Ganciclovir

Crumpacker, Clyde S.

doi:10.1056/nejm199609053351007

Cited by 403 publications

(270 citation statements)

References 77 publications

Supporting

Mentioning

258

Contrasting

Unclassified

Order By: Relevance

“…In addition, these drugs do not eradicate latently infected B cells. 41,42 The reports that prophylactic antiviral drugs minimize PTLD risk have been somewhat unconvincing, involving very small number of patients in observational studies. Each investigator defined 'high-risk' differently: some included only patients with elevated EBV viral loads, while others included EBVnegative patients receiving organs from EBV-positive donors, or patients receiving high-dose immunosuppression or specific antilymphocyte therapy.…”

Section: Antiviral Therapymentioning

confidence: 99%

Post-transplant lymphoproliferative disorder: a review

Loren

Porter

Stadtmauer

et al. 2003

Bone Marrow Transplant

246

201

View full text Add to dashboard Cite

Summary:Post-transplant lymphoproliferative disorder (PTLD) represents a spectrum of Epstein-Barr virus-related (EBV) clinical diseases, from a benign mononucleosis-like illness to a fulminant non-Hodgkin's lymphoma. In the setting of hematopoietic stem cell transplantation, PTLD is an often-fatal complication occurring relatively early after transplant. Risk factors for the development of PTLD are well established, and include HLA-mismatching, T-cell depletion, and the use of antilymphocyte antibodies as conditioning or treatment of graft-versushost disease. Early recognition of PTLD is particularly important in the SCT setting, because PTLD in these patients tends to be rapidly progressive. Familiarity with the clinical features of PTLD and a heightened level of suspicion are critical for making the diagnosis. Surveillance techniques with EBV antibody titers and/or polymerase chain raction (PCR) may have a role in some highrisk settings. Immune-based therapies such as monoclonal anti-B-cell antibodies, interferon-a, and EBV-specific donor T cells, either as treatment for PTLD or as prophylaxis in high-risk patients, represent promising new directions in the treatment of this disease.

show abstract

Section: Antiviral Therapymentioning

confidence: 99%

Post-transplant lymphoproliferative disorder: a review

Loren

Porter

Stadtmauer

et al. 2003

Bone Marrow Transplant

246

201

View full text Add to dashboard Cite

show abstract

“…3 Current strategies for the prevention of CMV disease aim at preventing end-organ disease by using ganciclovir or valganciclovir prophylaxis 4,5 or ganciclovir pre-emptive therapy, initiated upon early detection of CMV infection by antigenemia or CMV DNA in plasma. 5,6 The relative merits of both strategies have been debated extensively in the literature. 7,8 The major drawback limiting the use of oral ganciclovir is its poor bioavailability, which precludes therapeutic use by oral administration.…”

Section: Introductionmentioning

confidence: 99%

“…7,8 The major drawback limiting the use of oral ganciclovir is its poor bioavailability, which precludes therapeutic use by oral administration. 6 This has now changed with the introduction of valganciclovir, which is an orally administered prodrug of ganciclovir with good bioavailability. Previous pharmacokinetic studies showed similar drug exposure to ganciclovir after a single oral dose of 900 mg valganciclovir as compared to an intravenous dose of 5 mg/kg ganciclovir.…”

Section: Introductionmentioning

confidence: 99%

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients

Heiden

Kalpoe

Barge

et al. 2006

Bone Marrow Transplant

View full text Add to dashboard Cite

The efficacy and safety of oral valganciclovir was compared to ganciclovir i.v. in pre-emptive treatment of cytomegalovirus (CMV) in T-cell-depleted allogeneic stem cell transplant (allo-SCT) recipients. A therapeutic guideline was developed to allow the safe application of valganciclovir in allo-SCT recipients requiring CMV therapy. In total, 107 consecutive transplant recipients were evaluated. Cytomegalovirus DNA load in plasma was monitored longitudinally; details on antiviral therapy and treatment responses were analyzed retrospectively. Fifty-seven CMV treatment episodes were recorded in 34 patients: 20 with valganciclovir (900 mg twice-daily) and 37 with ganciclovir (5 mg/kg twice-daily). Median CMV DNA load reduction was 0.079 and 0.069 log 10 copies/ml/ day in the ganciclovir and valganciclovir group, respectively. Good response on CMV DNA load (reduction below 3.0 log 10 copies/ml) was observed in 75.7% of ganciclovir and 80.0% of valganciclovir treatment episodes. Severe adverse effects were not observed and CMV-related disease did not occur. However, the percentage of patients receiving erythrocyte transfusion was higher in the group of patients receiving ganciclovir as compared to valganciclovir (41 versus 20%, P ¼ 0.116). In conclusion, pre-emptive treatment with valganciclovir and ganciclovir, led to similar reduction of CMV DNA load. Oral valganciclovir is an attractive and safe alternative for pre-emptive CMV treatment in T-cell-depleted allo-SCT recipients.

show abstract

“…Shortly after initial infection, EBV enters into a latent state, whereupon only select "latent" genes are expressed, thereby evading the host immune surveillance mechanism, and establishing a lifelong persistent infection in the host [14]. Nucleoside analogs such as acyclovir (ACV) or ganciclovir (GCV) are often used as antiviral drugs against acute EBV and other herpesvirus infections [15,16]. The virally-encoded thymidine kinase enzyme converts these analogs to their monophosphate forms, which after conversion into the triphosphate form by host kinases, are then incorporated in newly-synthesized DNA, leading to premature termination of DNA synthesis and killing of the infected cell by apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Short, discontinuous exposure to butyrate effectively sensitizes latently EBV-infected lymphoma cells to nucleoside analogue antiviral agents

Ghosh¹,

Forman²,

Akinsheye³

et al. 2007

Blood Cells, Molecules, and Diseases

View full text Add to dashboard Cite

Antiviral drugs alone have been unsuccessful in the treatment of Epstein Barr virus (EBV)-associated malignancies because the virus maintains a latent state of replication in these tumors. In recent years, novel therapeutic approaches are being investigated wherein lytic replication of the virus is induced prior to the use of cytotoxic antiviral drugs. The choice of suitable agents to induce lytic replication has been a critical step in this novel approach. We have previously demonstrated that butyrate derivatives induce a lytic pattern of EBV gene expression in patient-derived EBV-positive lymphoblastoid cell lines and, together with nucleoside analog ganciclovir, effectively reduce or eliminate tumor growth in humans. Butyrate has drawbacks as a therapeutic agent, however, as constant intravenous infusion is required to achieve detectable plasma levels of this drug. In this study, we investigated whether discontinuous exposure to butyrate is capable of initiating lytic-phase gene expression and thymidine kinase induction, and sensitizing EBV-positive lymphoma cells to ganciclovir-mediated cell growth arrest and apoptosis. We demonstrate that multiple daily 6 hr exposures of the EBV-positive Burkitt's lymphoma cell line P3HR1 to butyrate induced sustained expression of the EBV lytic-phase protein BMRF. Viral thymidine kinase was also induced by intermittent exposure, although to a lower level than with continuous exposure treatment. However, discontinuous exposure to butyrate in combination with ganciclovir induced a similar level of tumor cell growth inhibition as did continuous treatment, as measured by serial enumeration of viable cells, MTT cell proliferation assays, and measurement of cellular DNA content. We further demonstrated that those cells which survived initial exposure to butyrate plus ganciclovir remained susceptible to further cycles of combination treatment. These findings suggests that continuous infusion of butyrate may not be necessary for maintaining viral thymidine kinase gene expression and sensitization to anti-viral agents in EBV-associated tumors, and that therapeutic regimens which employ more convenient, discontinuous exposure to butyrate may also be effective clinically.

show abstract

Ganciclovir

Cited by 403 publications

References 77 publications

Post-transplant lymphoproliferative disorder: a review

Post-transplant lymphoproliferative disorder: a review

Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients

Short, discontinuous exposure to butyrate effectively sensitizes latently EBV-infected lymphoma cells to nucleoside analogue antiviral agents

Contact Info

Product

Resources

About