Mycophenolate Mofetil Dose and Early Acute Cellular Rejection Post Cardiac Transplantation

Abstract

Early acute cellular rejection (ACR) after orthotopic heart transplantation (OHT) is associated with adverse long-term outcomes. Data on whether the Mycophenolate mofetil (MMF) dose has any impact on rates of early ACR is lacking. The target MMF dose studied in clinical trials for immunosuppression with OHT has ranged from 2 to 3gm/day. In January of 2016 due to an increase in infectious complications, we modified our institutional policy whereby the target MMF dose was lowered from 3 gm/day to 2gm/day. In this analysis, we examined rates of early rejection stratified by target MMF dose. We performed a retrospective analysis of consecutive OHT recipients at a single center from January 2015 to July 2019. Patients were divided into two groups based on the target MMF dose (3gm vs. 2 gm/day). The rates of ACR warranting a change in immunosuppressive regimen within 4 weeks of OHT (1R/1B or ≥ 2R) were compared between the two groups. Data on other factors that could impact early ACR such as age, gender, race, induction immunosuppression, and PRA was also collected. Univariate and multivariate-adjusted statistical analyses were performed. Of 169 OHT, mean age 53 years and 26% females, 67 patients were in the MMF 3gm/day group (Group 1) and 102 were in the 2 gm/day group (Group 2). Baseline characteristics were similar in both groups. The average daily dose of MMF for the first week after OHT was 2245 ± 724 mg in Group 1 and 1866 ± 525 mg in Group 2 (p<0.001). The incidence of early ACR was higher in Group 2 compared to Group 1 (22% vs. 12%, p=0.06) (Figure1). In this single-center study of OHT recipients comparing daily target MMF dose of 3gm with 2gm in the early post OHT period, there was a trend towards early ACR in the 2gm/day MMF dose group. This suggests that a higher MMF dose of 3gm/day, if tolerated, may help lower rates of early ACR. Further investigation in a larger sample is warranted to validate this finding.