Association Between Tacrolimus Levels and Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Graft-versus-host-disease (GVHD) is a life threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). The calcineurin inhibitor tacrolimus is commonly used in combination with other immunosuppressants to prevent GVHD; however the optimal serum target concentration for tacrolimus in this population remains unknown. A retrospective review was conducted to determine whether an association exists between tacrolimus concentrations and transplant-related outcomes, specifically acute GVHD, as well as the rate of renal toxicity and mortality. Data from 203 patients who underwent an allogeneic HSCT from a related (n1⁄495) or unrelated (n1⁄4108) donor between January 1, 2003 and December 31, 2011 at a large academic hospital was analyzed. Sixty-two (31%) patients developed acute GVHD within the first 30 days following allogeneic stem cell transplant. Median tacrolimus concentrations at day 0, 7, 14, and 28 were 11.2, 13.8, 13.5 and 10.2 ng/mL, respectively among those who developed acute GVHD. Patients who did not develop acute GVHD had similar tacrolimus concentrations of 10.4,13.1,12.3 and 9.9 ng/mL for the same respective time points. Serum tacrolimus concentrationswere similar across all grades of GVHD and therewas no correlation between drug concentrations with respect to renal toxicity. Patients who developed renal dysfunction (n1⁄418) had tacrolimus concentrations similar to the median concentration of the entire cohort, including those who did not experience renal toxicity. Overall mortality among the 203 included patients was 49%. Mortality was higher among patients who developed acute GVHD (55%) than in patients who did not experience the disease (47%). The results of this analysis support previous conclusions that tacrolimus blood concentrations are not associated with acute GVHD within the first 30 days post allogeneic HSCT.