Asparaginase with Thrombotic Complications in Pediatric Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

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Kunanya Suwannaying
Patcharee Komvilaisak
Patcharee Komvilaisak
Busara Charoenwat
Watuhatai Paibool
์Napat Laoaroon

Abstract

Background and Objective: Thromboembolic events (TEEs) Asparaginase is a standard chemotherapy agent which is successful against childhood acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). However, asparaginase increases the risk of Thromboembolic events (TEEs)   This retrospective descriptive study aims to describe the characteristics, treatment, and outcomes of children with asparaginase-related thrombosis in Srinagarind Hospital, Thailand.


Methods: Pediatric ALL and LL patients, aged under 18 years old at diagnosis of ALL and LL with definitely diagnosed TEEs, treated between 1997 and 2017, were retrospectively reviewed. Patient demographic data, clinical presentations of TEE, actual dosage of asparaginase, concomitant anthracycline and steroids administration, imaging study results, treatments, and outcomes, were all collected and analyzed.


Results: Of 831 ALL and LL patients, 16 developed asparaginase-related TEE. Median age of patients with TEE were 12 years (range 3-15 years). CNS thrombosis (14 patients).was the mont com mon, venous sites more than  arterial sites (62.5% versus 37.5%). Seizures were the most common presentation, with a median time of onset of 17 days from the first exposure (range 1–41 days). Most of them  received anthracycline and steroids during asparaginase administration. Acquired protein S deficiency was the most common prothrombotic state, followed by acquired antithrombin and acquired protein C deficiency. Most patients were treated with low-molecular weight heparin (81.1%). Of 8  patients had complete responses, 4 had partial responses, and thad clinical improvement  Ten of 14 patients (71.4%) with CNS TEE had favorable outcomes (modified Rankin scale 0-1). Twelve patients (75%) were alive, two died from advanced cancer, and one died from brain herniation after cerebral infarction.


Conclusions: Caution is necessary concerning asparaginase-related TEE in leukemia and lymphoma patients, particularly in patients aged more than 10 years old. Protein S deficiency was the most risk factor  Post-TEEs treatment had favorable outcomes. Rechallenge of asparaginase is rather safe. Further larger prospective studies focusing on risk factors and TEEs prophylaxis studies should be conducted to improve outcomes. 

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1.
Suwannaying K, Komvilaisak P, Komvilaisak P, Charoenwat B, Paibool W, Laoaroon ์. Asparaginase with Thrombotic Complications in Pediatric Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. SRIMEDJ [Internet]. 2022 Aug. 30 [cited 2023 Jan. 30];37(4):313-22. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/254356
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