{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:58:50Z","timestamp":1769158730016,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:sc>l<\/jats:sc>\u2010Asparaginase hydrolyzes <jats:sc>l<\/jats:sc>\u2010asparagine and not its enantiomer <jats:sc>d<\/jats:sc>\u2010asparagine. Unlike <jats:sc>l<\/jats:sc>\u2010asparagine, <jats:sc>d<\/jats:sc>\u2010asparagine is nonessential for the survival of acute lymphoblastic leukemia (ALL) cells. Studies showed that serum asparagine is depleted below 0.5 \u03bcM in \u226596% of the patients during pegylated <jats:italic>Escherichia coli<\/jats:italic> <jats:sc>l<\/jats:sc>\u2010asparaginase (PEGasparaginase) treatment; however, cerebrospinal fluid (CSF) asparagine levels are depleted in only 20%\u201330% of the patients. Thus far, studies only reported the total CSF asparagine (sum of <jats:sc>d<\/jats:sc>\u2010 and <jats:sc>l<\/jats:sc>\u2010asparagine) concentrations. Data on the pharmacological goal, which is <jats:sc>l<\/jats:sc>\u2010asparagine depletion, are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Therefore, we studied this in 30 patients (95 samples) with newly diagnosed ALL. They received two doses of PEGasparaginase on day 4 and 18 in induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median age at diagnosis was 5.7 years (range 1.5\u201317.1 years). <jats:sc>d<\/jats:sc>\u2010Asparagine and <jats:sc>l<\/jats:sc>\u2010asparagine concentrations (median (range)) before PEGasparaginase treatment were 0.038 (0.0\u20130.103) \u03bcM and 6.1 (1.82\u201311.5) \u03bcM, respectively. CSF <jats:sc>l<\/jats:sc>\u2010asparagine concentrations were reduced by 85% (76%\u2013100%) and approximately one\u2010third of the patients (32%) had CSF <jats:sc>l<\/jats:sc>\u2010asparagine depletion below 0.5 \u03bcM 11 days after the second PEGasparaginase dose administration. CSF <jats:sc>d<\/jats:sc>\u2010asparagine and <jats:sc>l<\/jats:sc>\u2010glutamine levels remained stable before and after administration of PEGasparaginase. The percentage of <jats:sc>d<\/jats:sc>\u2010asparagine as a fraction of total asparagine (sum of <jats:sc>d<\/jats:sc>\u2010 and <jats:sc>l<\/jats:sc>\u2010asparagine) was 0.62% before and 4.5% after PEGasparaginase treatment. No correlation was found between higher serum PEGasparaginase activity and CSF <jats:sc>l<\/jats:sc>\u2010asparagine concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:sc>l<\/jats:sc>\u2010Asparagine is not a better parameter than total asparagine in CSF due to the negligible amount of <jats:sc>d<\/jats:sc>\u2010asparagine in the CSF before and after PEGasparaginase treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29865","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T20:30:12Z","timestamp":1658867412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Depletion of <scp>d<\/scp>\u2010 and <scp>l<\/scp>\u2010asparagine in cerebrospinal fluid in acute lymphoblastic leukemia during PEGasparaginase therapy"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2816-2610","authenticated-orcid":false,"given":"Leiah J.","family":"Brigitha","sequence":"first","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob","family":"Pieters","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard A.","family":"Struys","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers Clinical Chemistry  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdellatif","family":"Bakkali","sequence":"additional","affiliation":[{"name":"Amsterdam University Medical Centers Clinical Chemistry  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5822-7668","authenticated-orcid":false,"given":"Inge M.","family":"van der Sluis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"5614","article-title":"Antitumor activity of DL\u2010threo\u2010beta\u2010fluoroasparagine against human leukemia cells in culture and L1210 cells in DBA mice","volume":"44","author":"Stern AM","year":"1984","journal-title":"Cancer 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