Adenovirus infection after pediatric bone marrow transplantation

Hale, G; Heslop, Helen E.; Krance, Robert A.; Brenner, Malcolm K.; Jayawardene, Deepthi; Dk, Srivastava; Patrick, Christian C.

doi:10.1038/sj.bmt.1701563

Cited by 240 publications

(233 citation statements)

References 24 publications

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“…3,5 The probable cause is an increase in the number of high-risk patients undergoing HSCT. Subsequently, newfound awareness of AdV may have led to more intense surveillance strategies reinforced by the application of new sensitive methods for molecular diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…The most feared sequelae in immunocompromised individuals include enteritis, hemorrhagic cystitis, nephritis, fulminant hepatitis and disseminated disease; the mortality rate can be as great as 80%. [1][2][3][4][5][6][7][8] The risk of disseminated disease has been shown to correlate positively with viral load as measured by quantitative PCR methods. [9][10][11] Cidofovir has emerged as the primary therapy for AdV infection.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Öhrmalm

Lindblom

Omar

et al. 2010

Bone Marrow Transplant

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Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In parallel with a routine CMV surveillance program, plasma from 20 children and 77 adults was analyzed by quantitative PCR for detection of AdV DNA. In addition, in 12 unselected patients, the presence of AdV-specific T cells were analyzed by enzyme-linked immunosorbent spot (ELISPOT) at 1 to 3 months after transplantation. A total of 5 of 97 (5%) patients had detectable AdV DNA in peripheral blood. Only one patient had high titers and none developed AdV disease. BM as a source of stem cells and myelodysplastic syndrome as the indication for transplantation were independently associated with higher risk of acquiring AdV infection. AdV-specific T cells were detected in 7 (58%) of 12 patients. Although AdV DNA was found in peripheral blood by quantitative PCR in 5% of patients undergoing allogeneic HSCT, the present surveillance program did not have a significant effect on the clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Öhrmalm

Lindblom

Omar

et al. 2010

Bone Marrow Transplant

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“…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.…”

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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

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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.

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“…Serotype analysis was done on five patients and serotype 11 was found to be the most common isolate. Unrelated donor and total body irradiation (TBI) were the two independent risk factors found in this study [4]. In most series, HC is commonly caused by adenovirus subgroup B and serotype 11 [5].…”

Section: Discussionmentioning

confidence: 76%

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

Sahu

Prakash

Khadwal

et al. 2015

Indian J Hematol Blood Transfus

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Post bone marrow transplant patients are susceptible to atypical infections, especially viral pathogens. The risk increases many folds in cases of allogeneic transplantation, which also receive GVHD prophylaxis. Viral pathogens like cytomegalovirus and herpes are the common ones encountered during follow-up period. However, in recent times there have been reports of a variety of disease manifestations of rare viruses like polyoma virus and adenovirus. These viral infections may play a crucial role in morbidity and mortality in immunocompromised patients. We hereby elaborate the follow-up course of a 36-year-old post allogeneic transplant patient of acute myeloid leukemia who developed adenovirus related haemorrhagic cystitis. Treatment with oral ribavirin lead to dramatic improvement in symptomatology within a week. This cases re-emphasizes the fact that after ruling out the commoner pathogens, it's of utmost importance to strongly consider the atypical pathogens in such cases. Case-ReportA 36-year-old gentleman, known case of acute myeloid leukemia (FAB-M2) was admitted on Day ?380 of allogeneic stem cell transplant with 7 days history of lower urinary tract symptoms (LUTS), dysuria, increased urine frequency, urgency of urine, and haematuria. In the background, patient received inj. busulphan (0.8 mg/kg every 6 h for 4 days) and inj. cyclophosphamide (60 mg/kg/day for 2 days) as conditioning regimen. Peri-transplant period was unremarkable for any complication. No features of high dose cyclophosphamide induced cystitis or acute graft versus host disease (aGVHD) was noted. He received cyclosporine-A (5 mg/m 2 ) and methotrexate 15 mg/m 2 on Day ?1 and 10 mg/m 2 on Day ?3, ?6 and ?11 as prophylaxis for GVHD (Fig. 1). Tapering of immunosuppression was started on Day ?80 onwards and patient did not have any evidence of GVHD till Day ?256. Following which he developed lichenoid changes in the oral mucosa, dryness of eyes and hypopigmented patches over the face and upper trunk involving \25 % of body surface (Fig. 2). Liver function tests showed total bilirubin levels-1.2 g/dL, SGOT, SGPT and SALP of 92, 139, 392 IU/mL, respectively. After clinical examination, laboratory evaluation and liver?skin biopsy he was diagnosed as moderate cGVHD (Table 1). As a result additional immunosuppressive medications in the form of mycophenolate (1000 mg BD) along with oral prednisolone was started. He also received topical cyclosporine eye drops (0.05 %) for conjunctival GVHD. Following immunosuppressive therapy symptoms related to GVHD started improving (Fig.

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Adenovirus infection after pediatric bone marrow transplantation

Cited by 240 publications

References 24 publications

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

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

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

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