Calcineurin inhibitor monitoring in allogeneic hematopoietic cell transplantation: time to move beyond solid organ transplant paradigms

Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been the backbone of graft-versus-host disease prophylaxis in allogeneic hematopoietic cell transplantation for more than four decades. Yet, the pharmacological framework governing their therapeutic drug monitoring has been significantly imported from solid organ transplantation. This critical narrative review argues that this extrapolation is scientifically unsound. The unique biological environment of allogeneic hematopoietic cell transplantation characterized by toxic conditioning regimens, profound hematologic changes, systemic inflammation, and an unparalleled drug interaction landscape creates pharmacokinetic and pharmacodynamic conditions for which solid organ transplant-derived targets are inadequate. We critically appraise the quality of evidence underpinning current therapeutic drug monitoring practices, examine the historical divide between cyclosporine and tacrolimus use, and propose a research agenda directed at developing hematopoietic transplant-specific precision immunosuppression strategies.