Adenovirus Infections in Adult Recipients of Blood and Marrow Transplants

Abstract

Adenoviruses are increasingly recognized pathogens that affect blood and marrow transplant (BMT) recipients. Experiences with 2889 adult BMT recipients were reviewed to study the incidence, clinical spectrum, risk factors for dissemination, response to therapy, and outcome of adenovirus infections. Eight-five patients (3%) were diagnosed by means of culture (n=85) or culture and histopathological examination (n=6). Nine patients had asymptomatic viruria, and 76 had symptomatic infections, which included upper respiratory tract infection (n=20), enteritis (n=18), hemorrhagic cystitis (n=10), pneumonia (n=15), and disseminated disease (n=13). The overall mortality rate was 26%. A higher mortality rate was observed among patients with pneumonia (73%) and disseminated disease (61%). Risk factors for dissemination included receipt of an allogeneic transplant, presence of graft-versus-host disease (GVHD), and receipt of concurrent immunosuppressive therapy. Intravenous ribavirin was not associated with an appreciable benefit among 12 patients who received this treatment. In conclusion, adenovirus infections are an important cause of morbidity and mortality in adult BMT recipients, particularly allogeneic transplant recipients with GVHD who are receiving immunosuppressive therapy. The need for an effective, nontoxic antiviral therapy is apparent.

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

“…In the series of 2889 adult BMT recipients studied by Alberto et al, 9 patients had asymptomatic viruria and 76 patients had symptomatic infections. HC was the third most common infection caused by adenovirus after upper respiratory tract infections and enteritis in this study [3]. Hale et al reported HC as the most common manifestation followed by gastroenteritis and pneumonia in his study on 206 pediatric post-BMT patients.…”

“…Amongst these, ribavirin (nucleoside analogue) is found to be the next most efficient drug [15]. English literature review shows variable results of treatment with ribavirin in various studies [3,[16][17][18]. The majority of the published literature reports intravenous use of ribavirin as therapy for adenoviral infections.…”

Comparison of HSV-1 thymidine kinase-dependent and -independent inhibition of replication-competent adenoviral vectors by a panel of drugs

“…42 In some cases therapy was successful, [43][44][45][46][47][48] but many patients died despite RBV treatment. [49][50][51][52][53][54][55][56] Furthermore, cidofovir (CDV), an acyclic nucleoside phosphonate that has activity against virtually all DNA viruses including adenovirus, 57,58 has been evaluated for disseminated adenovirus disease with limited success. [59][60][61] Reports of successful alternative strategies are less common and include an apparent beneficial effect of donor leukocyte infusion, 53,54 intravenous immunoglobulin, 62 and ganciclovir(GCV) treatment.…”

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).…”

“…Therapeutic options for ADV disseminated disease are still very limited (1,7,10,36,38,39,41,43,(45)(46)(47). Intravenous or aerosolized ribavirin (1,7,19,38,45,47), vidarabine (7), and cidofovir (7,36,(45)(46)(47) are included in antiviral agents, and the intravenous administration of immunoglobulin (12), the discontinuation of antibiotics (36), donor lymphocyte infusion (7) (38).…”