{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T03:20:22Z","timestamp":1764645622994,"version":"3.41.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n            <jats:title>Background and Methods:<\/jats:title>\n            <jats:p>The present review aims to evaluate the current state-of-the-art dosing regimens of high-dose (HD) and intrathecal methotrexate (MTX) using therapeutic drug monitoring (TDM) to optimize its therapeutic response and minimize associated toxicity, particularly in the central nervous system (CNS).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>MTX is administered systemically in a HD regimen (&gt;1 g\/m<jats:sup>2<\/jats:sup>) for the treatment of various hematological neoplasms. HD-MTX treatment becomes complicated by marked interindividual drug elimination variability. TDM is specified to manage this high variability. Approximately 3%\u20137% of adults with acute lymphoblastic leukemia are diagnosed with CNS involvement, and the incidence of CNS relapse in patients, despite receiving prophylaxis, ranges from 5% to 10%. HD-MTX penetrates the blood\u2013brain barrier and can be administered intrathecally, making this drug an important component of chemotherapy regimens for patients with hematologic malignancies involving the CNS or those at high risk of CNS relapse.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The major evidence found was that an MTX area under the curve target between 1000 and 1100 \u03bcmol hour<jats:sup>\u22121<\/jats:sup> L is associated with better clinical outcomes. However, there seems to be a clinical gap in the prospective validation of HD and IT MTX management to optimize clinical outcomes and minimize toxicity, using the relationship between exposure level (area under the curve MTX) and optimal response to MTX, at systemic and CNS exposure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000001022","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T08:00:28Z","timestamp":1660636828000},"page":"287-292","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Optimum Methotrexate Exposure in Patients With Suspected or Confirmed CNS Invasive Hematological Malignancies: A Systematic Critical Review"],"prefix":"10.1097","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1635-8811","authenticated-orcid":false,"given":"Monteiro Joaquim","family":"Faria","sequence":"first","affiliation":[{"name":"Servi\u00e7o de Hematologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro;"},{"name":"ToxRun\u2014Toxicology Research Unit, Avenida Central de Gandra, Gandra Paredes;"}]},{"given":"Damas","family":"Rita","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro;"}]},{"given":"Bergantim","family":"Rui","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Hematologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, Alameda Prof. Hern\u00e2ni Monteiro;"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto; and"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology of the University of Porto, Porto, 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