Background Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy in India, with survival rates (60%–70%) significantly lower than in high-income countries (85%–90%). Asparaginase, a cornerstone of ALL therapy, has a narrow therapeutic window with substantial interpatient pharmacokinetic variability. However, therapeutic drug monitoring is rarely performed in resource-limited settings. Methods The prospective pilot study assessed serum asparaginase activity during induction therapy in Indian children with high-risk B-cell ALL. Of 30 enrolled patients, nine high-risk cases (aged 1–12 years) received L-asparaginase according to the modified ICiCLe protocol. Serum asparaginase activity was measured using a spectrophotometric assay at pre-dose (trough) and 24-h post-dose (peak) time points. Treatment-related toxicities were monitored using standardized criteria. Results Among the nine high-risk patients, five completed inductions, three died from treatment-related complications, and one was transferred. All evaluable patients ( n = 5) had subtherapeutic trough asparaginase activity (0.5 IU/mL; target ≥0.5 IU/mL). Peak levels showed marked interpatient variability (range: 0.52–1.97 IU/mL; median: 1.15 IU/mL). Higher enzyme activity correlated with biochemical toxicities: hepatotoxicity (5/5), elevated blood urea nitrogen (4/5), hypertriglyceridemia (3/5), and subclinical pancreatitis (2/5). Conclusion This pilot study demonstrates consistently subtherapeutic trough asparaginase levels in a small cohort of Indian children with high-risk ALL, suggesting potential inadequate drug exposure during induction therapy. These findings highlight the potential role of therapeutic drug monitoring in optimizing dosing and minimizing toxicity in resource-limited settings. Larger, adequately powered studies are required to validate these observations and establish population-specific pharmacokinetic parameters and dosing strategies.
Dhanda et al. (Thu,) studied this question.