Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients

Abstract

BackgroundCytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue.MethodsWe performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed.ResultsFor the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p = 0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p = 0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival.For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p = 0.005) and among those with asymptomatic CMV infection (36%, p = 0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p = 0.042) and asymptomatic CMV infection (55%, p = 0.018) than patients without CMV infection (84%).ConclusionsA lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

Incidence, Risk Factors and Outcomes of Delayed-onset Cytomegalovirus Disease in a Large Retrospective Cohort of Lung Transplant Recipients

“…This may reflect the widespread use of anti-CMV prophylaxis for at least 3 months after lung transplant 11-14, 20, 21 , thereby leading to a delay in the onset of CMV disease. Almost a quarter of new-onset CMV disease in this study population was coded as CMV pneumonitis.…”

“…CMV infection has been demonstrated to be associated with an increased risk of acute allograft rejection 1, 6 and bronchiolitis obliterans syndrome (BOS) 7-11 . Because of its association with poor outcomes, preventive anti-CMV strategies in lung transplant recipients are utilized 12 , with the majority of transplant centers using anti-CMV prophylaxis with oral valganciclovir or intravenous ganciclovir for 3 to 6 months.…”

The Cell Biology of Cytomegalovirus: Implications for Transplantation

“…Both direct and indirect effects are often present simultaneously, and the relative clinical contributions of any of these mechanisms are uncertain. In general, CMV seropositivity and receipt of seropositive organs and viremia are linked in many, but not all, studies to diminished long-term graft function (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Furthermore, most studies have indicated that successful antiviral prophylaxis has a beneficial effect on long-term graft function (8).…”

Pediatric lung transplantation

“…With the advent of gene-based diagnostic modalities, and the corresponding enhancement in diagnostic sensitivity, treatment has become more focused. Whether such strategies diminish the incidence of bronchioloitis obliterans is not known (40). Despite effective antiviral therapy, CMV infection remains a source of both morbidity and mortality.…”