{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:20:32Z","timestamp":1789017632952,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T00:00:00Z","timestamp":1414627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H14-Koka(Gan)-031"],"award-info":[{"award-number":["H14-Koka(Gan)-031"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H15-Koka(Gan)-024"],"award-info":[{"award-number":["H15-Koka(Gan)-024"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H16-GanRinsho-004"],"award-info":[{"award-number":["H16-GanRinsho-004"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H17-GanRinsho-004"],"award-info":[{"award-number":["H17-GanRinsho-004"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H20-GanRinsho-Ippan-017"],"award-info":[{"award-number":["H20-GanRinsho-Ippan-017"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H23-GanRinsho-Ippan-014"],"award-info":[{"award-number":["H23-GanRinsho-Ippan-014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Plasma monitoring of Methotrexate (MTX) levels is a standard approach to predict MTX\u2010related toxicities in a high\u2010dose (HD) MTX monotherapy for childhood acute lymphoblastic leukemia. However, it is uncertain whether plasma MTX levels can predict MTX\u2010related toxicity in the HDMTX plus additional chemotherapy for childhood B\u2010cell nonHodgkin lymphoma (B\u2010NHL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>To statistically analyze the relationship between MTX pharmacokinetic parameters and MTX\u2010related toxicities, we collected data from patients with delayed MTX elimination (\u22651\u2009\u00b5M at 48\u2009hr and\/or \u22650.5\u2009\u00b5M at 72\u2009hr) in the Japanese Pediatric Leukemia\/Lymphoma Study Group (JPLSG) BNHL 03 study. Blood MTX levels were measured at 24, 48, and 72\u2009hr after 3 or 5\u2009g\/m<jats:sup>2<\/jats:sup> HD\u2010MTX administration for 24\u2009hr.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three hundred and four patients received 2\u20134 courses of the HDMTX plus additional chemotherapy, and delayed MTX elimination was observed in 165 courses of 127 patients. In those, nephrotoxicity was significantly correlated with plasma MTX levels for each patient (<jats:italic>P<\/jats:italic>\u2009=\u20090.03), and also for each course (<jats:italic>P<\/jats:italic>\u2009=\u20090.009), but no other toxicities were correlated. Another analysis according to HDMTX courses showed no significant correlation between the first high plasma MTX levels and subsequent MTX levels in later course. It also showed that incidence of liver and gastrointestinal toxicities was most frequent in the first HDMTX course, and then sharply decreased in later courses (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that plasma MTX level is not a reliable predictor for adverse events except for nephrotoxicity in multiple HDMTX therapy courses in childhood B\u2010NHL. Pediatr Blood Cancer 2015;62:279\u2013284. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25305","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T16:02:20Z","timestamp":1414684940000},"page":"279-284","source":"Crossref","is-referenced-by-count":29,"title":["Statistical analysis of relation between plasma methotrexate concentration and toxicity in high\u2010dose methotrexate therapy of childhood nonHodgkin lymphoma"],"prefix":"10.1002","volume":"62","author":[{"given":"Masahito","family":"Tsurusawa","sequence":"first","affiliation":[{"name":"The Advanced Medical Research Center Aichi Medical University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Gosho","sequence":"additional","affiliation":[{"name":"The Advanced Medical Research Center Aichi Medical University Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Pediatric Oncology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University Hospital Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shosuke","family":"Sunami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Japanese Red Cross Narita Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Sapporo Hokuyu Hospital Sapporo 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Saitama Children's Medical Center Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Takimoto","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichiro","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Department of Pathology National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Horibe","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the lymphoma committee of the Japanese Pediatric Leukemia\/lymphoma Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,30]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3294","article-title":"Improved treatment results in childhood B\u2010cell neoplasms with tailored intensification of therapy: Reports of the Berlin\u2013Frankfurt\u2013M\u00fcnster 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