Therapeutic drug monitoring of asparaginase in the ALL‐BFM 2000 protocol between 2000 and 2007

Schrey, Dominik; Borghorst, Stephan; Lanvers-Kaminsky, Claudia; Hempel, Georg; Gerß, Joachim; Möricke, Anja; Schrappe, Martin; Boos, Joachim

doi:10.1002/pbc.22417

Cited by 46 publications

(42 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to formation of neutralizing antibodies, especially during reinduction treatment, lower activities were expected. Thus, a confirmation of the predictive ability by an external data set including data of induction and reinduction phases as well as antibody data is required to extrapolate reliably outside induction phase [19,20]. External model validation will be performed in future PopPK analysis with data collected during induction and reinduction phases on a routine basis in the ALL-BFM treatment protocol.…”

Section: Assessment Of Bioequivalence Between a Recombinant Asnase Anmentioning

confidence: 98%

Population Pharmacokinetics of NativeEscherichia ColiAsparaginase

Borghorst

Pieters

Kuehnel

et al. 2012

Pediatric Hematology and Oncology

Self Cite

View full text Add to dashboard Cite

The main aim of this analysis was to characterize the population pharmacokinetics of native Escherichia coli asparaginase (ASNase medac) in pediatric patients with previously untreated acute lymphoblastic leukemia. Secondary objective was to give further evidence for bioequivalence between ASNase medac and a new recombinant ASNase preparation. The authors reanalyzed 233 plasma samples from 16 children treated according to the DCOG-ALL 10 protocol (5000 U/m(2) ASNase medac) using NONMEM. Subsequently, assessment of bioequivalence was performed by including the preparation as a categorical covariate into the PopPK model when analyzing data of both preparations (480 samples, 32 children). A linear 2-compartment model with first-order elimination sufficiently described ASNase medac pharmacokinetics. The parameters found were as follows: total body clearance 0.13 L/h ± 12.4% per 1.73 m(2), volume of distribution in the central compartment 4.11 L ± 12.3% per 70 kg, volume of distribution in the peripheral compartment 1.63 L per 70 kg and intercompartmental clearance 0.106 L/h (mean ± interindividual variability). A visual predictive check procedure and simulation of different dosages ASNase medac administered in the ALL-BFM protocol indicated adequate model performance. Assessment of bioequivalence provided a difference of about 14% in clearance of both preparations being too small to be considered as clinically relevant. A population pharmacokinetic model of ASNase medac in pediatric patients with previously untreated acute lymphoblastic leukemia was established. The model was able to describe asparaginase activity of different dosages in the ALL-BFM protocol and provides further evidence for bioequivalence between ASNase medac and a new recombinant asparaginase preparation.

show abstract

Section: Assessment Of Bioequivalence Between a Recombinant Asnase Anmentioning

confidence: 98%

Population Pharmacokinetics of NativeEscherichia ColiAsparaginase

Borghorst

Pieters

Kuehnel

et al. 2012

Pediatric Hematology and Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…[16][17][18][19] The half-life of plasma activity of native E. coli asparaginase following IV versus IM administration is 18.3 ± 2.8 h versus 41.7 ± 4.3 h, respectively. [16] The mean half-life of IV asparaginase Erwinia chrysanthemi is estimated at 7.51 h,[20] substantially shorter than the half-life following IM administration of asparaginase Erwinia chrysanthemi of 15.6 h ( Figure 1).…”

Section: Asparaginase Pharmacokineticsmentioning

confidence: 99%

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Burke

Rheingold

2016

Leukemia & Lymphoma

View full text Add to dashboard Cite

Asparaginase is a key component of therapy for acute lymphoblastic leukemia (ALL). Traditionally, asparaginase was administered intramuscularly but is now commonly given intravenously. Although intravenous administration is less painful, it can be challenging to differentiate hypersensitivity versus infusion-related reactions. The ability to distinguish between asparaginase-mediated reactions is critical to ensure optimal asparaginase treatment. In this paper, we will review the differences in pharmacokinetics and toxicities, when asparaginase is administered intravenously versus intramuscularly in pediatric patients with ALL. Differences between antibody-mediated hypersensitivity events and nonantibody-mediated infusion reactions will be addressed to assist practitioners in distinguishing between these clinically similar asparaginase-associated toxicities.ARTICLE HISTORY

show abstract

“…This protein was one of the first to be modified with mPEG because of its propensity to cause severe hypersensitivity reactions (up to 20-30% of patients) 13 or suffer from 'silent inactivation' by the neutralizing or opsonizing antibodies 14,15 . Modification of ASNase with mPEG in part overcomes these problems 16 , however, a key problem is that antibody responses against mPEG-ASNase continue to occur in B18% of patients [17][18][19] .…”

mentioning

confidence: 99%

Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo

et al. 2014

View full text Add to dashboard Cite

In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.

show abstract

Therapeutic drug monitoring of asparaginase in the ALL‐BFM 2000 protocol between 2000 and 2007

Abstract: The reduced dose of 5,000 U/m2 E. coli ASNase for induction treatment succeeded to achieve an activity level above 100 U/L in more than 90% of all samples. They confirm that dose reduction is reasonable and provide the basis for future treatment strategies employing ASNase.

Cited by 46 publications

References 24 publications

Population Pharmacokinetics of NativeEscherichia ColiAsparaginase

Population Pharmacokinetics of NativeEscherichia ColiAsparaginase

Differentiating hypersensitivity versus infusion-related reactions in pediatric patients receiving intravenous asparaginase therapy for acute lymphoblastic leukemia

Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo

Contact Info

Product

Resources

About