Impact of Mycophenolate Dosing on CMV Rates in Heart Transplant Recipients

Purpose The relationship between rejection and infection in heart transplant (HT) recipients is a delicate balance. Cytomegalovirus (CMV) remains a serious complication in this patient population with a reported incidence of 20-30%. The manufacturer-recommending dose of mycophenolate (MMF) in HT patients is 3000mg/day; although many patients require dose reductions due to side effects or intolerance. The aim of this study was to evaluate the impact of MMF dosing on the incidence of CMV within the first year post transplant. Methods This study retrospectively reviewed adult patients who underwent cardiac transplantation between September 2005 and September 2017. CMV viremia, defined as a positive serum quantitative PCR, was recorded up to one year post transplant. MMF dose was documented at time of index discharge and classified based on cumulative daily dose (3000mg/day, 2000mg/day, or <2000mg/day). CMV prophylactic agent, duration of therapy and time to first positive CMV were also recorded. Institution guidelines for post-transplant care included 3 months CMV prophylaxis based on donor/recipient CMV match (CMV+/- received valganciclovir, CMV+/+ or CMV -/+ received valacyclovir and CMV -/- received acyclovir). Biopsy proven acute rejection (2R) was collected to explore correlations to CMV viremia and graft outcomes. Results 157 patients were included in the study - 68 pts (43.3%) received MMF 3000mg/day, 65 pts (41.4%) received 2000mg/day and 24 pts (15.3%) received <2000mg/day. Baseline characteristics, including CMV risk, were similar between groups. The overall incidence of CMV at one year was 31% (CI 24.06-39.08). Patients receiving 3000mg/day of MMF had the highest rate of CMV compared to 2000mg/day and <2000mg/day (38% vs 27.69% vs 20%, p=0.14). The average time to first positive CMV was 165 days. Patients receiving valganciclovir had the highest incidence of CMV viremia at one year compared to those receiving valacyclovir and acyclovir (44.78% vs 25% vs 8.33%, p=0.004). This relationship was true at all mycophenolate doses. Rejection was not shown to be correlative to either MMF dose or CMV viremia. Conclusion This study illustrates a trend towards higher incidence of CMV with larger daily mycophenolate doses. Rejection was not found to be correlative to mycophenolate dosing, indicating doses of 2000mg/day may be a safe option for patients at moderate/high risk for CMV. The relationship between rejection and infection in heart transplant (HT) recipients is a delicate balance. Cytomegalovirus (CMV) remains a serious complication in this patient population with a reported incidence of 20-30%. The manufacturer-recommending dose of mycophenolate (MMF) in HT patients is 3000mg/day; although many patients require dose reductions due to side effects or intolerance. The aim of this study was to evaluate the impact of MMF dosing on the incidence of CMV within the first year post transplant. This study retrospectively reviewed adult patients who underwent cardiac transplantation between September 2005 and September 2017. CMV viremia, defined as a positive serum quantitative PCR, was recorded up to one year post transplant. MMF dose was documented at time of index discharge and classified based on cumulative daily dose (3000mg/day, 2000mg/day, or <2000mg/day). CMV prophylactic agent, duration of therapy and time to first positive CMV were also recorded. Institution guidelines for post-transplant care included 3 months CMV prophylaxis based on donor/recipient CMV match (CMV+/- received valganciclovir, CMV+/+ or CMV -/+ received valacyclovir and CMV -/- received acyclovir). Biopsy proven acute rejection (2R) was collected to explore correlations to CMV viremia and graft outcomes. 157 patients were included in the study - 68 pts (43.3%) received MMF 3000mg/day, 65 pts (41.4%) received 2000mg/day and 24 pts (15.3%) received <2000mg/day. Baseline characteristics, including CMV risk, were similar between groups. The overall incidence of CMV at one year was 31% (CI 24.06-39.08). Patients receiving 3000mg/day of MMF had the highest rate of CMV compared to 2000mg/day and <2000mg/day (38% vs 27.69% vs 20%, p=0.14). The average time to first positive CMV was 165 days. Patients receiving valganciclovir had the highest incidence of CMV viremia at one year compared to those receiving valacyclovir and acyclovir (44.78% vs 25% vs 8.33%, p=0.004). This relationship was true at all mycophenolate doses. Rejection was not shown to be correlative to either MMF dose or CMV viremia. This study illustrates a trend towards higher incidence of CMV with larger daily mycophenolate doses. Rejection was not found to be correlative to mycophenolate dosing, indicating doses of 2000mg/day may be a safe option for patients at moderate/high risk for CMV.