Venous Thromboembolism Following L-Asparaginase Treatment in Hematologic Malignancies in Korea
Authors: Lee Ji Hyun , Yhim Ho-Young , Bang Soo-Mee 
Published: October 2019

Abstract
Background: L-asparaginase (L-asp) is one of the important drugs to make the change of cure higher in acute lymphocytic leukemia (ALL) and some lymphomas. The risk of thrombosis in ALL patients after L-asp use is known to be 2.4-5.4% in pediatric and 5.9-34% in adult. Although the prevalence of venous thromboembolism (VTE) in Asian is generally lower compared with Western populations, there are few reports about the incidence of VTE in Asian patients with hematologic malignancies treated with L-asp. In this study we performed a nationwide population-based epidemiologic study to provide basic information regarding the incidence rate and risk factors of VTE in Korean patients with hematologic malignancies after L-asp treatment.
Methods: Using the Korean Health Insurance Review and Assessment Service (HIRA) database, patients treated with L-asp from 2009 to 2013 were retrospectively identified by medication codes. The National Health Insurance (NHI) is the only public medical insurance system operated by the Ministry for Health, Welfare and Family Affairs in Korea. The NHI program of Korea covers the whole population as a compulsory social insurance system. Therefore, there are no exceptions for seasonal, part-time or unemployed workers. HIRA is a government-affiliated organization to build an accurate claims review and quality assessment system for the NHI. According to data from the Korean Statistical Information Service (http://kosis.kr/) the Korean population was 48 580 293 in 2010. Also, according to data from the NHI, the registered populations was 50 581 000 in 2010. There is a difference in population figures between data from the Korean National Statistical Office and the NHI because of overseas Koreans. A population-based study was possible for this study because the NHI basically covers all Korean residents and also the population itself is ethnically homogeneous. The HIRA database includes both hospitalization cases and outpatient clinic cases. All cases were included in the study when there was evidence of L-asp treatment. Among the cases with L-asp, VTE cases which has occurred after L-asp treatment were identified when the starting date of the VTE diagnostic codes was between the start date of L-asp and 3 months after the end of L-asp treatment.
Results: During the year 2009 to 2013, a total of 3304 patients were prescribed with colaspase in any type of hematologic malignancies including ALL and lymphoma. Patients who were treated with pegarspase or crisantaspase were not included. Among the 3304 patients, 118 patients (3.57%) had occurred VTE. The most common site of thrombosis was upper extremities (44/118 = 37.29%) followed by deep vein (30/118 = 25.42%) and pulmonary artery (30/118 = 25.42%), inferior vena cava (6/118 = 5.08%), portal vein (3/118 = 2.54%), cerebral sinus (2/118 = 1.69%), renal vein (2/118 = 1.69%), and splenic vein (1/118 = 0.85%). Among the 1809 patients 18 years or younger, 37 patients (2.05%), and among the 1501 patients 19 years of older, 81 patients (5.39%) suffered from VTE (P < 0.0001). Other factors including gender, disease (ALL or lymphoma), type of steroids (prednisone or dexamethasone) and use of anthracyclines did not appear to be associated with VTE after L-asp treatment.
Conclusions: This is the largest epidemiologic study in Asian patients with hematologic malignancies with L-asp treatment. The incidence of thrombosis after L-asp use was comparable with Western populations, and the risk was higher in adults compared with pediatrics. Concomitant use of prednisone and anthracyclines did not affect VTE occurrence.

Disclosures
No relevant conflicts of interest to declare.