Zhongbo Hu, Andrea M. Escalera-Joy, Emily Ashcraft, Rushil Acharya, Sima Jeha, Cheng Cheng, Ching-Hon Pui
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A 1:1 case–control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (<i>p</i> = 0.0027), fever (<i>p</i> = 0.0016), neutropenic fever (<i>p</i> = 0.0008), lower absolute neutrophil count (<i>p</i> < 0.0001), acute kidney injury (AKI) (<i>p</i> = 0.0164), delayed methotrexate clearance (<i>p</i> = 0.0133), and higher 42-h methotrexate levels (<i>p</i> = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (<i>p</i> = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, <i>p</i> = 0.0016), fever (OR 2.8, <i>p</i> = 0.009), and neutropenia (OR 2.3, <i>p</i> = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, <i>p</i> = 0.015) and AKI (OR 3.819, <i>p</i> = 0.037) were associated with recurrent mucositis.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Fever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis.</p>\n </section>\n </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 21","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529650/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing\",\"authors\":\"Zhongbo Hu, Andrea M. Escalera-Joy, Emily Ashcraft, Rushil Acharya, Sima Jeha, Cheng Cheng, Ching-Hon Pui\",\"doi\":\"10.1002/cam4.70351\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Oral mucositis affects about 20% of children undergoing high-dose methotrexate (HDMTX) for acute lymphoblastic leukemia (ALL), despite existing management strategies. Personalized HDMTX dosing, adjusted by pharmacokinetics and leukemia risk, has reduced mucositis incidence, but variations still occur with similar 24-h methotrexate levels.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This retrospective study investigated risk factors for oral mucositis under individualized methotrexate protocols. Data from patients with ≥ Grade 2 oral mucositis (CTCAE v4.0) were analyzed from the St. Jude Children's Research Hospital total 16 trial. A 1:1 case–control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>The study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (<i>p</i> = 0.0027), fever (<i>p</i> = 0.0016), neutropenic fever (<i>p</i> = 0.0008), lower absolute neutrophil count (<i>p</i> < 0.0001), acute kidney injury (AKI) (<i>p</i> = 0.0164), delayed methotrexate clearance (<i>p</i> = 0.0133), and higher 42-h methotrexate levels (<i>p</i> = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (<i>p</i> = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, <i>p</i> = 0.0016), fever (OR 2.8, <i>p</i> = 0.009), and neutropenia (OR 2.3, <i>p</i> = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, <i>p</i> = 0.015) and AKI (OR 3.819, <i>p</i> = 0.037) were associated with recurrent mucositis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Fever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis.</p>\\n </section>\\n </div>\",\"PeriodicalId\":139,\"journal\":{\"name\":\"Cancer Medicine\",\"volume\":\"13 21\",\"pages\":\"\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529650/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70351\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cam4.70351","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing
Background
Oral mucositis affects about 20% of children undergoing high-dose methotrexate (HDMTX) for acute lymphoblastic leukemia (ALL), despite existing management strategies. Personalized HDMTX dosing, adjusted by pharmacokinetics and leukemia risk, has reduced mucositis incidence, but variations still occur with similar 24-h methotrexate levels.
Methods
This retrospective study investigated risk factors for oral mucositis under individualized methotrexate protocols. Data from patients with ≥ Grade 2 oral mucositis (CTCAE v4.0) were analyzed from the St. Jude Children's Research Hospital total 16 trial. A 1:1 case–control matching method considered age, sex, risk classification, immunophenotype, and methotrexate course. McNemar's, Bowker's symmetry, and Wilcoxon signed-rank tests were used for statistical analyses. Risk factors for recurrent mucositis were identified in a case-only analysis.
Results
The study found significant associations between methotrexate-induced mucositis and new-onset skin rashes (p = 0.0027), fever (p = 0.0016), neutropenic fever (p = 0.0008), lower absolute neutrophil count (p < 0.0001), acute kidney injury (AKI) (p = 0.0164), delayed methotrexate clearance (p = 0.0133), and higher 42-h methotrexate levels (p = 0.0179). In the standard/high-risk group, mercaptopurine dose was also linked to mucositis (p = 0.0495). Multivariable analysis showed that skin rashes (OR 6.5, p = 0.0016), fever (OR 2.8, p = 0.009), and neutropenia (OR 2.3, p = 0.0106) were independent risk factors for mucositis. Female sex (OR 7.12, p = 0.015) and AKI (OR 3.819, p = 0.037) were associated with recurrent mucositis.
Conclusions
Fever, skin rashes, AKI, delayed methotrexate clearance, and higher 42-h methotrexate levels were key risk factors for HDMTX-induced oral mucositis. Skin rashes, fever, and neutropenia were independent predictors, while female sex and AKI were linked to recurrent mucositis.
期刊介绍：
Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas:
Clinical Cancer Research
Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations
Cancer Biology:
Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery.
Cancer Prevention:
Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach.
Bioinformatics:
Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers.
Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.
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