Abrar Mohammed Amira, Abdela Fozia, Tasamma Abel Tenaw, Shewangizaw Yemisrach Kifle, Weldeamanuel Mahlet Tsige
Department of Internal Medicine, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Cancer Rep (Hoboken). 2025 Mar;8(3):e70153. doi: 10.1002/cnr2.70153.
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.
L-天冬酰胺酶是急性淋巴细胞白血病（ALL）治疗的重要组成部分。然而，它与血栓形成风险增加相关，这反过来又增加了发病和死亡风险，并且对白血病相关结局产生负面影响。
评估2020年11月至2023年11月在蒂库尔·安贝萨专科医院（TASH）接受含L-天冬酰胺酶方案治疗的ALL患者中血栓事件的发生率及其相关因素。
在TASH进行了一项单中心回顾性横断面研究。共有152例在2020年11月至2023年11月期间接受含L-天冬酰胺酶方案治疗或正在接受该方案治疗的ALL患者纳入研究。数据从患者的病历中收集。数据录入并使用SPSS 26版进行分析，采用卡方检验评估自变量与因变量的关联。二元和多元逻辑回归分析用于确定因变量和自变量之间是否存在显著相关性，p值为0.25的变量纳入多元分析。对于多元分析，p值<0.05被认为具有统计学意义。
参与者的中位年龄为22.5岁（四分位间距18，30.8），其中59.9%为男性。大多数（84.2%）患者接受了儿科启发的ALL CALGB10403方案治疗。11.2%的患者发生了有记录的血栓事件。所有事件均为静脉血栓，脑静脉血栓形成是最常见的部位（41.2%）。44.4%的血栓形成发生在缓解诱导期。在多元逻辑回归分析中，年龄≥40岁以及达到完全缓解（CR）的时间>4周（年龄≥40岁，p = 0.019；调整优势比[AOR] 10.4，95%置信区间[CI]=1.47 - 75.0；达到CR的时间>04周，p = 0.037；AOR 4.8，95% CI = 1.10 - 20.72）与血栓形成风险增加显著相关。发生血栓的患者死亡率与未发生血栓的患者相比无统计学显著差异（47%对41.4%，p = 0.618）。血栓形成患者中约三分之一（29.4%）的死亡是血栓事件的直接影响。
本研究表明，在我们这样资源有限的环境中，L-天冬酰胺酶相关血栓形成的风险与世界其他地区先前的报告相当，但直接归因于血栓形成的死亡率明显更高。40岁以上的年龄和达到CR的时间较长是血栓形成风险较高的独立预测因素。未来的前瞻性研究需要探讨其促成因素以及预防和治疗策略。
