Clinical Risk Factors for High-Dose Methotrexate-Induced Oral Mucositis Following Individualized Dosing

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-01 DOI:10.1002/cam4.70351

Zhongbo Hu, Andrea M. Escalera-Joy, Emily Ashcraft, Rushil Acharya, Sima Jeha, Cheng Cheng, Ching-Hon Pui

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Abstract

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.

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个体化给药后大剂量甲氨蝶呤诱发口腔黏膜炎的临床风险因素。

背景：在接受大剂量甲氨蝶呤（HDMTX）治疗的急性淋巴细胞白血病（ALL）患儿中，约有 20% 患有口腔黏膜炎，尽管已有管理策略。根据药代动力学和白血病风险调整的个性化 HDMTX 剂量降低了粘膜炎的发病率，但在 24 小时甲氨蝶呤水平相似的情况下仍会出现差异：这项回顾性研究调查了个体化甲氨蝶呤方案下口腔黏膜炎的风险因素。这项回顾性研究调查了个体化甲氨蝶呤方案下口腔黏膜炎的风险因素。研究分析了圣裘德儿童研究医院总计16例试验中≥2级口腔黏膜炎（CTCAE v4.0）患者的数据。1:1病例对照匹配法考虑了年龄、性别、风险分类、免疫表型和甲氨蝶呤疗程。统计分析采用 McNemar's、Bowker's 对称检验和 Wilcoxon 符号秩检验。在病例分析中确定了复发性粘膜炎的风险因素：发热、皮疹、AKI、甲氨蝶呤清除延迟和42 h甲氨蝶呤水平升高是HDMTX诱发口腔黏膜炎的主要危险因素。皮疹、发热和中性粒细胞减少是独立的预测因素，而女性性别和缺氧缺血性心肌梗死与复发性粘膜炎有关。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

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.