Department of Pharmacy, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820980113. doi: 10.1177/1533033820980113.
This study aimed to investigate the correlation of L-asparaginase (L-asp) activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia (ALL) patients who underwent polyethylene glycol-conjugated L-asp (PEG-asp)-contained treatment.
Plasma samples were collected from 91 pediatric ALL patients who underwent PEG-asp-contained treatment on the 7th day after drug administration. Plasma L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level were detected. Meanwhile, AEs related to PEG-asp administration were recorded.
AEs occurred in 13 (14.3%) patients, among which 7 (7.7%) patients had anaphylaxis, while another 6 patients had non-anaphylaxis AEs (including 4 (4.4%) patients who had acute pancreatitis, 1 (1.1%) patient who had abdominal pain and diarrhea, as well as 1 (1.1%) patient who had nausea and vomiting). L-asp activity was decreased, while asparagine and glutamine levels were increased in patients with AEs compared to patients without AEs, and ROC curves showed that they were correlated with higher AEs risk. Notably, further analyses revealed that L-asp activity, anti-L-asp antibody, asparagine and glutamine levels were highly correlated with anaphylaxis risk, but they were not associated with the risk of non-anaphylactic AEs.
The measurement of L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level might assist the prevention of anaphylaxis-related AEs in pediatric ALL patients who underwent PEG-asp-contained treatment.
本研究旨在探讨 L-天冬酰胺酶(L-asp)活性、抗 L-asp 抗体、天冬酰胺和谷氨酰胺水平与接受聚乙二醇化 L-天冬酰胺酶(PEG-asp)治疗的儿童急性淋巴细胞白血病(ALL)患者发生不良事件(AEs),尤其是过敏反应风险的相关性。
收集 91 例接受 PEG-asp 治疗的儿童 ALL 患者在给药后第 7 天的血浆样本。检测血浆 L-asp 活性、抗 L-asp 抗体水平、天冬酰胺水平和谷氨酰胺水平,并记录与 PEG-asp 给药相关的 AEs。
13 例(14.3%)患者出现 AEs,其中 7 例(7.7%)患者发生过敏反应,另外 6 例患者发生非过敏反应 AEs(包括 4 例(4.4%)患者发生急性胰腺炎,1 例(1.1%)患者出现腹痛腹泻,1 例(1.1%)患者出现恶心呕吐)。与无 AEs 的患者相比,发生 AEs 的患者的 L-asp 活性降低,天冬酰胺和谷氨酰胺水平升高,ROC 曲线显示它们与更高的 AEs 风险相关。值得注意的是,进一步分析表明,L-asp 活性、抗 L-asp 抗体、天冬酰胺和谷氨酰胺水平与过敏反应风险高度相关,但与非过敏反应 AEs 风险无关。
测定 L-asp 活性、抗 L-asp 抗体水平、天冬酰胺水平和谷氨酰胺水平可能有助于预防接受 PEG-asp 治疗的儿童 ALL 患者发生过敏反应相关的 AEs。