CMV antigenemia and quantitative viral load assessments in hematopoietic stem cell transplant recipients

Cardeñoso, Laura; Pinsky, Benjamin A.; Lautenschlager, Irmeli; Aslam, Shagufta; Cobb, Bryan; Vilchez, Regis A.; Hirsch, Hans H.

doi:10.1016/j.jcv.2012.10.001

Cited by 29 publications

(21 citation statements)

References 13 publications

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“…Slides were analyzed using immunofluorescence microscopy and CMVpp65 antigen-positive cells were counted. Generally, CMVpp65 antigenemia results in immunofluorescence testing (IFT) correlate well with results for CMV-DNA in qPCR 25.…”

Section: Methodsmentioning

confidence: 92%

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Schmitt¹,

Schmitt²,

Wiesneth³

et al. 2017

Theranostics

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Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide.Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia. Flow cytometry for CMV-specific CD8+ and γδ T cells as well as neutralizing anti-CMV antibodies were correlated to clinical parameters.Results: The vaccination was well tolerated. Seven of nine patients cleared CMVpp65 antigenemia after four vaccinations and are still free from antigenemia to this day. Two patients with CMV reactivation showed persisting CMV antigenemia. One patient received prophylactic vaccination and did not develop antigenemia. An increase of up to six-fold in frequency of both CMV-specific CD8+ T cells and/or Vδ2negative γδ T cells was detected. Titers of neutralizing antibodies increased up to the tenfold. Humoral and cellular immune responses correlated with clearance of CMV.Conclusion: In summary, CMVpp65 peptide vaccination for patients after allogeneic stem cell transplantation at high risk for CMV reactivation was safe, well tolerated and clinically encouraging. A study in solid-organ transplant patients is ongoing.

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Section: Methodsmentioning

confidence: 92%

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Schmitt¹,

Schmitt²,

Wiesneth³

et al. 2017

Theranostics

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“…The availability of these controls will allow transplants centers to assess the performance of the methodologies used, and the results obtained will enable to define common guidelines for CMV pre-emptive therapy. 26,27 The methodology of real-time PCR showed an excellent performance for this population and must be performed routinely to monitor these patients. Nonetheless, besides the clinical benefit of replacement of pp65 CMV antigen detection by qPCR, it should be also considered its financial impact on the setting of HSCT in low-and middle-income countries, such as Brazil.…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus detection by real-time PCR and pp65-antigen test in hematopoietic stem cell transplant recipients: a challenge in low and middle-income countries

Breda

Almeida

Carstensen

et al. 2013

Pathogens and Global Health

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Aim: Cytomegalovirus (CMV) infection is one of the most common complications in patients submitted to hematopoietic stem cell transplant (HSCT). Pre-emptive therapy has been indicated in patients with laboratory evidence of CMV replication. The aims of this study were to compare real-time PCR or pp65 antigen assay methodologies to detect CMV replication in HSCT patients, define a viral load threshold for initiation of pre-emptive therapy, and assess the feasibility of its implementation in hospitals of countries with low and middle income. Material and methods: Human CMV detection by real-time PCR and pp65 antigen assay was carried out in blood and plasma samples of HSCT patients collected weekly during 3 months. Pre-emptive therapy was based on CMV antigenemia results. Results: Twenty-one patients were monitored with a total of 227 samples collected; 13 (62%) patients were children. A poor correlation was observed between qualitative results, though quantitative results showed statistically significant difference, with higher viral loads detected in patients with positive antigenemia. Compared to a positive antigenemia, a cutoff value of 1067.5 copies/ml, 3.03 log 10 /ml, for viral load was obtained with 100% sensitivity and 71% specificity. Conclusion: CMV real-time PCR in whole blood was suitable for monitoring HSCT patients. However, its high cost is a limiting factor, and it could be used to monitor selected patients, those with prolonged leukopenia and underweight children, and subsequently switched to pp65 antigen test. Further studies involving larger numbers of patients should be performed to confirm this statement.

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“…Preemptive therapy strategies involving virologic monitoring and early intervention with antiviral therapy have been widely employed and successful in reducing CMV disease(4, 5). Quantitative nucleic acid amplification techniques have largely replaced pp65 antigenemia for early CMV detection and off erimproved sensitivity without loss of specificity(6-8). Despite the widespread use of quantitative PCR, there is no consensus regarding the CMV level at which preemptive therapy should be initiated(9-11).…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

Waggoner

Pinsky

2015

Journal of Clinical Virology

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Background Preemptive antiviral therapy relies on viral load measurements and is the mainstay of cytomegalovirus (CMV) prevention in hematopoietic cell transplant (HCT) recipients. However, optimal CMV levels for the initiation of preemptive therapy have not been defined. Objectives To evaluate the relationship between plasma CMV DNA levels at initiation of preemptive therapy with time to resolution of viremia and duration of treatment. Study Design Retrospective analysis of HCT recipients undergoing serial CMV PCR testing between June 2011 and June 2014 was performed. Results 221 HCT recipients underwent preemptive therapy for 305 episodes of CMV viremia. Median time to resolution was shorter when treatment was initiated at lower CMV levels (15 days at 135-440 international units (IU)/mL, 18 days at 441-1000 IU/mL, and 21 days at >1000 IU/mL, P <.001). Prolonged viremia lasting >30 days occurred less frequently when treatment was initiated at 135-440 IU/mL compared to 441-1000 IU/mL and >1000 IU/mL (1%, 15%, 24%, P<.001). Median treatment duration was also shorter in the lower viral load groups (28, 34, 37 days, P <.001). Conclusion Initiation of preemptive therapy at low CMV levels was associated with shorter episodes of viremia and courses of antiviral therapy. These data support the utility of initiating preemptive CMV therapy at viral loads as low as 135 IU/mL in HCT recipients.

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CMV antigenemia and quantitative viral load assessments in hematopoietic stem cell transplant recipients

Cited by 29 publications

References 13 publications

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

Human cytomegalovirus detection by real-time PCR and pp65-antigen test in hematopoietic stem cell transplant recipients: a challenge in low and middle-income countries

Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients

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