Retrospective Analysis of Tacrolimus Levels: The First 56 Days Following Allogeneic Hematopoietic Stem Cell Transplant and Patient Outcomes.

Background: Despite prophylaxis, acute graft-versus-host disease (aGVHD) occurs in up to 40% to 60% of patients undergoing an allogeneic hematopoietic stem cell transplantation (alloHSCT). Tacrolimus remains a common GVHD prophylactic medication used in combination with mycophenolate or methotrexate.

Objective: The purpose of this study was to compare tacrolimus levels up to day +56 to clinical outcomes in patients who underwent alloHSCT.

Methods: This was a retrospective cohort study of adult patients who underwent alloHSCT between January 2009 and April 2019 at Oregon Health and Science University (OHSU) Hospital. A logistic regression analysis was performed using SAS software to evaluate the association between tacrolimus concentration range and the GVHD grade outcome.

Results: There were 295 patients included in the study. The median patient age was 53 years (range 18-72), the majority were males (55%), with a median comorbidity index of 2 (range 0-9). Most patients received peripheral blood stem cell transplant (95%). The median tacrolimus levels were divided into 4 groups: (1) between 3.8 and 4.9 ng/mL, (2) 5.0 and 7.9 ng/mL, (3) 8.0 and 9.9 ng/mL, and (4) 10.0 and 10.7 ng/mL in 8 (2.7%), 206 (69.8%), 71 (24.1%), and 10 (3.4%) of patients, respectively. The odds ratio of 0.193 (95% confidence interval [CI]: 0.045-0.836) suggested that patients in the tacrolimus 8 to 12 ng/mL range were approximately 80.5% less likely to have grade 3 to 4 aGVHD compared to those in the 5 to 8 ng/mL range.

Conclusion and relevance: Overall, we found that higher levels of tacrolimus (range 8-12 ng/mL) in the first 8 weeks post-transplant were associated with improved outcomes without increased rate of relapse.