Epidemiology and long-term outcomes of cytomegalovirus DNAemia and disease in pediatric solid organ transplant recipients

Abstract

Despite prevention strategies, cytomegalovirus (CMV) remains a common infection in pediatric solid organ transplant recipients (SOTR). We sought to determine the frequency, associations with, and long‐term outcomes of CMV DNAemia in pediatric SOTR. We performed a single‐center retrospective cohort study, including 687 first time SOTR ≤21 years receiving universal prophylaxis from 2011 to 2018. Overall, 159 (23%) developed CMV DNAemia, the majority occurring after completing primary prophylaxis. CMV disease occurred in 33 (5%) SOTR, 25 (4%) with CMV syndrome and 10 (1%) with proven/probable tissue‐invasive disease. CMV contributed to the death of three (0.4%) patients (all lung). High‐risk (OR 6.86 [95% CI, 3.6–12.9]) and intermediate‐risk (4.36 [2.3–8.2]) CMV status and lung transplantation (4.63 [2.33–9.2]) were associated with DNAemia on multivariable analysis. DNAemia was associated with rejection in liver transplant recipients (p < .01). DNAemia was not associated with an increase in graft failure, all‐cause mortality, or other organ‐specific poor outcomes. We report one of the lowest rates of CMV disease after SOTR, showing that universal prophylaxis is effective and should be continued. However, we observed CMV morbidity and mortality in a subset of patients, highlighting the need for research on optimal prevention strategies. This study was IRB approved.

CMV infection and management among pediatric solid organ transplant recipients

“…This was the case for analyses involving all patients, as well as the subset of only at‐risk SOT recipients. This finding is consistent with a recent study by Valencia Deray and colleagues, who found that DNAemia was not associated with graft failure, all‐cause mortality, or other organ‐specific poor outcomes among 687 pediatric SOT recipients 9 . Although these authors found that rejection was more common among pediatric liver transplant recipients who experienced DNAemia, this association was not evaluated using multivariable analyses.…”

“…Valencia Deray and colleagues, who found that DNAemia was not associated with graft failure, all-cause mortality, or other organ-specific poor outcomes among 687 pediatric SOT recipients. 9 Although these authors found that rejection was more common among pediatric liver transplant recipients who experienced DNAemia, this association was not evaluated using multivariable analyses. Meanwhile, we found that CMV disease was associated with a strong hazard of negative outcomes among all patients, as well as the at-risk subgroup, which indicates a potential association in a larger study.…”

“…In a recent single‐center study of 97 pediatric heart transplant recipients, 8 high‐risk CMV status and CMV infection were associated with acute rejection on univariate analyses, but these effects were not significant on multivariable analyses. Finally, in a recent study of nearly 700 pediatric SOT recipients, rejection was more common among liver transplant recipients with CMV DNAemia but not among recipients of other organs 9 …”

“…Finally, in a recent study of nearly 700 pediatric SOT recipients, rejection was more common among liver transplant recipients with CMV DNAemia but not among recipients of other organs. 9 Prior to the routine use of antivirals, end-organ or symptomatic CMV disease developed in as many as 40% of pediatric SOT recipients within the first year post-transplant. 10 As administration of antiviral prophylaxis has become routine, more recent data suggest that disease occurs in fewer than 10%-20% of pediatric SOT recipients.…”

Incidence of cytomegalovirus DNAemia in pediatric kidney, liver, and heart transplant recipients: Efficacy and risk factors associated with failure of weight‐based dosed valganciclovir prophylaxis

“…Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in solid organ transplant recipients (SOTR) 1 Rates of CMV infection and/or disease in pediatric SOTR vary from 8%–38% in heart recipients, 2–4 14%–22% in kidney recipients, 4–6 and 10%–40% in liver recipients 1,4,7,8 …”