Abstract
Background: Acute promyelocytic leukemia (APL) is a distinct and highly curable subtype of acute myeloid leukemia. Despite the availability of effective contemporary therapies, such as all-trans retinoic acid and arsenic trioxide (ATO), survival disparities persist, driven by differences in healthcare access, disease severity, and patient characteristics. Moreover, real-world data on APL outcomes in the Middle East are scarce. This study aims to evaluate the clinical characteristics, treatment patterns, and outcomes of APL patients in Qatar, a country with a small geographic size, a young population, and a government-funded healthcare system. Methods: We conducted a single-center, retrospective cohort study of adult patients diagnosed with APL at the National Center for Cancer Care and Research between 2012 and 2024. Data from electronic medical records were analyzed for demographics, clinical factors, treatment, and outcomes like response, early death, bleeding, and relapse. Kaplan-Meier and log-rank tests were used to assess survival, while Cox regression identified predictors of overall survival (OS). Results: Eighty-seven adults diagnosed with APL were included. The majority were male (82.8%), with a median age of 36 years (range, 28–42.5). Most patients were of Asian origin (67.8%), followed by Arab descent (26.4%). Comorbidities were present in 21.8% of patients, with hypertension being the most common (36.4%). According to Sanz's risk stratification, 47% were classified as high-risk, and 53% as low/intermediate risk. Common presenting symptoms included fever (48.3%) and bleeding (34.5%). Neurological manifestations and disseminated intravascular coagulation were reported in 11.5% and 53% of patients, respectively. The mean platelet count, white blood cell count, international normalized ratio, and fibrinogen level were 29.3 × 10⁹/L (range: 3–164), 31.6 × 10⁹/L (range: 0.3–292.9), 1.41 (range: 1–2.9), and 3.2 g/L (range: 0.14–52), respectively. Seventy-one patients received APL treatment. The used regimens were PETHEMA (n = 33), Lo-Coco (n = 23), APML4 (n = 13), and other protocols (n = 2). Among 62 evaluable patients after first induction, 79.0% achieved complete remission (CR), with the highest rate in the Lo-Coco group (86.4%). Treatment-related complications occurred in 83.1% of patients, including infections (66.2%), bleeding (22.5%), differentiation syndrome (21.1%), QT prolongation (16.9%), and thrombosis (12.7%). Overall, 33% of patients were admitted to the ICU, with a median stay of 5 days. Treatment was discontinued due to toxicity (n= 6), patient request (n= 3), repatriation (n= 3), or treatment failure (n= 1). Relapse occurred in 5 patients, two of whom underwent stem cell transplantation. At the end of follow-up, 63 patients (72.5%) were alive, with an overall mortality rate of 27.5%. The incidence of mortality declined from 10 to 8 per 1,000 person-years when comparing the 2012–2018 cohort to the 2019–2024 cohort. Early death occurred in 22 patients, with a median time to death of 4 days. Most early deaths were observed in high-risk Sanz patients (73.9%) and were significantly associated with major bleeding (56.7% vs. 12.3% in non-bleeding patients; p < 0.001). Central nervous system (CNS) bleeding was the leading cause of early death (n= 15). Early mortality rates were 32.6% between 2012–2018 and 20.5% between 2019–2024 (p= 0.20). Kaplan-Meier analysis showed a mean OS of 104 months (95% CI: 81.2–120.5), with significant differences across Sanz risk categories (p= 0.001). The median OS was not reached in either group. Patients treated after 2019 had a higher survival rate (82% vs. 58%), likely reflecting the adoption of urgent diagnostics and ATO-based regimens. Multivariate analysis identified ICU admission (HR= 6.07, p= 0.009) and receiving treatment (HR= 0.116, p= 0.001) as independent predictors of survival. Conclusion: This real-world cohort reinforces the efficacy of contemporary APL treatment with high remission, low relapse rates, and improved OS since ATO-based regimens were introduced. However, early mortality, primarily driven by hemorrhagic complications, remains a major barrier to optimal outcomes. Our findings underscore that, even in a young and low-comorbidity population, early-phase complications persist. Timely diagnosis, rapid initiation of therapy, and enhanced supportive care remain critical to reducing early deaths and maximizing therapeutic success.
