Excess morbidity and mortality among survivors of childhood acute lymphoblastic leukaemia: 25 years of follow-up from the United Kingdom Childhood Cancer Study (UKCCS) population-based matched cohort

OBJECTIVES: To examine morbidity and mortality among teenagers and young adults (TYAs) previously diagnosed with acute lymphoblastic leukaemia (ALL) in childhood, and compare to the general TYA population. DESIGN: National population-based sex-matched and age-matched case-control study converted into a matched cohort, with follow-up linkage to administrative healthcare databases. SETTING: The study population comprised all children (0–14 years) registered for primary care with the National Health Service (NHS) in England 1992–1996. PARTICIPANTS: 1082 5-year survivors of ALL diagnosed<15 years of age (1992–1996) and 2018 unaffected individuals; followed up to 15 March 2020. MAIN OUTCOME MEASURES: Associations with hospital activity, cancer and mortality were assessed using incidence rate ratios (IRR) and differences. RESULTS: Mortality in the 5-year ALL survivor cohort was 20 times higher than in the comparison cohort (rate ratio 21.3, 95% CI 11.2 to 45.6), and cancer incidence 10 times higher (IRR 9.9 95% CI 4.1 to 29.1). Hospital activity was increased for many clinical specialties, the strongest associations being for endocrinology; outpatient IRR 36.7, 95% CI 17.3 to 93.4 and inpatient 19.7, 95% CI 7.9 to 63.2 for males, and 11.0, 95% CI 6.2 to 21.1 and 6.2 95% CI 3.1 to 13.5, respectively, for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology; ear, nose and throat; urology; and dermatology, while females were more likely to be seen in plastic surgery and less likely in midwifery. CONCLUSIONS: Adding to excess risks of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years, which is not related to routine follow-up monitoring. Involving most clinical specialties, associations are striking, showing no signs of diminishing over time. Recognising that all survivors are potentially at risk of late treatment-associated effects, our findings underscore the need to take prior ALL diagnosis into account when interpreting seemingly unrelated symptoms later in life.