Invasive adenoviral infections in T‐cell‐depleted allogeneic hematopoietic stem cell transplantation: high mortality in the era of cidofovir

Abstract

Mortality rates of ADV pneumonitis after allogeneic HSCT remain high in the era of cidofovir. Clinical trials are needed to evaluate management strategies for this life-threatening 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

“…29,[31][32][33] However, the observations made at our and other institutions indicate that initiation of antiviral treatment at the time of first detection of viremia may not prevent progression to severe AdV disease in many instances, and that earlier initiation of preemptive treatment could therefore be beneficial. 1,7,11,21,30,[33][34][35][36] Adenoviruses are known to persist in epithelial cells and lymphoid tissue, and AdV infections occurring during the posttransplant period appear to result from virus reactivation in most instances. Our observations revealed that virtually all patients who experienced systemic AdV infection had the virus detectable in serial stool specimens, with or without clinical symptoms of enteritis, before the onset of viremia.…”

“…1 Although molecular detection of viremia was shown to precede the onset of clinical symptoms of disseminated viral disease, preemptive antiviral treatment with virustatic agents such as cidofovir, ribavirin or foscarnet administered at first detection of the virus in PB failed to prevent lethal outcome of AdV disease in most instances. 1,11,17,18 It has been shown that the adoptive transfer of donor-derived AdV-specific T-lymphocytes may provide an attractive treatment option in patients with invasive AdV infection, but the favorable outcome observed upon in vivo expansion of the transferred T cells appeared to be related to the early onset of adoptive T-cell transfer during the course of infection. 19,20 These observations suggested that timely initiation of antiviral treatment, possibly before the occurrence of invasive infection, might be beneficial.…”

“…[13][14][15] However, AdV infections in immunocompromised patients tend to become invasive, and disseminated disease is associated with very high mortality. 3,11,16 We have established a pan-adenovirus real-time PCR assay and demonstrated that AdV detection in peripheral blood (PB) of patients during the post-transplant period is associated with very high morbidity and mortality. 1 Although molecular detection of viremia was shown to precede the onset of clinical symptoms of disseminated viral disease, preemptive antiviral treatment with virustatic agents such as cidofovir, ribavirin or foscarnet administered at first detection of the virus in PB failed to prevent lethal outcome of AdV disease in most instances.…”

“…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. [8][9][10][11][12] Infections can cause localized disease such as enteritis, upper respiratory tract infection, encephalitis or cystitis. [13][14][15] However, AdV infections in immunocompromised patients tend to become invasive, and disseminated disease is associated with very high mortality.…”

Generation of cytotoxic T-cell lines using overlapping pentadecapeptides derived from conserved regions of the adenovirus hexon protein

“…Disseminated adenovirus (Ad) infection is among the most lethal post-HPCT complications, especially in paediatric patients (Flomenberg et al, 1994). The importance of T-cell immunity in preventing Ad infection is evidenced by higher disease incidence associated with targeted T cell-specific treatment for graft versus host disease (GVHD) (La Rosa et al, 2001) and in recipients of T cell-depleted grafts, where T-cell recovery may be delayed (Chakrabarti et al, 2002;Symeonidis et al, 2007). Antiviral agents, including cidofovir and ribavirin, may be effective in reducing viral loads in patients with at least partial T-cell immunity, but have been less effective in the absence of viral immunity, indicating the need for alternative therapies (Feuchtinger et al, 2007;Lenaerts et al, 2008;Neofytos et al, 2007).…”