{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:51:14Z","timestamp":1791532274129,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp;amp; Cancer"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>High\u2010dose methotrexate (HDMTX) can lead to toxicities including nephrotoxicity, myelosuppression, and mucositis. Glucarpidase is a recombinant bacterial enzyme that inactivates extracellular methotrexate (MTX). Prior studies suggest that glucarpidase doses &lt;50\u00a0units\/kg may effectively decrease serum MTX concentrations. The purpose of this study was to evaluate dose\u2010capping glucarpidase at 1000 units in pediatric and young adults patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      This retrospective, single\u2010center study (2013\u20132024) included glucarpidase administrations of 1000 units after HDMTX administration (doses greater than 500\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). Glucarpidase doses \u226550\u00a0units\/kg were excluded. The primary endpoint was the incidence of administrations achieving a clinically significant reduction (&gt;95% reduction) in serum MTX concentrations following dose\u2010capped glucarpidase, at first measurement by high\u2010performance liquid chromatography (HPLC). MTX\u2010related toxicities were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen glucarpidase administrations were included. The median age was 14.3 years and the median glucarpidase dose was 19.2\u00a0units\/kg. Twelve administrations (86%) had Grade 2\u20134 acute kidney injury (AKI) prior to glucarpidase. All 12 administrations with available HPLC data (100%) achieved a clinically significant reduction in serum MTX concentrations, with a median reduction of 99.5%. Among administrations with Grade 2\u20134 AKI, the median time to renal recovery was 6.9 days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Glucarpidase doses capped at 1000 units (&lt;50\u00a0units\/kg) were associated with clinically significant reductions in serum MTX concentrations. Reduced\u2010dose glucarpidase was generally well tolerated, with no unexpected safety concerns. While dose\u2010capping may be considered in select patients, further prospective, dose\u2010finding studies in humans are needed before employing this approach outside clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/1545-5017.70737","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:36:31Z","timestamp":1791531391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dose\u2010Capping Glucarpidase in Pediatric Patients for the Management of Delayed Clearance of High\u2010Dose Methotrexate"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7415-3488","authenticated-orcid":false,"given":"Christopher","family":"Phillips","sequence":"first","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Koehler","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4686-689X","authenticated-orcid":false,"given":"Gianna","family":"Galioto","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2017\u20100243"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1360"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.11\u20106\u2010694"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1507547"},{"key":"e_1_2_8_6_1","volume-title":"Voraxaze\u00ae (Glucarpidase Injection) [Package Insert]","year":"2022"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103565(24)39150\u20105"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024026211"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm\u20102024\u20100523"},{"key":"e_1_2_8_10_1","volume-title":"Application Number 125327Orig1s000. U.S. Food and Drug Administration","author":"International B. T. G.","year":"2012"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.12\u201011\u20101299"},{"key":"e_1_2_8_12_1","first-page":"322","article-title":"Reduced\u2010Dose Carboxypeptidase\u2010G2 Successfully Lowers Elevated Methotrexate Levels in an Adult With Acute Methotrexate\u2010Induced Renal Failure","volume":"11","author":"Trifilio S.","year":"2013","journal-title":"Clinical Advances in Hematology & Oncology"},{"key":"e_1_2_8_13_1","first-page":"1518","volume-title":"Comparable Efficacy with Varying Dosages of Glucarpidase in Pediatric Oncology Patients","author":"Scott J. R.","year":"2015"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2021.01.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010021\u201004361\u20108"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277\u2010026\u201006943\u2010z"},{"key":"e_1_2_8_17_1","unstructured":"ARK Diagnostics.ARK Methotrexate Assay Rev 11(ARK Diagnostics; 2025). Accessed June 16 2026."},{"key":"e_1_2_8_18_1","volume-title":"Methotrexate Post Glucarpidase, Serum","year":"2026"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1957"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.30506","article-title":"A Pooled Subgroup Analysis of Glucarpidase Treatment in 86 Pediatric, Adolescent, and Young Adult Patients Receiving High\u2010dose Methotrexate Therapy in Open\u2010Label Trials","volume":"27","author":"Janeway K. A.","year":"2023","journal-title":"Pediatric Blood Cancer"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197709222971203"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.22.00182"},{"key":"e_1_2_8_23_1","first-page":"432","article-title":"Delayed Elimination Concentrations of High\u2010Dose Methotrexate in Adults With Hematological Malignancies: To Standardize or Not? A Scoping Review","volume":"48","author":"T F.","year":"2025","journal-title":"Therapeutic Drug Monitoring"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102021\u2010151081"},{"key":"e_1_2_8_25_1","unstructured":"Centers for Disease Control and Prevention Adult BMI Categories. Accessed June 15 2026."},{"issue":"5","key":"e_1_2_8_26_1","first-page":"324","article-title":"Using a Lower Dose of Glucarpidase to Reduce Plasma Levels of Methotrexate","volume":"11","author":"Widemann B. 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