PB1768 PREDICTIVE FACTORS OF SEVERE BLEEDING IN ACUTE PROMYELOCYTIC LEUKEMIA

Abstract

Background:Acute promyelocytic leukemia (APL) is identified by the predomination of abnormal promyelocytes in the bone marrow (BM) and a specific chromosomal translocation – t(15;17) – resulting in a fusion transcript between the promyelocytic (PML) gene on chromosome 15 and the retinoic acid receptor alpha (RARα) gene on chromosome 17; this transcript is known as PML–RARα. The t(15;17) chromosomal translocation can cause hyperexpression of tissue factor (TF) in cells of patients with APL and render the patient hypercoagulable.Aims:The objective of the current study was to assure more appropriate therapeutic strategies for reducing severe hemorrhaging by assessing the recovery of abnormal coagulation indexes in patients with acute promyelocytic leukemia (APL) during induction therapy.Methods:Retrospective analyses of newly diagnosed with APL were performed during initial treatment. A total of 23 patients newly diagnosed with APL were treated at the Hematology department of Emergency Hospital (Semey, Kazakhstan), between April 2008 and January 2019. This cohort included 9 males and 14 females with a median age of 41 years (range: 12–75). The APL diagnostic criteria were based on the World Health Organization Classification of Tumors–Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues (2008) and French–American–British classification systems (1976) criteria. A molecular diagnosis was confirmed by identification of t(15;17) in a cytogenetic analysis and/or positive detection of PML–RARα using either fluorescence in situ hybridization or reverse transcription‐polymerase chain reaction. The immune phenotype diagnosis of APL was established by positivity for CD33, CD9, CD13, and CD117, and low expression of HLA‐DR and CD34. Early death (ED) was defined as death due to any cause within 30 days of diagnosiResults:Hemorrhage was the principal cause of death during the induction period. The values of white blood cell count, lactate dehydrogenase, prothrombin time (PT), fibrinogen (Fbg), hemoglobin, and bone marrow leukemic promyelocytes were significantly different in the high‐risk group compared to the low/intermediate‐risk groups. There were significant differences in the white blood cell count, bone marrow leukemic promyelocytes, platelet (PLT) count, and the levels of lactate dehydrogenase, d‐dimer, PT, and Fbg, as well as in FLT3‐ITD mutations between patients with major bleeding and those with minor bleeding. Hemostatic variables significantly improved over time during induction therapy. The recovery times of the PLT, PT, and Fbg values were significantly slower in patients with major bleeding than in those with minor bleeding. Particularly, the PLT level in patients with major bleeding was not similar to that in the minor bleeding group until after 4 weeks of treatment. Hemorrhages were the most common cause of induction death in this study. High‐risk patients were more prone to serious clinical bleeding symptoms. Patients with major bleeding had more rapid proliferation characteristics and an increased incidence of FLT3‐ITD mutations compared to patients with minor bleeding. Hemostatic variables recovered significantly more slowly in patients with major bleeding than in those with minor bleeding. Active induction therapy and blood product infusion are efficient in preventing severe bleedingSummary/Conclusion:Our results suggested that low PLT count might be the leading cause of fatal bleeding in patients newly diagnosed with APL.