Social determinants outweigh geographic barriers in Acute Myeloid Leukemia survival: Insights from a brazilian multicenter study

Abstract

Abstract Introduction: Studies from European and North American cohorts have shown that the distance from patient's home from the treatment center is not associated with overall survival in acute myeloid leucemia (AML). However, in a country with continental dimensions and markedly deeper socioeconomic disparities such as Brazil, this question had not yet been addressed. This is the first multicenter study to evaluate the impact of both the distance from a patient's residence to the hospital and the Human Development Index (HDI) of their neighborhood on AML mortality. Methods: This study enrolled patients from the Brazilian Acute Myeloid Leukemia Registry, a national ambispective study involving patients aged 18 years or older with a diagnosis of AML without previous treatment (excluding acute promyelocytic leukemia and leukemias of ambiguous lineage). These patients were treated in either public or private healthcare centers. The study was supported by the Brazilian Association of Hematology, Hemotherapy, and Cellular Therapy (ABHH). Prognostic stratification followed the European Leukemia Net (ELN) 2022 guidelines. The distance between residence and hospital was calculated using the Euclidean (straight-line) approach, with ZIP-code centroids as proxies for each location, and categorized into three groups: less than 30 km, between 30–40 km, and more than 40 km. HDI for each neighborhood or city was obtained from a national public database. Patients were divided into HDI ≥ 0.8 and HDI < 0.8 groups, with 0.8 recognized by the United Nations Development Programme (UNDP) as the threshold for “very high human development.”. Results: A total of 321 patients were analyzed, with 44 (14%) residing less than 30 km from their reference hospital, 169 (53%) between 30–40 km, and 108 (33%) more than 40 km away. Among patients in the group with an HDI above 0.8, 64% received intensive chemotherapy–based treatment and 28% received venetoclax with hypomethylating agents. Similarly, among those residing in regions with an HDI below 0.8, 57% received intensive chemotherapy and 22% received venetoclax with hypomethylating agents. Regarding risk stratification according to ELN 2022, 18% of the patients had a favorable prognosis, 46% an intermediate prognosis, and 36% an adverse prognosis. With a median follow-up of 32.2 months, the 3-year overall survival was 26.8% (95% CI, 21.6–33.3%), being 20.2% among those living in areas with HDI < 0.8 and 38.2% among those with HDI ≥ 0.8. Being treated in a public center instead of a private center was independently associated with na increased risk of mortality (HR 2.56; 95% CI 1.90 – 3.70, p<0.0001). In our analysis, the distance between a patient's residence and their reference hospital did not emerge as a relevant risk factor for overall mortality, early mortality, or mortality beyond 30 days. In contrast, the HDI of the patient's residential area proved to be an important determinant of outcomes. In the multivariate analysis, living in areas with higher HDI was significantly associated with a lower risk of death (HR 0.62; 95% CI 0.44–0.86; p = 0.0052). Even after adjusting for age, ELN 2022 risk stratification, and treatment in a public versus private hospital, HDI remained a protective factor (HR 0.65; 95% CI 0.44–0.86; p = 0.0015). Regarding barriers to hematopoietic stem cell transplantation, among the 124 patients deemed eligible for allogeneic transplantation, 61.4% of those residing in very high-HDI neighborhoods received the therapy, compared with only 38.4% of those living in areas with HDI < 0.8. This discrepancy was confirmed by chi-square analysis (p = 0.034). Conclusions: These findings suggest that, beyond geographic barriers, social and structural determinants—such as the HDI of the residential area and reliance on the public health system—significantly influence survival and access to high-complexity treatments in AML. Patients from regions with higher socioeconomic development appear more likely to receive potentially curative therapies, such as allogeneic stem cell transplantation, possibly due not only to better hospital infrastructure and greater availability of transplant beds, but also to stronger financial and social support systems, contributing to improved clinical outcomes regardless of travel distances to the hospital.