S308: risk factors for venous thromboembolism in acute promyelocytic leukemia

Background: Acute promyelocytic leukemia (APL) is frequently associated with disseminated intravascular coagulation (DIC) leading to potentially life threatening bleeding. Compared to bleeding, thromboses are a less commonly encountered problem, and data about the epidemiology of venous thromboembolism (VTE) in APL stems mainly from individual case reports. Aims: to identify the incidence and predictive value of demographic and clinical-laboratory parameters for VTE in APL patients. Methods: We conducted a retrospective study that included adult patients diagnosed with APL between 2006 and 2023 in Clinic of Hematology UCCS, treated with all-trans retinoic acid (ATRA) and anthracycline. Demographic and clinical-laboratory data related to the VTE were collected. In order to identify the risk factors of VTE, univariate and multivariate analysis were performed. We analyzed the following parameters as predictors of VTE: age, sex, Body Mass Index (BMI), previous thrombosis, comorbidities, Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG-PS), white blood cell (WBC) count, hemoglobin (Hb), platelet count, fibrinogen, prothrombin time (PT), promyelocyte and blast count, activated partial thromboplastin time (APTT), D-dimer level, International Society on Thrombosis and Haemostasis (ISTH) DIC score at diagnosis, APL risk group, cytological type, presence of immunophenotypic characteristics (CD114, CD64, CD38, CD2, CD15, CD11c, CD56, CD7, CD19), karyotype, PML-RARa variant, bleeding and the occurrence of a differentiation syndrome. We also analyzed the predictive value of Al-Ani thrombosis risk assessment model (RAM) in our group of patients. Results: Among 134 adult APL patients, VTE was diagnosed in 23 patients (17.2%), with mean age of 47 years (± 15 years) and sex-ratio of 1. The VTE was present at the time of APL diagnosis in 3 (15%) patients, while occurring during induction and consolidation cycles in 8 (40%) and 9 (45%) patients, respectively. Most common thrombosis localization was central venous catheter (CVC) thrombosis in 9 (45%) patients, 4 (20%) patients had a deep vein thrombosis (DVT), 1 (5%) patient had Budd-Chiari syndrome, while other localizations were present in 6 (30%) patients. Venous thromboembolism was not the cause of any death. Among analyzed parameters, patients with VTE had significantly higher PT value (p=0.02, 75% vs 63%), lower ISTH DIC score (p=0.031, 5 vs 6), higher CD114 expression (p=0.009, 63.6% vs 33.7%) and had less frequently mild to severe bleeding at diagnosis (p=0.01, 78.3% vs 93.7%). Our analyses also showed Al-Ani RAM predictive of VTE in patients with APL (p=0.046). The independent risk factor for VTE, identified through the multivariate analysis was CD114 expression (p=0.015, OR=3.867, IC 95%: [1.3-11.4]). Summary/Conclusion: The risk of VTE in APL patient is high and should not be underestimated. To best of our knowledge, this is the first study that showed a predictive value of Al-Ani RAM and CD114 expression in patients with APL and thrombosis, but further analyses will be needed to confirm those findings and help make therapeutic strategy to prevent potentially fatal VTE complications. Keywords: Acute promyelocytic leukemia, Venous thromboembolism, Risk factor