Adenoviral infection after allogeneic stem cell transplantation (SCT): report on 130 patients from a single SCT unit involved in a prospective multi center surveillance study

Abstract

Summary:The incidence of adenovirus (AV) infections following SCT was determined in a prospective multicenter trial. Over 1 year, 130 consecutive patients undergoing allogeneic SCT at Essen University Hospital were included and followed for 6 months. Source of stem cells was blood in 68 cases. Fifty-eight patients had HLA-identical sibling donors. Throat swabs, urine and stool samples were screened weekly for AV antigen and DNA by ELISA and nested PCR, respectively. In 35 cases adenovirus infection was detected. There was no seasonal variation. Throat swabs were positive in 24, urine in 12, and stool in 11 cases, resulting in a cumulative risk of infection of 29%. The incidences of AV infection of the respiratory, gastrointestinal and urinary tract were 19%, 10%, and 9%, respectively, and infections were diagnosed after a median (range) interval of 44 (−2-179), 37 (−2-168), and 53 (17-153) days after transplantation. On multivariate analysis, presence of AV antibody in the donor and acute graft-versus-host disease grade IV were found to be independent risk factors for AV infection. Eleven patients had AV isolated from more than one site and five patients had probable AV disease. We were not able to identify patients in whom AV infection was the leading cause of death. The majority of patients infected with AV suffered from severe acute graft-versus-host disease often accompanied by other opportunistic infections, such as aspergillosis or CMV reactivation. Nineteen out of 36 patients who died during the observation period had AV infection. In summary, AV infection after allogeneic SCT was observed in a substantial number of patients. In addition to well-known risk factors for viral infection after SCT we were able to demonstrate that a positive AV antibody test in the donor is an important risk factor for AV infection. Further studies are needed, how- Hemopoietic stem cell transplantation has been used with increasing success for treatment of patients with various hematological neoplasms, but the procedure itself is associated with significant morbidity and mortality. Infectious complications are major factors contributing to transplantrelated mortality. In the past, the most common viral infections following marrow transplantation were caused by herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV). With the introduction of acyclovir for HSV and VZV and ganciclovir treatment for CMV, fatalities caused by these viruses have decreased dramatically. Over the same period of time, reports on fatal viral infections caused by adenovirus (AV) have been published by several groups. [1][2][3] The most common clinical manifestation of AV infection is hemorrhagic cystitis, 4 followed by gastroenteritis, pneumonitis, and liver failure. 5 In addition, AV can cause pancreatitis, nephritis, and disseminated disease leading to mortality rates ranging from 18 to 60%. The outcome of AV disease depends on patient age, type of immunosuppression, and AV serotype. 6 An increasing incidence of AV infection...

Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation

“…[1][2][3][4][5][6][7] To date, more than 50 human AdV serotypes showing different tissue tropism have been identified, and the number of new putative serotypes is increasing. They have been divided into six major subgroups (subgenera or species A-F) on the basis of the oncogenic, hemagglutinating, morphological and DNA sequence properties.…”

A Rare Case of Hemorrhagic Cystitis in Allogeneic Hematopoietic Stem Cell Transplant Patient

“…However, like our case, there are reports when patients have acquired adenovirus infection after 100 days post-BMT [7]. Regarding the associated risk factors involved in acquiring adenovirus infections are type of transplant (allogeneic vs autologous), history of aGVHD, use of immunosuppressive drugs, use of conditioning regimen containing cyclophosphamide, fludarabine or TBI, younger age group, asymptomatic viremia, unrelated donor, adenovirus antibody status of donor, T cell depletion of stem cell harvest [6,[8][9][10][11].…”

“…In most series, HC is commonly caused by adenovirus subgroup B and serotype 11 [5]. Commonly, adenovirus infection has been documented in the first 100 days of post-BMT period [5,6]. However, like our case, there are reports when patients have acquired adenovirus infection after 100 days post-BMT [7].…”

Adenovirus Fulminant Hepatic Failure: Disseminated Adenovirus Disease after Unrelated Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia

“…Bordigoni et al (7) revised the Wisconsin criteria, which defines definite ADV disease as the presence of typical ADV nuclear inclusion in routine histopathology and/or a positive culture from affected tissue, originally described by Flomenberg et al (12) (2, 8, 11-13, 21, 39), the intensity of immunosuppressive therapy (38), the isolation of ADV from two or more sites (12,39), HLA-mismatched or unrelated transplants (1,21), T-cell depletion transplants (11) with/ without ATG, CD34+ positive selection transplant, lymphocytopenia (11), ADV antibody status of the donors (2), allogeneic transplantation (38,39), and a conditioning regimen with TBI (8). No (17,19), 5 (14-16, 18), and 32 (40) (41), serum (42,43), or urine (42,44) (41).…”