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

Objectives To examine morbidity and mortality in survivors of childhood acute lymphoblastic leukaemia (ALL) across their teenage and young adult (TYA) years; comparing the patterns observed with individually matched general population controls. Design Case-control study with follow-up linkage to administrative healthcare databases for up to 25 years. Setting The study population comprises all children (0-14 years) registered for primary care with the National Health Service (NHS) in England 1992-1996. Participants 1082 five-year survivors of ALL diagnosed <15 years of age, and 2018 age- and sex-matched population-based controls; followed to 15 March 2020. Main outcome measures Associations with hospital activity, cancer, and mortality were assessed using incidence rate ratios and absolute risk difference. Results Mortality 5-25 years after diagnosis was 20 times higher in cases than controls (Rate Ratio 21.3, 95% Confidence Interval 11.2-45.6), and cancer incidence 10 time higher (IRR 9.9 95% CI 4.1-29.1). Hospital activity was increased for many clinical specialties, the strongest effects being for endocrinology; outpatient IRR 36.7, 95% CI 17.3-93.4 and inpatient 19.7, 95% CI 1.9-25.5 for males, and 11.0, 95% CI 6.2-21.1 and 6.2 95% CI 3.1-13.5 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, ENT (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 a large excess risk of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years. Involving most clinical specialties, the observed effects are striking, showing no signs of diminishing over the first 25 years of follow-up. These findings underscore the need to take prior ALL drug and/or radiation treatment into account when interpreting seemingly unrelated symptoms in later life.