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Background <p>The relationship between early post-transplantation cyclosporine A (CsA) trough concentrations and the occurrence of acute graft-versus-host disease (aGVHD) was explored in 185 pediatric patients diagnosed with severe β-Thalassemia who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p> Methods <p>The time-weighted average (TWA) method was utilized to calculate the average of all CsA trough concentrations taken before aGVHD or within 30 days post-transplantation.</p> Results <p>It was found that TWA CsA trough exposure early post-transplantation was associated with grade II-IV aGVHD and grade III-IV aGVHD in univariate analysis and the Kaplan-Meier curves. After adjusting for potential confounders, multivariate analysis indicated that TWA CsA ≥ 150&#xa0;µg/L was correlated with a reduced risk of grade II-IV aGVHD (<i>P</i> = 0.003; HR = 0.338; 95%CI, 0.167–0.685) and grade III-IV aGVHD (<i>P</i> = 0.012; HR = 0.203; 95%CI, 0.058–0.708). Notably, the optimal threshold concentration of CsA for preventing the onset of aGVHD in pediatric patients, was found TWA CsA ≥ 131&#xa0;µg/L was associated with a lower risk of grade II-IV aGVHD (<i>P</i> &lt; 0.001; HR = 0.271; 95%CI, 0.145–0.507, while a TWA CsA ≥ 135&#xa0;µg/L was correlated with a lower risk of grade III-IV aGVHD (<i>P</i> = 0.002; HR = 0.190; 95%CI, 0.066–0.545). Upon comparing models with different thresholds, no significant improvement in performance was observed for models that incorporated relatively higher thresholds.</p> Conclusions <p>This research indicates the initial CsA trough concentration post-transplantation significantly influences the development of aGVHD and children with severe β-Thalassemia undergoing allo-HSCT may not require CsA trough threshold concentrations as high as those required for adults.</p>

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Lowering cyclosporine trough concentration threshold effectively mitigates acute graft-versus-host disease in children with severe β-Thalassemia post hematopoietic stem cell transplantation

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Zhuolin Yang,
  • Xianggui Wang,
  • Xiaojing Wang,
  • Wenjiao Ding,
  • Yiyu Zhang,
  • Qingling Gu,
  • Wenqing Wang,
  • Yousi Miao,
  • Ping Xie,
  • Min Huang,
  • Hua Jiang,
  • Xiaolan Mo,
  • Jiali Li

摘要

Background

The relationship between early post-transplantation cyclosporine A (CsA) trough concentrations and the occurrence of acute graft-versus-host disease (aGVHD) was explored in 185 pediatric patients diagnosed with severe β-Thalassemia who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods

The time-weighted average (TWA) method was utilized to calculate the average of all CsA trough concentrations taken before aGVHD or within 30 days post-transplantation.

Results

It was found that TWA CsA trough exposure early post-transplantation was associated with grade II-IV aGVHD and grade III-IV aGVHD in univariate analysis and the Kaplan-Meier curves. After adjusting for potential confounders, multivariate analysis indicated that TWA CsA ≥ 150 µg/L was correlated with a reduced risk of grade II-IV aGVHD (P = 0.003; HR = 0.338; 95%CI, 0.167–0.685) and grade III-IV aGVHD (P = 0.012; HR = 0.203; 95%CI, 0.058–0.708). Notably, the optimal threshold concentration of CsA for preventing the onset of aGVHD in pediatric patients, was found TWA CsA ≥ 131 µg/L was associated with a lower risk of grade II-IV aGVHD (P < 0.001; HR = 0.271; 95%CI, 0.145–0.507, while a TWA CsA ≥ 135 µg/L was correlated with a lower risk of grade III-IV aGVHD (P = 0.002; HR = 0.190; 95%CI, 0.066–0.545). Upon comparing models with different thresholds, no significant improvement in performance was observed for models that incorporated relatively higher thresholds.

Conclusions

This research indicates the initial CsA trough concentration post-transplantation significantly influences the development of aGVHD and children with severe β-Thalassemia undergoing allo-HSCT may not require CsA trough threshold concentrations as high as those required for adults.