Pharmacokinetics of very prolonged Erwinia asparaginase use in relation to AAAs. Serum Erwinia asparaginase activity (A) and serum AAAs (B) against Erwinia asparaginase (Erwinia-AAAs) over time. Serum Erwinia asparaginase activity levels of patients without Erwinia-AAAs (C) and with Erwinia-AAAs (D) (mean ± SEM). Dashed lines in panels A, C, and D indicate Erwinia asparaginase activity level of 100 U/L. The dashed line in panel B indicates samples defined as positive for Erwinia-AAAs if the OD was >1.96 standard deviations above the negative control processed mean (using Westgard rules).²⁰