Cytomegalovirus infection and ganciclovir resistance caused by UL97 mutations in pediatric transplant recipients

Abstract

Cytomegalovirus (CMV) infection may cause serious disease after hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT), but few reports describe ganciclovir (GCV) resistance in pediatric patients. This study was performed to describe the clinical impact of CMV infection with UL97 mutation in pediatric transplant recipients. Quantitative surveillance data for CMV infection in pediatric patients between October 2001 and February 2007 at the University of Washington were analyzed. Testing for UL97 mutation was performed in selected patients with prolonged CMV viremia despite therapy. Data associated with the detection of UL97 mutations were reviewed. CMV was detected in 89 pediatric transplant recipients. Among these, 39 had undergone HCT and 50 SOT (12 heart, 22 kidney, 15 liver, and 1 bilateral lung transplants). CMV with at least one UL97 sequence variation was detected in 5 patients: 4 HCT recipients (4/39, 10%) and 1 heart transplant recipient (1/50, 2%). All 5 pediatric patients were CMV seropositive before transplantation. Underlying conditions included chronic myelogenous leukemia, primary immunodeficiency disorders, and hypoplastic left heart syndrome. One known GCV drug-resistant mutation was detected in 2 HCT recipients (A594V). Three strain variants with mutations considered to have no significant impact on UL97 function (H469Y, N510S, and D605E) were detected. Two of these 5 patients died, 1 because of uncontrolled CMV infection and 1 with other complications. UL97 drug-resistant mutations occur in pediatric transplant recipients with CMV viremia and can cause serious disease. Screening for mutations conferring resistance to CMV antivirals should be considered for patients with persistent viremia during therapy and the sequences of UL97 mutations evaluated.