Adenovirus-Associated Hemorrhagic Cystitis Treated with Intravenous Ribavirin

Murphy, Gregory F.; Wood, David P.; McRoberts, J. William; Henslee‐Downey, P. Jean

doi:10.1016/s0022-5347(17)36149-9

Cited by 83 publications

(33 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 The high calculated IC 90 of B250 mM might explain the fact that reported clearance of adenovirus infection occurred most frequently in patients with adenovirus-associated hemorrhagic cystitis due to high bladder concentrations of RBV. 43,44,53,74,75 Intravenous RBV administration is associated with anemia due to intravascular hemolysis and bone marrow-suppressive effects. 76 The antiadenoviral effects of CDV, which is approved for the treatment of CMV retinitis in AIDS patients, have been described previously for several serotypes including Ad5.…”

Section: Discussionmentioning

confidence: 99%

“…29,32,40,41 So far, experience is greatest with parenteral administration of the broad-spectrum antiviral ribonucleoside ribavirin (RBV), 41 which has documented activity against adenovirus in vitro. 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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2003

View full text Add to dashboard Cite

Replication-competent adenoviral vectors hold the promise to be more efficient gene delivery vehicles than their replicationdeficient counterparts, but they are also associated with a higher risk for adverse effects, especially in light of the fact that there is no established effective therapy for serious, disseminated adenovirus infection. To assess whether the therapeutic options to inhibit adenoviral replication can be enhanced by expressing a suicide gene, we examined the antiadenoviral effects of 15 drugs against wild-type adenovirus type 5 (Ad5) and an Ad5-based replication-competent vector expressing herpes simplex virus-1 thymidine kinase (HSV-tk) (Ad.OW34) using a real-time polymerase chain reaction -based assay and flow cytometry. Ad5 and Ad.OW34 were highly susceptible to the fluorinated pyrimidine analogs 5-fluoro-2 0 -deoxyuridine (FUdR), 5-fluorouridine (FUR), and trifluorothymidine (TFT), with a mean 50% inhibitory concentration (IC 50 ) ranging from 0.12 to 0.32 mM. The mean IC 50 of ribavirin and cidofovir (CDV) for Ad5, the most frequently used drugs to treat adenovirus disease, was 6.87 and 3.19 mM, respectively. In contrast to Ad5, the Ad.OW34 vector was susceptible to (E)-5-(2-bromovinyl)-2 0 -deoxyuridine (BVdU, IC 50 0.09 mM), ganciclovir (GCV, IC 50 0.19 mM), and acyclovir (ACV, IC 50 32.04 mM). Additionally, we demonstrated in an animal model that Ad.OW34 vector replication can be inhibited significantly by GCV, CDV, and TFT by 35.2, 7.7, and 3.7-fold, respectively, compared to untreated animals. The observed antiadenoviral effects were primarily not through cell killing, since the in vitro 50% cytotoxic concentrations (CC 50 ) were more than 1000 times higher than the antiadenoviral IC 50 of the drugs examined, even in cells stably expressing HSV-tk. Since for HSV-tk-dependent inhibition of adenoviral vectors, stability of HSV-tk expression is crucial, we examined Ad.OW34 vector stability, by passaging the vector 10 times serially in the presence of 10 mM GCV. The HSV-tk/GCV system neither changed the susceptibility of Ad.OW34 to GCV significantly nor detectable vector rearrangements occurred, suggesting that the system might be suitable as a fail-safe mechanism to stop adenoviral vector replication.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Additional risk factors for severe HC identified from this study are use of busulfan, presence of GVHD, and age at transplantation (10-30 years of age compared to age under 10), consistent with some earlier reports. 14,[31][32][33] It is unclear, however, whether GVHD per se can manifest as HC, 34 or whether GVHD-related immunosuppressive therapies increase the chances of opportunistic infections 35 and subsequently cause HC. Notably, patients with ALD had an unusually high risk of severe HC (five out of 12 transplants), suggesting this group of patients may have an abnormal sensitivity to the chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for severe hemorrhagic cystitis following BMT

Seber

Shu

DeFor

et al. 1998

Bone Marrow Transplant

155

137

View full text Add to dashboard Cite

Summary:Hemorrhagic cystitis (HC) is a common toxicity of preparative regimens for bone marrow transplantation (BMT). Severe HC often requires prolonged and expensive hospitalization, and occasionally can result in death. To investigate the risk factors for severe HC, we conducted a retrospective study among 1908 patients who received BMTs at the University of Minnesota during 1974 to 1993. A previous report from our institution reported on 977 of these patients. We identified all patients with genitourinary complication within 100 days post-BMT from the BMT database. Medical charts for these patients were reviewed to determine whether the patient had HC and also the grade of HC. A total of 208 HC cases were identified during the study period. Of them, 92 patients had severe HC, an incidence of 5% (95% CI = 4-6%). We found that grade II-IV graftversus-host disease (RR = 2.56; 95% CI = 1.43-4.56), use of busulfan (RR = 2.69; 95% CI = 1.35-5.35), and age at transplant (RR = 2.20; 95% CI = 1.27-3.81, for age of 10-30 compared to age of 0-9) were related to an increased risk of HC. In contrast, transplant year was inversely associated with the risk of HC (trend test, P Ͻ 0.01). We did not find any significant difference in HC with the use of prophylactic Mesna. Keywords: bone marrow transplantation; complications; hemorrhagic cystitis; risk factors; adenovirus; cytomegalovirus Outcome after bone marrow transplantation (BMT) has improved over the past 20 years, 1 but preparative regimenrelated toxicities (RRT) remain a major limitation to further progress. Hemorrhagic cystitis (HC) is a common RRT. 2 In the BMT setting, HC occurring in the early post-transplant period is more frequently associated with the use of cyclophosphamide (CY), while late occurring HC frequently results from viral infections (eg BK virus, adenovirus type II). 3-8 CY has been widely used for conditioning patients undergoing BMT. The drug is hydroxylated in the liver, generating 4 hydroxy-CY, phosphoramide mustard, and acrolein. Excreted in the urine, acrolein can cause edema,

show abstract

“…2 Intravenous ribavirin has been reported to be useful in AD-HC. [4][5][6] Oral ribavirin has been used for hepatitis C, but its role in adenovirus infections is unclear.…”

mentioning

confidence: 99%

“…However, the efficacies of ribavirin remain controversial. [4][5][6]10 Thus, more studies are needed to determine if this antiviral works for AD-HC. …”

mentioning

confidence: 99%