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R.Q.H. Kloos et al.
found the opposite: patients with a lower weight have a higher CL, requiring a higher starting dose of the drug.25 Shrey et al. studied the native E. coli asparaginase levels in different age groups and also showed lower asparaginase activity levels in younger patients, suggesting a higher CL in these patients.26 Thus, for a PEGylated form of asparag- inase, this does not seem to apply, which is also supported by a study of PEGylated interferon α-2b in children, which also shows that the CL increases with age.27
In our analysis, PEGasparaginase CL was not statistical- ly correlated with asparaginase-related toxicity. The corre- lation between toxicity and asparaginase activity levels was also studied in 382 pediatric patients treated accord- ing to the DCOG ALL-11 protocol. In these patients, PEGasparaginase treatment, as in the current cohort, was individualized based on asparaginase activity levels, resulting in much lower trough levels compared to patients who were treated according to the DCOG ALL-
A
B
Figure 3. Visual predictive check. (A) and (B) show the visual predictive checks of the index and validation dataset, respectively. The observations and their corre- sponding median and 95% Confidence Intervals (CI) are indicated by the points, and the solid and dashed red lines. In both graphs, these lines fall within the 95% CI of the median and 95% CI (red and blue shaded areas) as obtained by simulation.
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haematologica | 2021; 106(5)