Optimizing the use of cyclosporin in allogeneic stem cell transplantation

Cyclosporin remains the most widely used immunosuppressive agent in patients undergoing allogeneic stem cell transplantation (SCT). The increased awareness of the impact of the intensity of post-transplant immunosuppression on determining outcome after allogeneic SCT has resulted in a re-examination of whether cyclosporin is currently being optimally used in this population of patients. Recent studies in solid organ transplantation have questioned whether the use of trough levels provides the most accurate reflection of the immunosuppressive actions of cyclosporin and alternative strategies to monitor cyclosporin dosage after liver and kidney transplantation are increasingly being used. As a result there is now interest in examining whether there is scope for translating these advances into the arena of haematopoietic transplantation. In this paper, we will review the rationale underlying the current schedules for dosing and monitoring cyclosporin after allogeneic SCT and identify specific areas in which the use of cyclosporin requires re-evaluation. These include evaluation of whether patient outcome would be improved by using peak cyclosporin levels to determine dosing schedules, analysis of optimal cyclosporin dosing schedules in patients undergoing reduced intensity allografts and investigation of surrogate markers of cyclosporin's immunosuppressive activity.