Adenovirus Is a Key Pathogen in Hemorrhagic Cystitis Associated with Bone Marrow Transplantation

Abstract

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

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].…”

Rare viral infections in children receiving hemopoietic stem cell transplant

“…27 However, it must be remembered that CMV and adenovirus 28 also have been associated with the development of hemorrhagic cystitis, sometimes in association with BK virus. [28][29][30][31][32] Among the papovavirus family, JC virus has been reported as a cause of multifocal leukoencephalopathy in cancer patients receiving chemotherapy and rituximab, in one case combined with autologous HSCT. 33,34 Parvovirus B19 has been reported to cause persistent infection (several months or years) in immunocompromised hosts mainly due to impairment of B-cell function.…”

Recipient seropositivity for adenovirus type 11 (AdV11) is a highly predictive factor for the development of AdV11-induced hemorrhagic cystitis after allogeneic hematopoietic SCT

“…As adenovirus serotype 11 (AdV11) with striking tropism for the urinary system is a pathogen predominantly responsible for late-onset HC after allogeneic HSCT in Japan, 1,2 it is important to assess the risk of AdV-HC and to make a rapid diagnosis of HC for early intervention.…”

“…According to the published criteria, 3 we recorded grade 2 or higher HC as a clinically important complication in HSCT patients and performed viral cultures of their urine. As Akiyama et al 2 reported that the viral culture is equivalent to PCR for diagnosis of AdV-HC, we classified HC into AdV-HC and nonAdV-HC based on the culture results. Among 69 subjects, 15 patients developed late-onset HC during the 1-year follow-up period ( Figure 1a).…”

“…1,2,9,10 The influence of seropositivity for AdV was controversial. 1,2,9,10 In this study, we used a neutralizing antibody test to detect anti-AdV11 antibodies because this test is serotype-specific and can detect IgG antibodies for longer period after primary infection than can the complement fixation test. This prospective study revealed that the cumulative incidence of AdV-HC was 64% in the seropositive patients, but only 2% in the seronegative patients (log-rank test, Po0.001).…”