The impact of routine mycophenolate mofetil drug monitoring on the treatment of cardiac allograft rejection

Introduction, Mycophenolate mofetil (MMF) is a unique immunosupressive agen t that has been shown to be efficacious in the treatment of cardiac allogra ft rejection. The utility of therapeutic drug monitoring on rejection proph ylaxis and treatment is inconclusive. This study was undertaken to evaluate the incidence of rejection in relation to MMF trough level following heart transplantation. Methods. Between May 1998 and February 1999, we retrospectively analyzed th e clinical outcome of 215 heart transplant patients who had routine monitor ing of MMF trough level at the time of scheduled endomyocardial biopsy. Pat ients were divided into three groups according to the time interval post tr ansplant, and were evaluated in relation to the MMF trough level. Group I, 104 patients within 6 months of transplant; Group II, 90 patients, 6-12 mon ths post transplant; and Group III, 71 patients beyond one year of transpla nt. Fifty patients had samples in more than one group. Rejection was define d as Grade greater than or equal to 3A based on ISHLT criteria. Mean follow -up period was 179+/-52 days. Results, A significantly decreased incidence of rejection was noted in the samples with MMF trough level greater than or equal to 2 mg/l compared to t hose with less than 2 mg/l in patients evaluated within the first year of t ransplant (Group I: 8.8% vs. 14.9%, Group II: 4.2% vs. 11.3%, both P=0.05). In the presence of therapeutic cyclosporine (CSA) or tacrolimus (FK) blood levels, the incidence of rejection decreased significantly when MMF trough level was greater than or equal to 2 mg/l compared to samples with MMF tro ugh level <2 mg/l (3.6% vs. 14.4%, P=0.005). No significant difference was noted in the presence of subtherapeutic CSA or FK levels (15.4% vs. 13.9%, P=NS) Conclusions. Monitoring of MMF trough levels may play a role in the managem ent of cardiac transplant recipients during the first year post transplant.