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Purpose <p>Voriconazole (VRC), a broad-spectrum antifungal agent, is commonly used for the treatment and prophylaxis of invasive fungal disease (IFD) in patients with hematologic malignancies following chemotherapy. However, its clinical application is often limited by central nervous system (CNS) toxicity. CNS toxicity was defined using the National Cancer Institute criteria, such as hallucinations and anxiety. The aim of this study was to identify risk factors associated with VRC-induced CNS toxicity and to determine the plasma trough concentration (C<sub>min</sub>) threshold.</p> Methods <p>This retrospective cohort study analyzed clinical data from 126 patients with hematologic malignancies who received VRC after chemotherapy and underwent therapeutic drug monitoring (TDM).</p> Results <p>The 126 patients, 30 (23.8%) developed CNS toxicity related to VRC. The median time to onset of CNS toxicity was 6 days following VRC initiation. VRC C<sub>min</sub> levels were significantly associated with an increased risk of CNS toxicity (odds ratio: 2.08; 95% confidence interval [CI]: 1.56–2.78, <i>p</i> &lt; 0.001 per 1&#xa0;mg/L increment on multivariate analysis). Receiver operating characteristic curve analysis identified a C<sub>min</sub> threshold of 4.79&#xa0;mg/L for predicting CNS toxicity, with an area under the curve of 0.89 (95% CI: 0.82–0.97; <i>P</i> &lt; 0.001) and sensitivities and specificities of 0.87 and 0.85, respectively.</p> Conclusion <p>Therefore, routine TDM is recommended for patients with hematologic malignancies receiving VRC to minimize the risk of CNS toxicity.</p>

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Trough concentration of voriconazole and its association with central nervous system toxicity in patients with hematologic malignancies: a retrospective cohort study

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Qinghua Zhang,
  • Junwei Chen,
  • Wenming Tan,
  • Weien Li,
  • Lirong Tan,
  • Xiuling Wen

摘要

Purpose

Voriconazole (VRC), a broad-spectrum antifungal agent, is commonly used for the treatment and prophylaxis of invasive fungal disease (IFD) in patients with hematologic malignancies following chemotherapy. However, its clinical application is often limited by central nervous system (CNS) toxicity. CNS toxicity was defined using the National Cancer Institute criteria, such as hallucinations and anxiety. The aim of this study was to identify risk factors associated with VRC-induced CNS toxicity and to determine the plasma trough concentration (Cmin) threshold.

Methods

This retrospective cohort study analyzed clinical data from 126 patients with hematologic malignancies who received VRC after chemotherapy and underwent therapeutic drug monitoring (TDM).

Results

The 126 patients, 30 (23.8%) developed CNS toxicity related to VRC. The median time to onset of CNS toxicity was 6 days following VRC initiation. VRC Cmin levels were significantly associated with an increased risk of CNS toxicity (odds ratio: 2.08; 95% confidence interval [CI]: 1.56–2.78, p < 0.001 per 1 mg/L increment on multivariate analysis). Receiver operating characteristic curve analysis identified a Cmin threshold of 4.79 mg/L for predicting CNS toxicity, with an area under the curve of 0.89 (95% CI: 0.82–0.97; P < 0.001) and sensitivities and specificities of 0.87 and 0.85, respectively.

Conclusion

Therefore, routine TDM is recommended for patients with hematologic malignancies receiving VRC to minimize the risk of CNS toxicity.