Abstract / Summary
Acute lymphoblastic leukemia (ALL) exhibits regional disparities, but the altitude-stratified observational pattern on population-level mortality remains underexplored. This nationwide ecological study investigated the association between altitudinal gradients and cause-specific ALL mortality across Ecuador (2011–2022). We analyzed 3074 ALL-related deaths (ICD-10: C91.0) extracted across 221 Ecuadorian cantons using the National Institute of Statistics and Censuses mortality register (2011–2022), official cantonal elevations, and 2010 census data. To evaluate macro-environmental trends and prevent rate instability from low event counts in smaller administrative units, cantons were pooled into six 500-m altitudinal strata: Sea Level (< 500 m, baseline), Low (500–999 m), Moderate Low (1000–1499 m), Moderate (1500–1999 m), Moderate High (2000–2499 m), and High (≥ 2500 m). Average annual age-specific mortality rates (ASpMR per 100,000) with exact Poisson 95% confidence intervals were calculated, disaggregated by age (pediatric: <18 years; adult: ≥18 years) and biological sex. Mortality Rate Ratios (MRRs) with 95% log-Wald confidence intervals evaluated relative differences across pooled strata compared to baseline. Adult populations above 2000 m experienced significantly elevated ALL mortality rates compared to sea-level residents. Rates peaked at Moderate High altitudes (2000–2499 m; men MRR: 2.02, 95% CI: 1.67–2.45, p < 0.001; women MRR: 1.83, 95% CI: 1.50–2.23, p < 0.001) and remained higher at High altitudes (≥ 2500\ m; men MRR: 1.72, 95% CI: 1.50–1.97, p < 0.001; women MRR: 1.65, 95% CI: 1.43–1.90, p < 0.001). Conversely, pediatric cohorts showed inverse patterns at lower elevations. Pediatric males demonstrated lower mortality rates at Low (500–999 m; MRR: 0.59, 95% CI: 0.39–0.90, p < 0.05) and Moderate Low tiers (1000–1499 m; MRR: 0.43, 95% CI: 0.19–0.97, p < 0.05). Pediatric females showed lower mortality rates exclusively at the Moderate Low tier (MRR: 0.31, 95% CI: 0.10–0.97, p < 0.05). Residence at higher altitudes correlates with higher adult ALL mortality rates, whereas pediatric cohorts display age-dependent inverse patterns. Regional health planning across the Andes must account for high-altitude geographical differences. These findings highlight potential biological mechanisms—such as hypoxia-inducible factor pathways—warranting prospective studies integrating individual-level clinical, genetic, and socioeconomic data.