Evaluation of Cytomegalovirus-Specific T Cell Response Can Improve Risk Stratification of CMV Infection in Heart Transplant Recipients

Abstract

Purpose Current assessment of risk of cytomegalovirus (CMV) infection in CMV+ heart transplant (HT) recipients is poor. This has led to universal prophylaxis, but this strategy has significant costs and side-effects. We aimed to evaluate the impact of determining CMV-specific T cell responses against 2 CMV antigens (IE-1 and pp65), using the IFN-γ ELISPOT on use of prophylaxis and the incidence of CMV infection in CMV+ HT recipients. Methods We prospectively evaluated all CMV+ HT recipients in 1 institution in whom we performed an IFN-γ ELISPOT prior to HT and 2 weeks post-HT. The ELISPOT result could be low risk (IE-1>23 spots and pp65>133 spots) or not low risk. This information plus clinical assessment led to deciding between pre-emptive therapy or prophylaxis with Valgancyclovir 900 mg daily for 3 months. We collected incidence of CMV viremia (any positive CMV PCR), CMV infection (CMV PCR>1500 IU/ml) and CMV disease and incidence of leucopenia ( Results We included 29 HT recipients with 26 IFN-γ ELISPOTs pre-HT and 28 IFN-γ ELISPOTs post-HT. Mean age was 56 years old, 24% female and 45% were emergency HT. Donor CMV serology was positive in 62% of cases. Induction therapy was given in 90% of patients. All received Tacrolimus + Mycophenolate mophetil + steroids. Figure 1 shows the main outcomes of the study. One patient died before the second IFN-γ ELISPOT determination and is not included. No patient with a low risk ELISPOT post-HT developed CMV infection, giving a positive predictive value of the test of 100%. The incidence of leucopenia was 7(39%) from 18 patients treated with prophylaxis. 2 needed G-CSF. Conclusion Evaluation of CMV-specific T cell response using the ELISPOT assay in CMV+ HT recipients can help stratify risk for CMV infection. Patients with a low risk ELISPOT 2 weeks post-HT may safely undergo pre-emptive therapy.