Early detection of cytomegalovirus (CMV) infection in bone marrow transplant patients by reverse transcription-PCR for CMV spliced late gene UL21.5: a two site evaluation

Boriskin, Yu. S.; Fuller, Katherine; Powles, R; Vipond, Ian B.; Rice, Philip; Booth, James C.; Caul, E.O.; Butcher, Philip D.

doi:10.1016/s1386-6532(01)00209-8

Cited by 18 publications

(9 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Not all of the studies described above are included, due to varying study designs and end points or lack of clinical data (1,9,10,26,40). In several papers the sensitivity, specificity, positive predictive value, and negative predictive value of the experimental assay(s) were calculated.…”

Section: Discussionmentioning

confidence: 99%

“…In several papers the sensitivity, specificity, positive predictive value, and negative predictive value of the experimental assay(s) were calculated. In those studies the gold standard to calculate these values was defined as CMV reactivation based on positive results from Ag and/or PCR assays (1,10,40). In our view, a surveillance method for CMV reactivation should be judged on its clinical merits, with the incidences of CMV disease and transplant-related mortality being the most significant end points.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

2003

View full text Add to dashboard Cite

The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8+ cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 × 106 to 20 × 106 CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8+ T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

2003

View full text Add to dashboard Cite

show abstract

“…To avoid a lethal outcome of CMV disease, the start of treatment at the earliest stage is of extreme significance (3,8). The level of CMV DNA has been found to be an important prognostic marker for the ongoing disease (1,2,4).…”

mentioning

confidence: 99%

Detection of Cytomegalovirus (CMV) DNA in EDTA Whole-Blood Samples: Evaluation of the Quantitative artus CMV LightCycler PCR Kit in Conjunction with Automated Sample Preparation

et al. 2008

View full text Add to dashboard Cite

Whole blood has been found to be a reliable matrix for the detection and quantitation of cytomegalovirus (CMV) DNA. In this study, the performance of the artus CMV LightCycler (LC) PCR kit in conjunction with automated sample preparation on a BioRobot EZ1 workstation was evaluated. The accuracy, linearity, analytical sensitivity, and inter-and intra-assay variations were determined. A total of 102 clinical EDTA whole-blood samples were investigated, and results were compared with those obtained with the in vitro diagnostics (IVD)/Conformité Européene (CE)-labeled CMV HHV6,7,8 R-gene quantification kit. When the accuracy of the new kit was tested, seven of eight results were found to be within ؎0.5 log 10 unit of the expected panel results. Determination of linearity resulted in a quasilinear curve over more than 5 log units. The lower limit of detection of the assay was determined to be 139 copies/ml in EDTA whole blood. The interassay variation ranged from 15 to 58%, and the intra-assay variation ranged from 7 to 35%. When clinical samples were tested and the results were compared with those of the routinely used IVD/CE-labeled assay, 53 samples tested positive and 13 samples tested negative by both of the assays. One sample was found to be positive with the artus CMV LC PCR kit only, and 35 samples tested positive with the routinely used assay only. The majority of discrepant results were found with low-titer samples. In conclusion, use of the artus CMV LC PCR kit in conjunction with automated sample preparation on the BioRobot EZ1 workstation may be suitable for the detection and quantitation of CMV DNA in EDTA whole blood in the routine low-throughput laboratory; however, low-positive results may be missed by this assay.

show abstract

“…HCMV may be detectable in blood samples of patients with asymptomatic infection, who never progress to disease, because of the high sensitivity of real time PCR [32]. In addition, as PCR of blood requires 247-1650 copies of HCMV DNA per ml and 500 DNA copies per 100 ng of total leucocytes, DNA is equivalent to 10,000 cells [33], the identification of HCMV before engraftment (usually before day +30) limits early HCMV diagnosis. Thus, the identification of HCMV in the saliva could be advantageous to the diagnosis of reactivation of this virus in the period before engraftment.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Production and Human Cytomegalovirus Load in Allogeneic Hematopoietic Stem Cell Transplantation Outcome

TA¹

2016

Int J Immunother Cancer Res

View full text Add to dashboard Cite

Objective: To investigate the impact of cytokine levels (IL-1β, IL-6, IL-10, IFN-γ and TNF-α) and Human cytomegalovirus (HCMV) load in the saliva and blood on the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Study Design: Samples were obtained from 63 patients 7 days before and 21 days after allo-HSCT. Cytokine levels were assessed by ELISA, and HCMV load was determined by real-time PCR. Results:The increase of IL-6 in the saliva and the reduction of IFN-γ in the blood before allo-HSCT were associated with increased risk of death. Moreover, the increase of IL-6 in the blood and of HCMV in the saliva after allo-HSCT were also associated with increased risk of death. Conclusions:Cytokine levels and HCMV load were associated with the increased risk of death. The findings suggest a potential function of these biomarkers in the determination of allo-HSCT survival.factor-α (TNF-α) and interleukin-1 (IL-1), could be increased as a result of disease, therapy, comorbidities or ongoing infections that occur before allo-HSCT. Second, immediately after allo-HSCT, the immune dysfunction caused by the conditioning regimen, which may produce tissue injury and consequently the production of inflammatory cytokines, may affect the reconstitution of white blood cells. Third, after allo-HSCT, activated, mature donor T-cells can set off a cytokine response that in turn stimulates host T-cell responses related to the onset of acute graft-versus-host disease (aGVHD) [3,4]. Immune dysfunction following allo-HSCT involves activated T-cells secreting interferon (IFN)-γ as well as other cytokines, which activate monocytes and dendritic cells. This process appears to be associated with the induction of aGVHD, resulting in significant morbidity and mortality. In addition, a prolonged immune deficiency characterized by lymphopenia and susceptibility to infection can occur [2]. Deregulation of inflammatory cytokines is also associated with multiple symptoms (pain, sleep disturbance and depression) during neutropenia after allo-HSCT [3]. Interleukin-6 (IL-6) is an important pro-inflammatory cytokine involved in immune-mediated complications after allo-HSCT [5].Human cytomegalovirus (HCMV) infection remains one of the most important causes of morbidity and mortality among allo-HSCT recipients [6,7]. Infection by HCMV may result not only in HCMV disease, but is also associated with other adverse effects due to its immunomodulatory actions; this might result in increased risk of bacterial, fungal and viral infections, and also of aGVHD [8].Allo-HSCT outcomes could be affected by factors such as HCMV infection, recipient/donor histocompatibility, patient/donor gender,

show abstract

Early detection of cytomegalovirus (CMV) infection in bone marrow transplant patients by reverse transcription-PCR for CMV spliced late gene UL21.5: a two site evaluation

Cited by 18 publications

References 42 publications

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

Detection of Cytomegalovirus (CMV) DNA in EDTA Whole-Blood Samples: Evaluation of the Quantitative artus CMV LightCycler PCR Kit in Conjunction with Automated Sample Preparation

Cytokine Production and Human Cytomegalovirus Load in Allogeneic Hematopoietic Stem Cell Transplantation Outcome

Contact Info

Product

Resources

About