1. Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia
by Dan Douer, Henry Yampolsky, Lewis J. Cohen, Kristy Watkins, Alexandra M. Levine, Antonia P. Periclou, and Vassilios I. Avramis
Blood
Volume 109(7):
April 1, 2007
©2007 by American Society of Hematology

2. NONMEM posthoc model of serum asparaginase enzymatic activity.
NONMEM posthoc model of serum asparaginase enzymatic activity. The data are from 23 adult patients who had 2 or more serum specimens after a single intravenous dose (2000 IU/m2) of pegaspargase. Each color indicates an individual patient, showing the variability between patients. Several patients had enzymatic activity of 0.2 IU/mL or greater on day 28. The NONMEM posthoc (best fit) model is shown in yellow circles demonstrating T1/2 = 7 days (95% CI, ) and volume of distribution = 2.43 L/m2, which is equal to plasma volume in adults.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology

3. Serum asparaginase enzymatic activity.
Serum asparaginase enzymatic activity. The results are from 19 patients who had 4 or more serum specimens after a single intravenous dose (2000 IU/m2) of pegaspargase over a period of 28 days. The results are depicted as the mean ± SD activity at the nearest time point to 7, 14, 21, and 28 days, respectively, after a single intravenous dose (2000/ IU/m2) of pegaspargase.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology

4. Serum asparagine concentrations representing asparagine deamination.
Serum asparagine concentrations representing asparagine deamination. The results are from 19 patients who had 4 or more serum specimens after a single intravenous dose (2000 IU/m2) of pegaspargase. The results are expressed as the mean ± SD. ASN indicates asparagine.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology

5. The relationship between asparaginase enzymatic activity of the pegaspargase and its substrate (asparagine).
The relationship between asparaginase enzymatic activity of the pegaspargase and its substrate (asparagine). The results are shown as a sigmoid pharmacodynamic relationship between the population mean of deaminated asparagine levels expressed as a percentage of pretreatment controls versus log10 of asparaginase enzymatic activity. The sigmoid relationship is of the third order of regression, as it is the upper portion of the sigmoid fit according to the Michelis-Menten reaction. Of note is that the time does not appear in the figure since it is embedded in the PPK of asparaginase enzymatic activity, which was obtained from Figure 2. Minimal enzymatic activity of 0.2 IU/mL was needed for optimal asparagine deamination of 90% compared with the baseline. Horizontal line indicates 90% of asparagine depletion below pretreatment levels; vertical line, 0.2 IU/mL of asparaginase activity; and ASN, asparagine.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology

6. Serum antithrombin activity.
Serum antithrombin activity. The results are from 11 patients who had 2 or more serum specimens taken after a single intravenous dose of pegaspargase administration (2000 IU/m2). Day 0 indicates prior to pegaspargase. Each color indicates an individual patient. The results are represented as a percentage of normal control plasma.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology

7. Overall survival and relapse-free survival (RFS).
Overall survival and relapse-free survival (RFS). The median follow-up was only 36 months as the study was conducted between 1995 and1999; since then, several patients were lost to follow-up and were censored at the time of last follow-up.
Dan Douer et al. Blood 2007;109:
©2007 by American Society of Hematology