Prevalence and Risk Factors of L-Asparaginase-Related Thrombosis Among Acute Lymphoblastic Lymphoma Patients in a...

L-asparaginase is an important component of acute lymphoblastic leukemia (ALL) treatment. However, it is associated with an increased risk of thrombosis which in turn increases the risk of morbidity and mortality and also poses a negative effect on leukemia-related outcomes.

To assess the prevalence of thrombotic events and their associated factors in patients with ALL treated with L-asparaginase-containing regimens in Tikur Anbessa Specialized Hospital (TASH) from November 2020 to November 2023.

A single-center retrospective cross-sectional study was conducted at TASH. A total of 152 ALL patients who have been treated or were on treatment with L-asparaginase-containing regimens from November 2020 to November 2023 were included in the study. Data were collected from the patient's medical records. Data were entered and analyzed with SPSS version 26, and a chi-square test was used to assess the association of independent variables with the dependent variable. Bivariate and multivariate logistic regression analyses were used to determine the presence of significant correlation between dependent and independent variables and those with p-value of 0.25 were included in the multivariate analysis. For multivariate analysis a p-value < 0.05 was considered as statistically significant.

The median age of the participants was 22.5 years (IQR 18, 30.8), and 59.9% of them were male. The majority (84.2%) of patients were treated with pediatric-inspired ALL CALGB10403 protocol. Eleven point two percent of the patients developed a documented thrombotic event. All of the events were venous and, cerebral venous thrombosis was the most common site (41.2%). Thrombosis occurred during remission induction in 44.4%. On multivariate logistic regression analysis, age ≥ 40 years and longer time to achieve complete remission (CR) of > 4 weeks (Age ≥ 40 years, p = 0.019; adjusted odds ratio [AOR] 10.4, 95% confidence interval [CI] = 1.47-75.0 and, time to achieve CR > 04 weeks p = 0.037; AOR 4.8, 95% CI = 1.10-20.72) were significantly associated with increased risk of thrombosis. Patients who developed thrombosis had a statistically non-significant higher rate of mortality compared with those without thrombosis (47% vs. 41.4%, p = 0.618). Around a third (29.4%) of the deaths in the patients with thrombosis were direct effects of the thrombotic event.

This study showed that the risk of L-asparaginase-associated thrombosis in resource-limited settings like ours is comparable with previous reports from other parts of the world, but the mortality directly attributed to thrombosis is remarkably higher. Older age above 40 years and longer time to achieve CR are independent predictors of higher thrombosis risk. Future prospective studies need to look into the contributing factors, and preventive and treatment strategies.