{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:36Z","timestamp":1787013936029,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,4,5]],"date-time":"2014-04-05T00:00:00Z","timestamp":1396656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008363","name":"The Danish Cancer Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Danish Childhood Cancer Foundation"},{"name":"The M.L J\u00ef\u00bf\u00bdrgensen and Gunner Hansen Foundation"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,7]]},"abstract":"Summary<\/jats:title>\n \n L\u2010asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (\n ALL<\/jats:styled-content>\n ). Cerebrospinal fluid (\n CSF<\/jats:styled-content>\n ) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (\n CNS<\/jats:styled-content>\n ) and may play a role in\n CNS<\/jats:styled-content>\n \u2010directed anti\u2010leukaemia therapy. The objective of this study was to describe\n CSF<\/jats:styled-content>\n asparagine depletion during 30\u00a0weeks of pegylated asparaginase therapy, 1000\u00a0iu\/m\n 2<\/jats:sup>\n i.m. every second week, and to correlate\n CSF<\/jats:styled-content>\n asparagine concentration with serum\n L<\/jats:styled-content>\n \u2010asparaginase enzyme activity. Danish children (1\u201317\u00a0years) with\n ALL<\/jats:styled-content>\n , treated according to the\n N<\/jats:styled-content>\n ordic\n S<\/jats:styled-content>\n ociety of\n P<\/jats:styled-content>\n aediatric\n H<\/jats:styled-content>\n aematology and\n O<\/jats:styled-content>\n ncology\n ALL<\/jats:styled-content>\n 2008 protocol, standard and intermediate risk, were included.\n CSF<\/jats:styled-content>\n samples were obtained throughout\n L<\/jats:styled-content>\n \u2010asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median\n CSF<\/jats:styled-content>\n asparagine concentration decreased from a pre\u2010treatment level of 5\u00b73\u00a0\u03bcmol\/l to median levels \u22641\u00b75\u00a0\u03bcmol\/l. However, only 4\/31 patients (five samples) had\n CSF<\/jats:styled-content>\n asparagine concentrations below the limit of detection (0\u00b71\u00a0\u03bcmol\/l). In 11 patients, 24 paired same day serum and\n CSF<\/jats:styled-content>\n samples were obtained. A decrease in\n CSF<\/jats:styled-content>\n asparagine corresponded to serum enzyme activities above 50\u00a0iu\/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000\u00a0iu\/m\n 2<\/jats:sup>\n i.m. every second week effectively reduced\n CSF<\/jats:styled-content>\n asparagine levels.\n <\/jats:p>","DOI":"10.1111\/bjh.12865","type":"journal-article","created":{"date-parts":[[2014,4,5]],"date-time":"2014-04-05T02:28:08Z","timestamp":1396664888000},"page":"213-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"166","author":[{"given":"Louise T.","family":"Henriksen","sequence":"first","affiliation":[{"name":"Department of Paediatrics Aarhus University Hospital Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Nersting","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Medicine University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raheel A.","family":"Raja","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Medicine University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Frandsen","sequence":"additional","affiliation":[{"name":"Department of Paediatric and Adolescent Medicine University Hospital Rigshospitalet Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steen","family":"Rosth\u00f8j","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Aalborg University Hospital Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Schr\u00f8der","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Aarhus University Hospital Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte K.","family":"Albertsen","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Aarhus University Hospital Aarhus N Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Nordic Society of Paediatric Haematology and Oncology (NOPHO) group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.d01-2089.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002800100286"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1740925X11000093"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403143"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-395855"},{"key":"e_1_2_9_7_1","first-page":"4363","article-title":"In vitro and in vivo killing of acute lymphoblastic leukemia cells by L\u2010asparaginase","volume":"49","author":"Asselin B.L.","year":"1989","journal-title":"Cancer 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