Characteristics, survival, and causes of death in patients with APL from Chile

Abstract

Abstract Background: Acute promyelocytic leukemia (APL) is prevalent in Latin America and carries a high risk of early-onset complications. However, outcome data for APL in this region are limited. Since 2020, Chile has adopted all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as the standard therapy for APL. In this real-world study, we describe the characteristics, survival outcomes, and causes of death (COD) for adult APL patients in Chile. Methods: This multicenter, retrospective study analyzed data from 174 adult patients diagnosed with APL across 16 public institutions in Chile between 2013 and 2024. Causes of death were obtained from electronic medical record reviews and death certificates. Time-to-event analyses were conducted using the log-rank test and Kaplan-Meier survival estimates. Results: Of the 174 patients, 90 (52%) were male. The median age at diagnosis was 41 years (IQR: 32–56). Patient distribution by region was as follows: Metropolitan (56%), Biobío (14%), Valparaíso (8.6%), and Antofagasta (6.9%). The incidence of APL was higher in the northern region of Antofagasta at 2 cases per 100,000 inhabitants, compared to a range of 0.9–1.2 per 100,000 in other regions. The t(15;17) translocation was confirmed in 149 patients (86%). Trisomy 8 was found in 21 patients (12%), and a complex karyotype was present in 16 patients (9.2%). The median overall survival (mOS) for the cohort was 2.55 years (IQR: 0.8–5.6). In the multivariate analysis, sex, year of diagnosis, and other cytogenetic abnormalities were not statistically significant predictors of survival (p>0.05). At the time of analysis, 39 patients (22%) were deceased. Of these deaths, 29 (74%) occurred within the first 30 days (early mortality). The proportion of early deaths was 78% (22 of 28 total deaths) prior to the adoption of the ATRA/ATO regimen, compared to 63% (7 of 11 total deaths) after its adoption. The most common COD were bleeding (n=14, 48%), respiratory failure (n=4, 14%), and sepsis (n=2, 6.9%). Conclusion: In this cohort, mortality was primarily driven by early complications, particularly bleeding and respiratory failure. The higher incidence of APL in the Antofagasta region warrants further investigation. Although the adoption of ATRA/ATO lowered overall mortality, early deaths from bleeding remains high. Early recognition of and intervention for coagulopathy are critical to improving survival outcomes in this population