Asian Journal of Pediatric Research

Objective: To investigate the distribution characteristics of pegaspargase blood concentration at 7 days after administration in children with acute lymphoblastic leukemia (ALL) treated with pegaspargase, its correlation with common adverse reactions, screen the early warning thresholds for adverse reactions, and evaluate the clinical feasibility of single-time-point therapeutic drug monitoring (TDM). 

Methods: A single-center, prospective observational design was adopted, enrolling 65 children with ALL aged 1-18 years who all received a standardized chemotherapy regimen containing pegaspargase (dose: 2500 IU/m², intramuscular injection every 14 days). Peripheral blood was collected on the 7th day after the first administration, and pegaspargase blood concentration was detected by enzyme-linked immunosorbent assay (ELISA). Patients were divided into low, medium, and high concentration groups according to quartiles. Adverse reactions such as liver injury and coagulation abnormalities were evaluated with reference to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTC) Version 5.0. Early warning thresholds were screened by Spearman correlation analysis and receiver operating characteristic (ROC) curve. 

Results: A total of 60 valid samples were finally obtained. The blood concentration of pegaspargase at 7 days after administration showed a normal distribution, with a mean of (16.8±7.5) IU/L, a median of 15.9 IU/L, and an interquartile range of [10.3, 22.5] IU/L. Eighty percent of the children had a concentration ≥10 IU/L (the sufficient activity threshold recommended by the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG)). The incidence rates of liver injury (60.0%) and coagulation abnormalities (46.7%) in the high concentration group (>22.5 IU/L) were significantly higher than those in the low concentration group (13.3% and 6.7%) (P<0.05). The blood concentration was moderately positively correlated with ALT (r_s=0.426), AST (r_s=0.389), PT (r_s=0.365), and APTT (r_s=0.328) (P<0.01). The optimal early warning thresholds for grade ≥2 liver injury and coagulation abnormalities were 18.7 IU/L (AUC=0.836) and 20.3 IU/L (AUC=0.792), respectively. There was no significant correlation between blood concentration and hyperglycemia or allergic reactions (P>0.05). 

Conclusion: The ideal reference interval of pegaspargase blood concentration at 7 days after administration in Chinese children and adolescents with ALL is 10.3-22.5 IU/L, and 18.7 IU/L and 20.3 IU/L can be used as the early warning thresholds for liver injury and coagulation abnormalities, respectively. The single-time-point TDM scheme at 7 days after administration is convenient to operate and reliable in results, which can be used for clinical individualized medication guidance and reduce the risk of adverse reactions. These findings provide a localized basis for individualized medication and toxicity early warning of pegaspargase in Chinese pediatric ALL, and promote the clinical application of single-time-point TDM.