Quantitative Polymerase Chain Reaction to Predict Occurrence of Symptomatic Cytomegalovirus Infection and Assess Response to Ganciclovir Therapy in Renal Transplant Recipients

Roberts, Thomas C.; Brennan, Daniel C.; Buller, Richard S.; Gaudreault‐Keener, Monique; Schnitzler, Mark A.; Sternhell, Kara E.; Garlock, Kathryn; Singer, Gary G.; Storch, Gregory A.

doi:10.1086/515383

Cited by 94 publications

(85 citation statements)

References 32 publications

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“…33 Assessment of viral load kinetics may provide a tool for stratifying risk profiles for HCMV disease and help reduce the considerable rate of antiviral overtreatment. Although a correlation between peak viral load and HCMV disease development was noticed by several other groups in patients after solid organ transplantation and HIV patients, 28,[34][35][36][37][38][39] discordant results have been reported in SCT patients. 15,16,22,31,40 For abbreviations, see Table 1 footnote.…”

Section: Discussionmentioning

confidence: 85%

Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Lengerke

Ljubicic

Meisner³

et al. 2006

Bone Marrow Transplant

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Early diagnosis of human cytomegalovirus (HCMV) infection and the introduction of preemptive antiviral therapy have reduced HCMV-related mortality after allogeneic stem cell transplantation. A critical goal remains stratifying risk profiles and minimizing potential harm owing to antiviral overtreatment. We compared the commercially available standardized COBAS Amplicor CMV Monitor (CACM) to an in-house PCR assay, for the monitoring of HCMV infection. Seventy-two patients were surveyed by an in-house PCR of whole blood, quantitative viral load assessment by CACM and virus culture assays in a prospective and a retrospective study. A high concordance between CACM and PCR was documented. The viral load at onset correlated with the peak viral load (Spearman rank correlation R ¼ 0.634, P ¼ 0.0004). In patients developing HCMV disease, both viral loads were in trend higher (P ¼ 0.823, respectively P ¼ 0.053), and the viremic episodes longer (P ¼ 0.015), as compared to asymptomatically HCMV-infected patients. The serological pre-transplant status was the major risk factor for the development of HCMV disease, showing highest risk for seropositive patients receiving a seronegative graft, whereas donor type (related or unrelated) and graft type (bone marrow or peripheral blood mobilized stem cells) did not have an influence. HCMV infection proved to be a risk factor for the development of non-viral opportunistic infections (P ¼ 0.002).

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Section: Discussionmentioning

confidence: 85%

Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Lengerke

Ljubicic

Meisner³

et al. 2006

Bone Marrow Transplant

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“…Similar conclusions have been drawn from recent studies involving other immunosuppressed cohorts. 38,[42][43][44][45][46][47][48][49][50] Quantitative PCR for CMV appears to be an effective diagnostic tool in identifying patients with disease. In addition, PCR detection of DNA targets is less sensitive to sample handling than other diagnostic tests.…”

Section: Predictive Value Of Quantitative Pcrmentioning

confidence: 99%

“…Similar results have been reported for other immunosuppressed populations. 34,36,45,46,50,55,70 Management of anti-CMV therapy using quantitative PCR could potentially reduce the incidence of therapy-related side effects and therapy costs if disease could be controlled with a more limited course of antiviral therapy. EBV levels were also found to respond to changes in medication in the patient with lympadenopathy.…”

Section: Predictive Value Of Quantitative Pcrmentioning

confidence: 99%

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Bai

Rogers

Harkins

et al. 2000

The Journal of Molecular Diagnostics

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Human herpesviruses can cause significant morbidity and mortality in pediatric solid organ transplant recipients. It was hypothesized that viral burden quantification by polymerase chain reaction using an internal calibration standard could aid in distinguishing between viral disease and latency. Here we report the results of a 2-year prospective study of 27 pediatric solid organ (liver, kidney, or heart) transplant recipients in which multiple samples were analyzed for levels of all eight human herpesviruses by internal calibration standard-polymerase chain reaction. Herpes simplex viruses 1 and 2, varicella-zoster virus, and Kaposi's sarcoma-associated herpesvirus were not detected in any of these samples. Human herpesvirus types 6 and 7 were detected in half of the patients, but were present at low levels, similar to those found in reference populations. Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were detected in 89% and 56% of the patients, respectively. Viral burden analysis suggested distinct patient populations for CMV, with a natural cutoff of 10,000 viral targets/ml blood strongly associated with disease. In some cases, a dramatic increase in CMV levels preceded clinical evidence of disease by several weeks. EBV viral burden was relatively high in the only patient presenting with an EBV syndrome. However, two other patients without evidence of EBV disease had single samples with high EBV burden. Rapid reduction in both EBV and CMV burden occurred with antiviral treatment. These data suggest that viral burden analysis using internal calibration standard-polymerase chain reaction for CMV, and possibly other herpesviruses, is an effective method for monitoring pediatric transplant patients for significant herpesvirus infection and response to therapy.

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“…There have been many studies evaluating the clinical utility of a PCR-based assay for detection of HCMV DNA. [19][20][21] Many of these investigations have shown that the assay may be sensitive but has not enough clinical specificity to detect HCMV in patients who do not have active HCMV disease. However, we demonstrated a significant association between double primer PCR assay results of PMN leukocytes and antigenemia results in relation to clinical status of BMT patients.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of a double primer PCR assay with plasma, leukocytes and antigenemia for diagnosis of active human cytomegalovirus infection in bone marrow transplant patients

Yaghobi

Behzad-Behbahani

Sabahi

et al. 2005

Bone Marrow Transplant

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Summary:The aim of the study was to determine the prognostic value of a double primer PCR assay to detect human cytomegalovirus (HCMV) infection or disease in bone marrow transplant (BMT) recipients. A total of 209 blood samples including peripheral blood mononuclear cells (PBMN), polymorphonuclear (PMN) leukocytes and plasma from 26 BMT recipients were tested by PCR assay. To discriminate between latent and active HCMV infection, 177 blood samples were also tested by a quantitative antigenemia assay. HCMV serology status of donors and recipients was determined before transplantation by an enzyme immunosorbent assay method. Using the double primer PCR assay, the number of positive samples increased by an average of 11.6%. Symptomatic active HCMV infection was diagnosed in 14 (53.8%) out of 26 BMT patients. There was a good association between double primer PCR assay of PMN leukocytes and antigenemia assays for detection of active HCMV infection in all patients. Detection of HCMV DNA in PMN leukocytes of BMT patients by double primer PCR assay can be an alternative method for antigenemia assay. However, quantitative PCR methods will be necessary for monitoring antiviral treatment. Bone Marrow Transplantation (2005) 35, 595-599.

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Quantitative Polymerase Chain Reaction to Predict Occurrence of Symptomatic Cytomegalovirus Infection and Assess Response to Ganciclovir Therapy in Renal Transplant Recipients

Cited by 94 publications

References 32 publications

Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Predictive Value of Quantitative PCR-Based Viral Burden Analysis for Eight Human Herpesviruses in Pediatric Solid Organ Transplant Patients

Comparative analysis of a double primer PCR assay with plasma, leukocytes and antigenemia for diagnosis of active human cytomegalovirus infection in bone marrow transplant patients

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