Acute graft-versus-host disease is a leading cause of mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Calcineurin inhibitors (CNIs) such as tacrolimus are a leading strategy in the attempt to prevent GVHD, but it’s unclear what serum levels are optimal. A poster presented at the annual conference of the Hematology/Oncology Pharmacy Association described a study that aimed to define the optimal tacrolimus serum concentration to prevent acute GVHD.
“Management of CNI therapy is challenging given its narrow therapeutic index and significant interpatient variability due to drug interactions, genomics, hepatic function, and protein binding,” wrote the University of Chicago Medicine researchers, led by Jennifer Collins, PharmD, BCOP, clinical pharmacy specialist. Trough tacrolimus levels less than 5 ug/ml have been associated with increased risk of GVHD. High levels (more than 12 ug/ml) reduce GVHD risk but increase risk of toxicities. But that range is broad, and study findings have varied.
The researchers conducted a single-center retrospective chart review of 340 adult patients who received matched allogeneic HSCT. They calculated tacrolimus levels every 10 days from day 0 to day 100, and they recorded incidence and grade of acute GVHD.
The study did not find a difference in tacrolimus trough levels among patients who developed acute GVHD versus those who did not develop the complication. They assessed differences by conditioning regimen, T-cell depletion, and donor type (matched related versus matched unrelated) but found no significant differences. In addition, the study did not find that higher tacrolimus levels were associated with acute kidney injury or neurotoxicity.
The research team commented: While we did not observe a difference in tacrolimus trough concentrations in relation to acute GVHD incidence, we confirmed that generalized targets are appropriate and safe, regardless of T-cell depletion and donor type.”