Safety and Effectiveness of Low-Dose Cytomegalovirus Valganciclovir Prophylaxis in CMV Seropositive Lung Transplant Recipients

Abstract

<h3>Purpose</h3> We executed a universal prophylactic strategy in lung transplant (LTx) recipients to prevent CMV infections. All patients received valganciclovir (VGCV) prophylaxis with biweekly blood sample monitoring to detect CMV. Patients were treated with conventional triple-drug immunosuppression including mycophenolic acid, without induction. Retrospective analysis was performed to assess the effectiveness and safety of this protocol. <h3>Methods</h3> We included 166 adult LTx patients (total 174 LTxs) operated between 2004-2016, with the median follow up of 7.32 years. Our CPG for D+/R- recipients and for recipients with cystic fibrosis included 900mg VGCV daily for 12 months, and for R+ patients a low-dose 450mg VGCV daily for 6 months, starting within first week after LTx. The prophylactic dosage was adjusted based on renal function. R+ groups were grouped together due to the low-dose protocol. <h3>Results</h3> Five patients died before the completion of the prophylaxis. During prophylaxis, the overall incidence of CMV infection was 7.1% (12/169), and that of CMV disease was 2.3% (4/169). D+/R- recipients had 10-fold risk of CMV infection compared to R+ recipients (5/148 vs. 7/21, p<0.0005). In 10.0% (17/169) of the recipients, the prophylaxis was prematurely ceased due to leukopenia. There was no statistically significant difference in the prevalence of leukopenia between R+ and D+/R- groups (54.9% vs. 76.2%, p=0.06). In 65,4% of R+ recipients, VGCV prophylaxis was prolonged after 6 months with mean duration of 297±72 days, and in 29.6 % of R+ recipients (42/142) the daily dosage was increased to 900mg. However, the prolongation of VGCV prophylaxis in R+ recipients failed to affect the activation of CMV infection or disease after discontinuation of the prophylaxis (6.1% vs 10.1%, p=0.52). Only one patient (D+/R-) developed ganciclovir resistance. At 5 years, the incidence of CLAD was 57.1% in D+/R- recipients compared to 37.3% in R+ recipients (p=0.07). However, there was no difference in the overall patient survival between groups (73.9% vs. 71.4%, p=0.87). <h3>Conclusion</h3> The low-dose VGCV CMV prophylaxis is safe and efficient in CMV seropositive recipients.