Hepatotoxicity from high-dose methotrexate in primary central nervous system lymphoma

被引:1
|
作者
Zhang, Joy C. [1 ]
Stotts, Matthew J. [2 ]
Horton, Bethany [3 ]
Schiff, David [4 ,5 ,6 ,7 ]
机构
[1] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA
[2] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA USA
[3] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA
[4] Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA
[5] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA
[6] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA USA
[7] Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22908 USA
关键词
common toxicity criteria; drug-induced liver injury; Fibrosis-4; score; hepatotoxicity; Liver enzyme tests; LIVER; HYPERTENSION; FIBROSIS; CHILDREN; DISEASE; RISK;
D O I
10.1093/nop/npad008
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background High-dose methotrexate (HDMTX) is a mainstay of primary central nervous system lymphoma (PCNSL) treatment. Transient hepatotoxicity from HDMTX has been characterized in pediatric patients but not in adults. We sought to characterize hepatotoxicity in adult PCNSL patients undergoing HDMTX treatment. Methods Retrospective study of 65 PCNSL patients treated at the University of Virginia from 02/01/2002 to 04/01/2020 was performed. Hepatotoxicity was defined using National Cancer Institute Common Toxicity Criteria (CTC) for adverse events, fifth version. High-grade hepatotoxicity was defined as a bilirubin or aminotransferase CTC grade of 3 or 4. Relationships between clinical factors and hepatotoxicity were assessed with logistic regression. Results Most patients (90.8%) had a rise of at least one aminotransferase CTC grade during HDMTX treatment. 46.2% had high-grade hepatotoxicity based on aminotransferase CTC grade. No patients developed high-grade bilirubin CTC grades during chemotherapy. Liver enzyme test values decreased to low CTC grade or normal in 93.8% of patients after the conclusion of HDMTX treatment without treatment regimen changes. Prior ALT elevation (P = .0120) was a statistically significant predictor of high-grade hepatotoxicity during treatment. Prior history of hypertension was associated with increased risk of toxic serum methotrexate levels during any cycle (P = .0036). Conclusions Hepatotoxicity develops in the majority of HDMTX-treated PCNSL patients. Transaminase values decreased to low or normal CTC grades in almost all patients after treatment, without modification of MTX dosage. Prior ALT elevation may predict patients' increased hepatotoxicity risk, and hypertension history may be a risk factor for delayed MTX excretion.
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收藏
页码:291 / 300
页数:10
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