Cyclosporine related adverse events in aplastic anemia patients treated with immunosuppressive therapy

Few studies have focused on cyclosporine-related adverse events (AEs) in aplastic anemia (AA) patients undergoing immunosuppressive therapy and receive cyclosporine maintenance.

We conducted a retrospective study to analyze the relationship between cyclosporine concentrations at different time points and AEs in AA patients who received cyclosporine maintenance. Cutoff values of cyclosporine concentrations for predicting every AE were defined by receiver operating characteristic (ROC) curves respectively.

A total of 382 patients were included. The most common AEs included hypertrichosis (72.3%), gingival hyperplasia (60.5%), hyperuricemia (62.6%), hyperlipidemia (47.0%), and elevated creatinine levels (39.9%). Patients presented with AEs were with higher C0 (trough) and C2 (peak) levels. Most of the values of C0 and C2 were in the ranges of 200-250 μg/L and 700-1000 μg/L, respectively. Patients with C0 higher than 250 μg/L or C2 higher than 1000 μg/L were more likely to develop AEs. Response rate was not associated with cyclosporine concentrations, but C0 levels below 150 μg/L or C2 levels below 500 μg/L showed lower response trend. Based on these findings, we propose a therapeutic range of 150-250 μg/L for C0 and 500-1000 μg/L for C2. This range is intended to balance maintaining therapeutic efficacy with minimizing the risk of adverse events. Then we propose a dose of 4.5-5.5 mg/kg/d for patients under 40 years old and 3.5-4.5 mg/kg/d for those over 40 years old to achieve target concentrations.

In summary, we provide a comprehensive analysis of AEs associated with cyclosporine maintenance in AA patients undergoing IST. We also propose optimal cyclosporine concentration ranges and suggest age-adjusted dosing strategies to ensure both efficacy and safety.

(1) AA Patients presented with cyclosporine associated AEs were with higher C0 (trough) and C2 (peak) levels. (2) We recommend the optimal concentration ranges as 150-250 μg/L for C0 and 500-1000 μg/L for C2 for AA patients receive cyclosporine treatment. (3) We propose a dose of 4.5-5.5 mg/kg/d for patients under 40 years old and 3.5-4.5 mg/kg/d for those over 40 years old to achieve target concentrations.