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Adenovirus viremia and infection after reduced-intensity allogeneic hematopoietic stem cell transplant: should we institute a routine screening program?

Adenovirus (ADV) has been identified as an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT) [1–8]. Polymerase chain reaction (PCR)–based assays now allow rapid quantification of ADV load in the blood. However, unlike cytomegalovirus (CMV), for which preemptive therapy is well established, the monitoring and treatment of ADV viremia or infection remain controversial, particularly given the limited treatment options. To establish recommendations for monitoring of ADV following HSCT, several questions would need to be answered: (1) What is the incidence of ADV viremia in HSCT recipients? (2) Is there a correlation between viral load and organ involvement as well as survival? (3) Are there risk factors (either patient or transplant characteristics) that can predict viremia and outcomes? (4) Can these risk factors be mitigated? (5) Are there effective treatments and has early treatment been shown to affect outcome? The reported incidence of ADV viremia and associated morbidity and mortality vary widely in the literature. For example, consistently high rates of ADV infection have been reported in pediatric populations, with an incidence of up to 84% in children <5 years of age in one series [5, 6]. In contrast, in a large retrospective review that included almost 2900 transplant recipients, the incidence was 3%, with an associated 26% mortality [3]. Adenovirus infection in this study was detected via culture or immunohistochemistry, possibly underestimating the true incidence, as more sensitive PCR was not used. Similarly, many of the older reports either did not include PCR monitoring or were case-finding studies. More recent studies have included PCR monitoring. One study prospectively tested for ADV in a cohort of 76 allogeneic HSCT patients by testing stool, urine, and pharyngeal specimens every other week for 6 months after transplant, and performing blood PCR only in patients with a positive tissue sample. The reported incidence was 19.7% with a 3% mortality rate [4]. Several other small studies have reported an incidence of about 5% when routine screening with blood PCR was performed [9, 10]. A recent large retrospective review reported a similar 5% incidence in 539 patients tested for ADV by PCR [8]. Mortality was high in this group, and 7 of the 27 patients succumbed to ADV disease. Both T-cell depletion and high viral loads were identified as risk factors for fatal ADV. T-cell depletion has been identified as a risk factor for ADV infection in a number of studies [4, 9, 11–13]. In particular, the use of in vivo T-cell depletion with alemtuzumab has been associated with an increased risk of ADV infection [4, 12, 13]. Additional risk factors for ADV viremia are young age, acute graft-versus-host disease, and the use of cord blood as a stem cell source [4, 11, 12, 14, 15]. As reported in this issue of Clinical Infectious Diseases, Sive and colleagues instituted weekly blood quantitative PCR monitoring for ADV in 116 patients receiving reduced-intensity conditioning with alemtuzumab. In addition to weekly blood PCR until day 100, symptomatic patients had evaluation of stool Received 23 July 2012; accepted 6 August 2012; electronically published 16 August 2012. Correspondence: Miguel-Angel Perales, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 298, New York, NY 10065 (peralesm@mskcc.org). Clinical Infectious Diseases 2012;55(10):1371–2 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cis695