Schmidt Madalina-Petronela, Ivanov Anca-Viorica, Coriu Daniel, Miron Ingrith-Crenguta
Department Hemato-Oncology, "Sf. Maria" Children's Hospital, 700309 Iasi, Romania.
Department Mother and Child Care, "Grigore T Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
J Clin Med. 2021 Sep 26;10(19):4419. doi: 10.3390/jcm10194419.
Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children's Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1-11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis ( = 0.015) and hypertriglyceridemia ( = 0.043) and a lower risk of clinical hypersensitivity ( = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.
天冬酰胺酶是小儿急性淋巴细胞白血病（ALL）化疗的基本组成部分，在提高该疾病的长期生存率方面发挥了关键作用。这项回顾性研究的目的是阐明ALL儿童和青少年中天冬酰胺酶相关的毒性特征，分析每种毒性类型对长期预后的影响，并确定风险因素。我们分析了2010年至2019年在雅西圣玛丽亚儿童医院确诊为ALL并按照包含天冬酰胺酶的化疗方案进行治疗的165例患者的病历。中位随访时间为5年（0.1 - 11.5年）。将具有特定毒性类型的患者组与无毒性的患者组进行比较。我们发现天冬酰胺酶相关毒性的发生率如下：临床超敏反应24.1%，肝毒性19.4%，高甘油三酯血症6.7%，高血糖4.2%，骨坏死3.7%，胰腺炎3%，血栓形成2.4%，脑血栓形成1.2%。总体而言，82例患者（49.7%）至少有一种与天冬酰胺酶相关的毒性。没有一种毒性类型对总生存期或无事件生存期有显著影响。年龄大于14岁与骨坏死风险较高（P = 0.015）、高甘油三酯血症风险较高（P = 0.043）以及临床超敏反应风险较低（P = 0.04）相关。天冬酰胺酶相关毒性很常见且特征多样，其早期检测对于实现有效和适当的管理很重要。
