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

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). 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. 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. 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.