Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State‐of‐the‐art and real‐life current approach

Abstract

The important insights gained over the past years in diagnosis and treatment of invasive adenoviral infections provide new paradigms for the monitoring and clinical management of these life-threatening complications. A meeting was held to discuss and subsequently disseminate the current advances in our understanding of the aetiology/pathogenesis and future treatment options facilitating effective control or prevention of adenovirus-related diseases in the allogeneic haematopoietic stem cell transplant setting. Invited experts in the field discussed recent progress with leading members of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation at the "State-of-the-art" Meeting in Poznan, Poland, in October 2017. In this review article, the panel of experts presents a concise summary of the current evidence based on published data from the last 15 years and on recent achievements resulting from real-life practice. The present position statement reflects an expert opinion on current approaches to clinical management of adenovirus infections in patients undergoing allogeneic haematopoietic stem cell transplant and provides graded recommendations of the panel for diagnostic approaches and preemptive therapy reflecting the present state of knowledge.

Association between adenovirus viral load and mortality in pediatric allo-HCT recipients: the multinational AdVance study

“…For cytolytic viral infections such as AdV, plasma viremia may provide a quantitative measure of tissue damage in the most commonly affected organs: the gastrointestinal tract, lungs, liver, or kidneys [17]. In our study, over half the pediatric allo-HCT recipients who developed AdV viremia surpassed the level of ≥1000 copies/ml, an accepted threshold for the initiation of preemptive treatment [7,18]. Analyses of AdV viral load in these patients revealed a strong association with risk of mortality.…”

“…Pediatric allogeneic hematopoietic stem cell transplant (allo-HCT) recipients with nonmatched sibling sources are at high risk of developing adenovirus (AdV) infections, particularly during the immediate posttransplant period before immune reconstitution has occurred [1][2][3][4][5][6][7]. AdV viremia is widely considered to be an indicator of disease dissemination [6,8,9], with higher levels of AdV viremia (≥1000 copies/ml) shown to be associated with mortality in single-center studies [7,10]. Guidelines have thus recommended antiviral treatment in high-risk patients with AdV viremia [11].…”

“…While there are few treatment options for AdV infection in allo-HCT recipients, the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation recommends, whenever feasible, tapering immunosuppression and considering off-label treatment with intravenous (IV) cidofovir when AdV viremia is documented [7]. However, data supporting efficacy of IV cidofovir are limited, and treatment responses are generally observed only when immune reconstitution has occurred [11,12].…”

Community-Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs

“…In allogeneic HCT, HAdV replication is more frequently detected, which is, however, mostly due to the widespread screening of blood and gastrointestinal specimens from a-or presymptomatic patients considered to be at highest risk, such as children and those receiving alemtuzumab therapies (203). Conversely, HAdV is less frequently reported in respiratory specimens from allogeneic HCT patients with RTID (204,205).…”

“…Conversely, HAdV is less frequently reported in respiratory specimens from allogeneic HCT patients with RTID (204,205). Accordingly, the levels and dynamics of HAdV in different anatomic sites is not well understood, with the exception of blood and stool samples, and no generalized thresholds using international calibrators have been established (203,206,207). A large retrospective study of 687 allogeneic HCT patients identified HAdV in 64 (9.3%) cases presenting mostly as gastrointestinal disease or hemorrhagic cystitis but in 3 (0.5%) cases as HAdV pneumonitis, which eventually had a lethal outcome (204).…”