A scoring system to predict life-threatening thromboischemic events in patients with acute promyelocytic leukemia: the PETHEMA/PALG study

Abstract

Acute promyelocytic leukemia (APL) is a highly curable leukemia characterized by life-threatening coagulopathy leading to hemorrhagic and thrombo-ischemic events. We analyzed the incidence, outcomes and risk-factors of thromboischemic events in a large series of 1210 patients with newly diagnosed APL reported to the PETHEMA registry. Therapy consisted on ATRA and chemotherapy (AIDA-based). Median age of patients was 46 years (range 2-90 years). Fifty-eight patients (5%) did not start AIDA regimen as they were unfit for chemotherapy, or they died early before initiating ATRA. A total of 195 (16%) patients developed thrombo-ischemic events, the most frequent being superficial-vein and/or central catheter-related (6.9%) followed by central nervous system (2.2%), deep-vein thrombosis (2.1%), pulmonary embolism (2.1%), acute myocardial infarction (1.6%), or other locations (1.2%). Thromboischemic events mostly occurred at diagnosis and during induction (4.0%, and 9.3%, respectively). Patients developing life-threatening thrombo-ischemic events (i.e, excluding superficial and/or catheter-related) at diagnosis/induction had 31% early death rate. Prolonged aPTT, age >40 years, ECOG more than 1, platelets > 25 x 109/L, and absence of bleeding at presentation were independent risk factors for life-threatening thrombo-ischemic events. Using these variables (1 point each) we developed and validated the Thromb-On risk score, identifying a high-risk group (3 to 5 points). The Thromb-On risk score was validated in a cohort of 585 patients treated since 2017 with arsenic trioxide plus ATRA (<10x109 leukocytes) or AIDA (≥10x109 leukocytes). This study could help to improve prevention and management of life-threatening thromboischemic events, through risk-adapted guidance, potentially leading to decrease early mortality in APL.