Disparities in survival and therapy access in AYA acute lymphoblastic leukemia: A real-world analysis of social determinants in a low- and middle-income country

Abstract Background: Health disparities in low- and middle-income countries may impact access to care and survival in patients with acute lymphoblastic leukemia (ALL), especially among adolescents and young adults (AYA). Social determinants such as the Human Development Index (HDI) and income inequality (GINI coefficient) are rarely analyzed in relation to treatment deviations or access to advanced therapies. Aims: To evaluate the association of HDI and GINI with overall survival, access to advanced therapies, and treatment deviations in a Mexican AYA cohort with Philadelphia-negative (Ph-neg) B-ALL treated with the pediatric-inspired CALGB 10403 regimen. Methods: This was a retrospective cohort study including newly diagnosed Ph-neg B-ALL patients treated between 2017 and 2024 in a single tertiary center. HDI and GINI values were obtained from national data and were matched to patient data based on municipality of residence at diagnosis. HDI reflects levels of health, income, and education, with higher values suggesting better overall development. The GINI coefficient measures income inequality, with higher coefficients reflecting greater income inequality. Survival outcomes were estimated using Kaplan-Meier analysis. Cox regression models were used to assess prognostic factors. Treatment deviation was defined as omission of ≥2 asparaginase cycles not attributable to toxicity. A subgroup analysis was performed in patients who completed the intensive phase of therapy without relapse or death. Results: One hundred and four patients were included. Median age was 28 years (IQR 21–37), 55% were male, and median follow up was 21.48 months. Nineteen patients (18%) lived in areas with low HDI (≤0.668). There were no differences between baseline characteristics according to low vs high HDI. Overall survival at 2 years was significantly lower in patients with low HDI (43.4% vs 70.8%, p=0.016), with a median OS of 18.5 months vs not reached. In multivariable analysis, low HDI remained independently associated with inferior survival (HR 3.27, 95% CI [1.46–7.29], p=0.0039), along with higher age (HR 1.04 per year, p=0.034), higher WBC at diagnosis (HR 1.006 per unit, p<0.001), and measurable residual disease positivity after induction (HR 2.08, p=0.042). Patients who received blinatumomab (n=12) or underwent hematopoietic stem cell transplantation (HSCT) in first remission (n=10) had higher median GINI coefficient (0.399 vs 0.363 for patients who received blinatumomab compared to those who did not [p=0.011], and 0.392 vs 0.373 for patients who received HSCT compared to those who did not [p=0.06]). Among 79 patients who completed intensive therapy without relapse or death, 12 (15%) had treatment deviations. These patients had significantly worse 2-year OS (25% vs 81.7%, p<0.001). Treatment deviation was associated with a 5.88-fold increased risk of mortality (95% CI 2.26–15.29, p<0.001). Although not statistically significant, patients with lower HDI (<0.7505) were more likely to have treatment deviations compared to those with higher HDI (≥0.7505) (25% vs. 8.5%, OR 3.52, 95% CI [0.84-17.71], p=0.059).Conclusions: Lower HDI is independently associated with inferior survival in AYA patients with Ph-neg B-ALL treated with a pediatric-inspired regimen in Mexico. Higher GINI was associated with access to blinatumomab and HSCT, likely reflecting the availability of these therapies in areas with high income inequality, where wealthier patients coexist with underserved populations. Treatment deviations were strongly associated with mortality and may reflect underlying structural and socioeconomic barriers. These findings highlight the need to address social determinants of health in AYA leukemia care in low- and middle-income settings.