PB1803: EARLY DEATH IN ACUTE PROMYELOCYTIC LEUKEMIA: DEFINING HIGH RISK PATIENTS

Background: Acute promyelocytic leukemia (APL) is a rare type of leukemia characterized by its good prognosis, thanks to the introduction of all-trans retinoic acid (ATRA). However, early mortality (death within 30 days of the start of treatment) remains a challenge to undertake. Aims: The objective of this study was to identify the causes and risk factors of early death (ED) in APL patients treated with ATRA and anthracycline. Methods: We retrospectively collected the data relative to the patients diagnosed with APL in our department between 2010 and 2019, who received an induction treatment consisting of ATRA and Idarubicin, according to the PETHEMA protocols: LPA 99 (2010-2013) and LPA2005 (2014-2019). A statistical analysis was performed, aiming to define ED risk factors. Results: A total of 90 patients were included in our study. ED was observed in 17 patients (19%), characterized by a sex ratio of 0.89 and a median age of 40 (4 - 71 years). The main cause of ED was represented by severe hemorrhage (11 patients, 65%), followed by differentiation syndrome (3 patients, 18%). The ED was due to a septic choc, a thrombotic event, and a leucostasis, for one patient each. The correlation between certain clinical and biological parameters and ED was analyzed. The clinical parameters studied were: age, gender, delay between onset of symptoms and treatment, Performance Status (PS), treatment protocol, Sanz Score, clinical presentation, severe bleeding during induction, thromboembolic events (TE), and differentiation syndrome (DS). The biological parameters studied were: White Blood Cell (WBC) count, platelets, hemoglobin, LDH level, creatinine clearance, prothrombin time (PT), fibrinogen, presence of Disseminated Intravascular Coagulation (DIC) at diagnosis, cytological type, PML/RARA variant, and the presence of additional cytogenetic abnormalities. A statistically significant difference was found for the following risk factors: PS higher than 1 (p<0.0001; 71% vs 14%), Sanz score (p=0.005; 71% at high risk vs 29%), WBC count(p<0.0001; median of 26.03G/L in the ED group versus 2.5G/L), LDH level(p=0.001; a mean of 732 versus 372), prothrombin time (p=0.011; a median of 55% versus 70%), fibrinogen level less than 1g/L (p=0.05; 35% vs 15%), presence of a TE at diagnosis (p=0.004; 18% vs 1.4%), and occurrence of severe bleeding complication during induction (p<0.0001; 61% vs 39%). The independent risk factors of ED identified through the multivariate analyses were: PS (p=0.001, OR=41.6, IC95% [4.7-363], and severe bleeding during induction (p<0,0001, OR=71.5, IC95% [7.1 - 716.3]). Summary/Conclusion: Our results are comparable to those of the literature. ED mainly due to severe bleeding, is a major obstacle in the management of APL. The identification of its risk factors allows us to improve the therapeutic strategies. The implementation of a supportive therapy, as soon as the diagnosis is suspected, seems to be an adequate measure to tackle this challenge.