Purpose: Asparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E. coli typically more accessible in low- and middle-income countries (LMICs). Short shelf lives, intermittent availability, and concern for substandard formulations in LMICs have created a need for proactive ASN demand estimates.
Methods: We adapted FORxECAST, a pediatric cancer drug forecasting model, to focus on ASN for pediatric ALL. The model is adaptable to user data and defaults to best available public data where local data are unavailable. We forecast ASN quantity and cost in three case study countries for four scenarios using two regimens-base regimen (BR) and intensified regimen (IR)-outlining how quantity and costs vary on the basis of ASN formulation, dose, and second-line availability.
Results: Native E. coli is cheaper than PEG for first-line treatment across all scenarios. Regimen intensification from BR to IR requires a substantially higher cost when PEG is used relative to native E. coli. The cost of treating ASN hypersensitivity with Erwinase for BR in Burundi, Ghana, and Turkmenistan is $19,660 in US dollars (USD), $24,800 USD, and $15,246 USD, respectively.
Conclusion: Treatment intensification requires a cost increase that should be accessible for most LMICs, but PEG utilization is substantially more costly, suggesting that prioritizing investment in intensifying treatment using native E. coli is the least costly approach to maximize treatment availability. Cost savings associated with native E. coli utilization may liberate funds for Erwinase procurement for patients with ASN hypersensitivity. Future analyses needed include an evaluation of costs associated with preventing abandonment due to compliance complexity with native E. coli given increased administration frequency compared with PEG.
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http://dx.doi.org/10.1200/GO-24-00444 | DOI Listing |
JCO Glob Oncol
January 2025
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
Purpose: Asparaginase (ASN) is a critical component of pediatric ALL protocols. Until recently, ASN was available in three formulations: native Escherichia coli, PEGylated E. coli (PEG), and Erwinase, with native E.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin 14195, Germany.
Mucus is a complex hydrogel that acts as a defensive and protective barrier in various parts of the human body. The rise in the level of viral infections has underscored the importance of advancing research into mucus-mimicking hydrogels for the efficient design of antiviral agents. Herein, we demonstrate the gram-scale synthesis of biocompatible, lignin-based virus-binding inhibitors that reduce waste and ensure long-term availability.
View Article and Find Full Text PDFEnzyme Microb Technol
January 2025
Biotechnology Program, Department of Engineering Technology, Cullen College of Engineering, University of Houston, Houston, TX 77004, United States. Electronic address:
Meta-tyrosine (m-tyrosine), a nonproteinogenic amino acid, has shown significant potential for applications as an herbicide in agriculture and for various medical uses. However, the natural abundance of m-tyrosine is very low, limiting its widespread use. In this study, we successfully achieved microbial production of m-tyrosine by establishing the in vivo enzyme activity of phenylalanine 3-hydroxylase (PacX from Streptomyces coeruleoribudus) in E.
View Article and Find Full Text PDFSmall
January 2025
INM - Leibniz Institute for New Materials, Saarland University, Campus D2 2, 66123, Saarbrücken, Germany.
Engineered living materials (ELMs) made of bacteria in hydrogels have shown considerable promise for therapeutic applications through controlled and sustained release of complex biopharmaceuticals at low costs and with reduced wastage. While most therapeutic ELMs use E. coli due to its large genetic toolbox, most live biotherapeutic bacteria in development are lactic acid bacteria due to native health benefits they offer.
View Article and Find Full Text PDFBiotechnol Bioeng
January 2025
Department of Biosystems Engineering, Auburn University, Auburn, Alabama, USA.
Bacillus velezensis FZB42 is a prominent plant growth-promoting rhizobacterium and biocontrol agent known for producing a wide array of antimicrobial compounds. The capability to genetically manipulate this strain would facilitate understanding its metabolism and enhancing its sustainable agriculture applications. In this study, we report the first successful implementation of high-efficiency CRISPR-Cas9 genome editing in B.
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