Early-onset chronic and metabolic morbidity among survivors of childhood acute lymphoblastic leukemia: Evidence from Middle Eastern real-world data.

Abstract

10049 Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk of long-term morbidity; however, limited data describe the early onset of metabolic and chronic conditions in contemporary cohorts or their association with treatment intensity in real-world settings. Existing evidence largely reflects European or North American populations, historical treatment eras, and fragmented healthcare systems. Data from Middle Eastern populations, particularly within a national health insurance framework enabling longitudinal follow-up across childhood and adulthood, are scarce. This study addresses these gaps by evaluating early-onset metabolic and chronic morbidity among childhood ALL survivors treated across multiple therapeutic eras within Israel’s integrated healthcare system. Methods: We conducted a retrospective cohort study using electronic health records from Clalit Health Services, Israel’s largest integrated payer–provider healthcare system. Five-year survivors of childhood ALL (diagnosed <19 years between 1980–2018) were matched 1:6 to cancer-free controls by age and sex. Chronic conditions were ascertained longitudinally using validated diagnosis codes. Multivariable Cox and logistic regression models estimated associations between ALL survivorship and chronic health outcomes. Among survivors, additional analyses examined associations with treatment intensity, treatment protocol era, and cranial radiation exposure (dose-specific). Results: The cohort included 437 childhood ALL survivors and 2,622 matched controls; survivors were 74.6% Jewish, 18.3% Arab, and 7.1% other ethnicities. Compared with controls, ALL survivors had significantly increased risks of central nervous system conditions (HR 3.65, 95% CI 1.71–7.80), thyroid disorders (HR 2.18, 95% CI 1.55–3.05), cardiovascular disease (HR 2.09, 95% CI 1.35–3.22), diabetes (HR 1.83, 95% CI 1.05–3.21), obesity (HR 1.58, 95% CI 1.31–1.91), and metabolic syndrome (OR 2.09, 95% CI 1.53–2.80). No ethnic differences were found across all chronic conditions. Excess morbidity occurred within the first 2-years of survivorship and persisted through 5- years, except for endocrine that became apparent later. Higher treatment intensity, earlier treatment protocols, and hematopoietic stem cells were associated with greater burden. Conclusions: Childhood ALL survivors experience early and disproportionate accumulation of chronic conditions, at young ages. Leveraging real-world data, this study provides novel evidence that treatment intensity and protocol era strongly shape early survivorship risk; unrelated to type of healthcare or ethnicity. These findings highlight the need for early, risk-adapted surveillance and targeted metabolic prevention strategies in contemporary ALL survivorship.