survivors (n=295 eligible) and matched controls 1:1 for pulmonary symptom questionnaire and pulmonary function tests (PFTs): nitrogen multiple breath washout, spirometry, impulse oscillometry, bronchodilator response, diffusing capacity of the lung for carbon monoxide (D LCO) and nitric oxide (D LNO).

RESULTS: Among 192 survivors and 213 controls performing PFTs, 185 survivors and 209 controls had valid PFTs included in analyses. Prevalences of resting and exertional dyspnoea in survivors (2% and 14%, respectively) versus controls (0% and 3%, respectively) were highest among survivors treated with high-risk chemotherapy (HR) (6% and 18%, respectively) and high-risk chemotherapy followed by stem cell transplantation (HR-SCT) (5% and 26%, respectively). Compared to controls, HR and HR-SCT survivors had impaired mean z-scores for forced expiratory volume in 1 s (-1.64 and -0.37, respectively, versus 0.28), forced vital capacity (-1.66 and -0.67, respectively, versus 0.20), D LNO (-2.39 and -2.55, respectively, versus 0.97) and HR-SCT survivors: lung clearance index (3.31 versus 0.52) and D LCO (-1.23 versus 0.12).

CONCLUSIONS: We found a higher reported prevalence of exertional dyspnoea and impaired pulmonary function in HR and HR-SCT survivors compared to controls. Reassuringly, non-HR/HR-SCT survivors demonstrated pulmonary function comparable to peers. The findings highlight the need for timely detection and tailored monitoring of pulmonary function deficit to improve pulmonary health in HR and HR-SCT survivors.