Ganciclovir and Acyclovir Reduce the Risk of Post‐Transplant Lymphoproliferative Disorder in Renal Transplant Recipients

Funch, Donnie; Walker, Alexander M.; Schneider, G; Ziyadeh, Najat J.; Pescovitz, Mark D.

doi:10.1111/j.1600-6143.2005.01115.x

Cited by 249 publications

(155 citation statements)

References 26 publications

(30 reference statements)

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“…A subsequent multi-center case-control study evaluating renal-only transplants found up to an 83% reduction in the risk of PTLD, with variation between anti-viral agents. Notably, ganciclovir was associated with a 38% risk reduction of early PTLD for each 30 days during an individual's first year post-transplant [30]. In a study of lung transplant patients, researchers also found a reduction of PTLD from 4.2% among a historical comparison group to 0.76% in recipients of prophylaxis with either acyclovir, valacyclovir, or ganciclovir [25].…”

Section: Discussionmentioning

confidence: 79%

Valganciclovir for the Suppression of Epstein-Barr Virus Replication

Yager

Magaret

Kuntz³

et al. 2017

The Journal of Infectious Diseases

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Valganciclovir for the Suppression of Epstein-Barr Virus Replication Jessica Eve YagerChair of the Supervisory Committee:Professor Anna Wald Department of EpidemiologyEpstein-Barr virus (EBV), a common herpesvirus, is the main causative agent of infectious mononucleosis.Following primary infection, EBV persists in host cells and can cause B cell transformation, leading to the development of EBV-associated malignancies. The role for antiviral therapy in treating and preventing EBV-associated disease remains unclear. Using oral swabs collected from a randomized, double-blind, placebo-controlled crossover study that our group had previously conducted, we sought to determine the impact of valganciclovir on both the rate and quantity of oral EBV shedding. Twenty-six men were randomly assigned to receive either oral valganciclovir, 900mg daily, or oral placebo once daily for eight weeks. Participants then received no study drug for a two week "washout period," followed by the alternate treatment (valganciclovir or placebo) for a second eight-week period. Valganciclovir reduced the proportion of days on which EBV was detected by 72% (relative risk 0.28, 95% confidence interval 0.08-0.55; p=0.003), and reduced the quantity of virus detected by 0.77 logs (95% confidence interval 0.62-0.91 logs; p<0.001). These results were consistent regardless of participants' HIV status and use of antiretroviral therapy. These findings could have significant clinical applications in both the treatment and prevention of EBV-associated disease. 4Background and Significance:

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Section: Discussionmentioning

confidence: 79%

Valganciclovir for the Suppression of Epstein-Barr Virus Replication

Yager

Magaret

Kuntz³

et al. 2017

The Journal of Infectious Diseases

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“…A multicenter case-control study matched 100 biopsy-confirmed, PTLD-positive renal transplant recipients to 375 healthy renal transplant recipient controls. In the first year post-transplant, the study found a 38% lower PTLD risk (odds ratio, 0.62; 95% confidence interval, 0.38 -1.0) for every 30 days of ganciclovir treatment [49].…”

Section: Preventionmentioning

confidence: 96%

Malignancy After Solid Organ Transplantation: An Overview

2008

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Disclosure:This article discusses the use of acitretin (manufactured by Connetics) for prophylaxis of non-melanoma skin cancers; cyclophosphamide * (Bristol-Myers Squibb), adriamycin * (Pharmacia), prednisone * (Pfizer), vindesine (Lilly/EG Labo; not available in the U.S.), rituximab * (Genentech), and monoclonal anti-IL-6-antibody (multiple manufacturers) for post-transplant lymphoproliferative disorder (PTLD) (clinical trial); vincristine * (Lilly/Gensia Sicor) and bleomycin * (Bristol-Myers Squibb) for PTLD and Kaposi's sarcoma (KS); liposomal daunorubicin (Gilead) for KS (indicated for HIV-associated KS); paclitaxel (BristolMyers Squibb) for KS (indicated for AIDS-associated KS); imatinib (Novartis) and bevacizumab (Genentech) for KS; and matrix metalloproteinase inhibitor COL-3 (CollaGenex) for KS (clinical trial). ( * Drugs marked with asterisks are indicated for use in malignant lymphomas generally, but no specific mention is made of PTLD.)The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers. LEARNING OBJECTIVESAfter completing this course, the reader should be able to:1. Describe the most common malignancies encountered after solid organ transplantation.2. Discuss the pathogenesis of malignancy after solid organ transplantation. Administer standard treatment for common post-solid organ transplantation malignancies.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT CASE PRESENTATIONA 49-year-old man with no prior medical history initially presented with severe dyspnea progressive over 6 months.The patient underwent an open-lung biopsy that confirmed the diagnosis of idiopathic pulmonary fibrosis. He was assessed for lung transplantation. An extensive pretransplant

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“…25,26 Moreover, prophylactic antiviral therapies are effective in preventing posttransplant lymphomas, particularly in children, highlighting the role of primary EBV infection or EBV reactivation in their development. 19,20,27 During primary EBV infection and EBV reactivation, active viral replication occurs. 28 Viral replication is the hallmark of the lytic phase and EBV replication has an important role in lymphomagenesis.…”

Section: Discussionmentioning

confidence: 99%

“…4,9,[18][19][20] However, the decision to treat and the type of therapy a patient receives largely rely only on clinical features such as: current dosing, type of allograft, history of rejection, or infections. Thus, the effect of antiviral therapies is very controversial probably due to not considering the amount of intratumoral viral load and the EBV replication stage in the decision to treat a patient.…”

mentioning

confidence: 99%

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

et al. 2014

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Post-transplant lymphoproliferative disorders are life-threatening complications following hematopoietic or solid organ transplantation. They represent a spectrum of mostly EBV-driven lymphoplasmacytic proliferations. While the oncogenic effect of EBV is related to latent infection, lytic infection also has a role in lymphomagenesis. In vitro, EBV replication is linked to plasma cell differentiation and XBP1 activation, although this phenomenon has never been addressed in vivo. We analyzed for the first time latent and lytic intratumoral EBV infection in a series of 35 adult patients with a diagnosis of post-transplant lymphoproliferative disorder (26M/9F, median age 54 years). A complete EBV study was performed including the analysis of the latent EBER, latent membrane protein-11, and EBV nuclear antigens as well as the immediate-early BZLF1/ ZEBRA and early BMRF1/EADE31 lytic genes. XBP1 activation was assessed by nuclear protein expression. EBV infection was observed in 28 (80%) cases being latency II and III the most frequently observed 22 (79%). Intratumoral EBV replication was detected in 17 (60%) cases. Among these, XBP1 activation was observed in 11/12 evaluable cases associated with strong cytoplasmic immunoglobulin expression consistent with plasma cell differentiation. Intriguingly, the combination of latency III infection and EBV replication identified a high-risk subgroup of patients with significantly shorter survival (overall survival at 1 year 18% vs 48%) and early-onset (median of 7 vs 26 months) post-transplant lymphoproliferative disorder. Moreover, these patients appear to be more heavily immunosuppressed, so they exhibit lower rates of rejection and graft vs host disease but higher rates of cytomegalovirus reactivation. In conclusion, EBV replication is associated with plasma cell

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Ganciclovir and Acyclovir Reduce the Risk of Post‐Transplant Lymphoproliferative Disorder in Renal Transplant Recipients

Abstract: Given its association with Epstein-Barr virus (EBV), there is considerable interest in assessing the

Cited by 249 publications

References 26 publications

Valganciclovir for the Suppression of Epstein-Barr Virus Replication

Valganciclovir for the Suppression of Epstein-Barr Virus Replication

Malignancy After Solid Organ Transplantation: An Overview

In vivo intratumoral Epstein–Barr virus replication is associated with XBP1 activation and early-onset post-transplant lymphoproliferative disorders with prognostic implications

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