Assessment of Mycophenolic Acid Levels on Biopsy Proven Rejection and Adverse Effects in Pediatric Heart Transplant Recipients

Purpose Therapeutic ranges of Mycophenolic Acid (MPA) concentrations have not been established in pediatric heart transplant recipients. There are limited data supporting are under the concentration-time curve (AUC) in adult heart transplant on outcomes such as rejection, but AUC monitoring may be not be feasible in clinical practice. The purpose of our study is to evaluate the relationship between mycophenolic acid (MPA) trough levels and incidence of biopsy proven rejection and adverse effects in pediatric heart transplant patients. Methods A single-center retrospective chart review was performed on patients receiving heart transplant between Jan 2011 and Dec 2015. Patients included for analysis were ≤18 years at transplant and received maintenance immunosuppression with tacrolimus, mycophenolate, and a corticosteroid. Endomyocardial biopsy grades up to one-year post transplant and simultaneous MPA levels were recorded. Patients with acute cellular rejection scores of 2R or 3R or immunopathologic evidence of antibody mediated rejection were considered as biopsy proven acute rejection (BPAR). Leukopenia, gastrointestinal side effects, and mycophenolate dose decreases were also recorded. Results A total of 47 patients were included in the final analysis. There were no significant differences in baseline demographics between patients who had BPAR and those who did not. Overall 24% of patients had at least 1 incidence of BPAR after heart transplant. The mean MPA trough levels between the group of patients with rejection (2.4 ug/mL +/- 1.62) and those without rejection (2.46 ug/mL +/- 1.74) was not significantly different (p=0.38). Mean MPA trough levels also were also not consistent when examining rejection by time from transplant. Only examining by individual MPA trough levels on biopsy days did we observe a significantly lower MPA trough 1.6 ug/mL +/- 1.05 in those with rejection versus those without 2.5 ug/mL +/- 1.69 (p=0.02). The mean MPA level associated with a dose decrease due to an adverse effect between these two groups was not significant. Conclusion MPA trough levels may have a relationship with incidence of biopsy proven rejection or with incidence of adverse events within one-year post transplant in this population. Controlled prospective studies with are warranted to further evaluate this potential relationship.