A Trial of Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Lung Transplant Recipients

Humar, Atul; Kumar, Deepali; Preiksaitis, Jutta K.; Boivin, Guy; Siegal, Deborah; Fenton, Jayne; Jackson, K.; Nia, Sarah; Lien, Dale

doi:10.1111/j.1600-6143.2005.00866.x

Cited by 90 publications

(74 citation statements)

References 24 publications

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“…Second, although all patients in our study received intravenous ganciclovir prophylaxis, CMV prophylaxis has continued to evolve and now often includes longer prophylactic periods. Although there is no standard of care regarding CMV prophylaxis among lung transplantation centers, reports of longer CMV prophylactic periods (up to 6 mo) have resulted in rates of CMV-P similar to those in this report (11,19). These data would indicate that longer course ganciclovir prophylaxis delays, but does not ultimately prevent, CMV disease.…”

Section: Discussionsupporting

confidence: 64%

“…This ''late-onset CMV disease,'' often defined as disease after the prophylactic period ends, has been associated with increased risk for graft failure after kidney transplantation and increased mortality in liver transplant recipients despite adequate treatment for CMV disease once detected (8,9). Several retrospective reports have also suggested that late-onset disease occurs frequently in lung recipients despite courses of prophylaxis as long as 3-6 months (10,11).…”

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confidence: 99%

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Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

Snyder¹,

Finlen-Copeland²,

Turbyfill³

et al. 2010

Am J Respir Crit Care Med

142

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Rationale: Cytomegalovirus pneumonitis is one of the most prevalent opportunistic infections after lung transplantation. Early studies reported that cytomegalovirus pneumonitis was a risk factor for chronic allograft dysfunction. More recently, in the era of routine prophylaxis and ganciclovir treatment, the adverse impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome has been challenged. Objectives: We hypothesized that cytomegalovirus pneumonitis contributes to adverse outcomes in the current antiviral era. We sought to define the impact of treated cytomegalovirus pneumonitis on bronchiolitis obliterans syndrome and survival in a large singlecenter cohort (n 5 231) of consecutive patients undergoing lung transplantation from 2000 to 2004, all receiving short-course ganciclovir prophylaxis. Methods: Transbronchial biopsies were performed at defined intervals with prospective cytomegalovirus immunostaining on every biopsy (n 5 1,887). Cox proportional hazards models were used to assess the relationship between treated cytomegalovirus pneumonitis and clinical outcomes. Measurements and Main Results: Forty-nine (21%) recipients developed cytomegalovirus pneumonitis a median of 106 days after transplantation. Treated cytomegalovirus pneumonitis within the first 6 months after transplantation significantly increased the risk for bronchiolitis obliterans syndrome (P 5 0.001; hazard ratio, 2.19; 95% confidence interval, 1.36-3.51) and post-transplantation death (P 5 0.02; hazard ratio, 1.89; 95% confidence interval, 1.11-3.23). This risk persisted when cytomegalovirus pneumonitis was considered as a time-dependent predictor as well as in multivariable models controlling for other risk factors. Conclusions: Cytomegalovirus pneumonitis affects more than 20% of lung transplant recipients. Despite treatment, it increases the risk for bronchiolitis obliterans syndrome and death. More effective preventive strategies for cytomegalovirus pneumonitis are needed to improve long-term outcomes after lung transplantation.

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Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

Snyder¹,

Finlen-Copeland²,

Turbyfill³

et al. 2010

Am J Respir Crit Care Med

142

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“…Some other sequence variants, such as V466M (3) and T659I (35), were reported as a change from a pretreatment sequence after therapy. T659I was classified as a GCV resistance marker without specific phenotypic data (16,20,33). The findings in Table 1 add to several other UL97 sequence variants that did not confer GCV resistance after BAC mutagenesis (27).…”

Section: Discussionmentioning

confidence: 85%

Recombinant Phenotyping of Cytomegalovirus UL97 Kinase Sequence Variants for Ganciclovir Resistance

Chou

2010

Antimicrob Agents Chemother

116

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A strain of human cytomegalovirus, T2211, modified from standard laboratory strain AD169 to contain a secreted alkaline phosphatase reporter gene for rapid viral quantitation, was cloned as a bacterial artificial chromosome, BA1, and then mutagenized to create recombinant viruses containing viral UL97 kinase sequence variants found in clinical specimens after ganciclovir treatment, but with no phenotypic data to determine their role in drug resistance. Seven control strains and 14 other recombinant strains were phenotyped for ganciclovir resistance and compared with similar strains created using prior technology to show a good concordance of findings. Sequence changes V466M, H469Y, A478V, N510S, A588V, K599R, L600I, G623S, T659I, and V665I were found to confer no significant ganciclovir resistance, while mutations L405P, M460T, A594E, and C603R conferred 3-to 9-fold increases in ganciclovir 50% inhibitory concentrations. Different mutations at codons 594 (A594V, A594E) and 603 (C603W, C603S) conferred varied amounts of ganciclovir resistance. Advances in recombinant phenotyping make it easier to show that many uncharacterized UL97 sequence variants do not confer ganciclovir resistance, but some are newly confirmed as resistance associated, including one (L405P) which is outside the codon range where such mutations are usually found. This information should improve the interpretation of genotypic data generated by diagnostic laboratories.

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“…e optimal duration of CMV prophylaxis is unknown, but in general, the longer the duration of prophylaxis, the lower the incidence of primary or recurrent CMV disease. is has been demonstrated in kidney transplant recipients aer six months of CMV prophylaxis with valganciclovir [19], and in recent studies by Humar and Zamora et al [20,21], it has been demonstrated that a longer duration of prophylaxis is bene�cial. However, it is not clear how much exposure to ganciclovir is required for effective prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Valganciclovir for CMV Prophylaxis after Lung Transplantation

Khurana

Kole

Falk

et al. 2013

ISRN Transplantation

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properly cited.Purpose. Cytomegalovirus (CMV) remains an important pathogen following solid organ transplantation (SOT). Universal prophylaxis for CMV is adopted by most centers aer lung transplantation. Various combinations studied for CMV prophylaxis include intravenous and oral ganciclovirs, oral valganciclovir, and CMV immunoglobulins. We present our experience with a low-dose of oral valganciclovir for CMV prophylaxis following lung transplantation. Methods and Materials. Our center started using 450 mg of daily oral valganciclovir for CMV prophylaxis in lung transplant recipients in Jan, 2001. A retrospective chart analysis of patients who underwent lung transplantation from January 2001 to December 2006 was done. Of 46 patients, 4 were excluded as they died within 30 days of transplant from postop complications. e mean age at transplant was 64 years, mostly single lung transplants (36/6) with a male-to-female ratio of 25/17. COPD was the most common reason for transplant (65%), and the serological CMV status of donors (D) and recipients (R) was as follows: D+/R+ 28, D+/R− 5, D−/R+ 5, and D−/R− 4. Valganciclovir was given for a total of 6 months posttransplant except for D−/R+ patients who received it for 12 months. Results. Five patients (12%) developed CMV disease with an average followup of 26 months. Only 2 (4.7%) developed CMV disease within six months of completing valganciclovir prophylaxis. is incidence is not signi�cantly different from the best-reported results of CMV prophylaxis in lung transplant recipients. e remaining 3 patients developed the disease later in their course, one as late as 32 months posttransplant. e main side effects noted include leucopenia, neutropenia, and GI disturbances. However, the number of patients who had to temporarily stop or discontinue the medication (9.5%) was signi�cantly lower than that reported in previous studies. Conclusions. Our experience suggests that low-dose valganciclovir is an effective method of prophylaxis for CMV disease in high-risk patients. It is a simple regimen that seems to have a better side effect pro�le and to improve patient compliance.

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A Trial of Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Lung Transplant Recipients

Abstract: Cytomegalovirus (CMV) infection is common after lung transplantation. We performed a prospective trial of valganciclovir prophylaxis in lung recipients

Cited by 90 publications

References 24 publications

Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

Cytomegalovirus Pneumonitis Is a Risk for Bronchiolitis Obliterans Syndrome in Lung Transplantation

Recombinant Phenotyping of Cytomegalovirus UL97 Kinase Sequence Variants for Ganciclovir Resistance

Low-Dose Valganciclovir for CMV Prophylaxis after Lung Transplantation

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