Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT

Esser, Joost W. J. van; Holt, Bronno van der; Meijer, Ellen; Niesters, Hubert G. M.; Trenschel, Rudolf; Thijsen, Steven; Loon, Anton M. van; Frassoni, Francesco; Bacigalupo, Andrea; Schaefer, U. W.; Osterhaus, Albert D. M. E.; Gratama, Jan W.; Löwenberg, Bob; Verdonck, Leo F.; Cornelissen, Jan J.

doi:10.1182/blood.v98.4.972

Cited by 341 publications

(316 citation statements)

References 62 publications

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“…Measuring EBV DNA has since been studied extensively and is now an indispensable tool for controlling PTLD. This method is used not only for diagnosis, but also for disease prediction [33,34,[58][59][60], therapeutic efficacy estimation [61,62], and prevention [63][64][65][66]. There has been debate regarding which specimen(s) should be used to identify PTLD.…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

“…Recent studies have used plasma or serum because they are readily obtained and handled. Several studies reported that quantifying cell-free EBV DNA predicted the development of PTLD [59,68,69]. However, serum or plasma samples lack cell-associated virus and therefore plasma loads are not correlated with PBMC values [70].…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

“…The overall incidence of PTLD is relatively low in stem cell transplantation (<1%), although T-celldepleted transplants or the use of anti-thymocyte globulin greatly increases the risk of PTLD. The high EBV load has some positive predictive and a very good negative predictive value, particularly if the graft was T-cell depleted [59,75]. Most transplantation facilities now monitor EBV load with real-time PCR for high-risk patients undergoing stem cell transplantation [3].…”

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

See 2 more Smart Citations

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

137

142

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Because Epstein-Barr virus (EBV) is ubiquitous and persists latently in lymphocytes, simply detecting EBV is insufficient to diagnose EBV-associated diseases. Therefore, measuring the EBV load is necessary to diagnose EBVassociated diseases and to explore EBV pathogenesis. Due to the diverse biology of EBV, the significance of measuring EBV DNA and the optimal type of specimen differ among EBV-associated diseases. Recent advances in molecular technology have enabled the EBV genome to be quantitated rapidly and accurately. Real-time polymerase chain reaction (PCR) is a rapid and reliable method to quantify DNA and is widely used not only as a diagnostic tool, but also as a management tool for EBV-associated diseases. However, each laboratory currently measures EBV load with its own ''homebrew'' system, and there is no consensus on sample type, sample preparation protocol, or assay units. The EBV real-time PCR assay system must be standardised for large-scale studies and international comparisons.

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Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

Section: Post-transplant Lymphoproliferative Disordermentioning

confidence: 99%

See 1 more Smart Citation

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Kimura

Ito

Suzuki

et al. 2008

Reviews in Medical Virology

137

142

View full text Add to dashboard Cite

show abstract

“…Several authors have reported a significantly increased EBV load at the time of diagnosis of post-transplant lymphoproliferative disease, up to 4log 10 higher than in control groups [Bai et al, 1997;Riddler et al, 1994;Rowe et al, 1997;Meerbach et al, 2001]. A rapid increase in peripheral blood EBV DNA load diagnosed and predicted posttransplant lymphoproliferative disease [Stevens et al, 2001a;Van Esser et al, 2001a;Orentas et al, 2003].…”

Section: Ebv Serostatusmentioning

confidence: 99%

Monitoring of Epstein‐Barr virus load after hematopoietic stem cell transplantation for early intervention in post‐transplant lymphoproliferative disease

Meerbach

Wutzler

Häfer

et al. 2008

Journal of Medical Virology

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Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease is a lifethreatening complication following hematopoietic stem cell transplantation. A quantitative polymerase chain reaction to evaluate EBV-genome copy numbers based on a nested polymerase chain reaction and an end-point dilution was used. Applying this assay EBV load was prospectively screened weekly in 123 patients after transplantation. The results demonstrate that EBV reactivations with more than 1,000 EBV-genome copies measured in 10(5) peripheral blood mononuclear cells were observed in 31 patients (25.2%). Three patients developed lymphoproliferative disease with extremely high EBV-genome copies in peripheral blood mononuclear cells (>100,000 copies/10(5) cells) and plasma. After combined antiviral and immune therapy two of three patients showed a dramatic decrease of EBV load and survived, while the third patient died of lymphoma. A subclinical EBV reactivation was observed in 24 cases (19.5%) with EBV-genome copies in 10(5) peripheral blood mononuclear cells ranging between 2,500 and mostly 10,000. After reduction of immunosuppression the EBV levels normalized. In four patients, the high copy number of > or =80,000 copies/10(5) peripheral blood mononuclear cells and plasma positivity prompted us to start pre-emptive therapy with rituximab and cidofovir for prevention of lymphoproliferative disease. After drug administration the high EBV load was reduced remarkably. Ninety-two patients (74.8%) who had < or =1,000 copies/10(5) peripheral blood mononuclear cells did not develop EBV-associated lymphoproliferative disease. In conclusion, monitoring of EBV load is a sensitive and useful parameter in the surveillance of EBV reactivation for early intervention in EBV-associated lymphoproliferative disease as well as for follow-up of the efficacy of therapy. Applying this assay EBV load was prospectively screened weekly in 123 patients after transplantation. The results demonstrate that EBV reactivations with more than

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“…Frequent molecular monitoring of the EBV load and anti-CD20 antibody therapy for cases at high risk have been suggested. [12][13][14] To further determine the incidence, outcome, risk profiles and clinical characteristics of EBV reactivations and PTLD in the post transplant period, we here performed a retrospective study in all 854 patients who received allogeneic SCT between January 1999 and June 2007 in the University Hospital of Hamburg, Germany, and performed further characterization of the 11 cases with EBV-associated PTLD and of the 15 cases with EBV reactivation.…”

Section: Introductionmentioning

confidence: 99%

EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT

Ocheni

Kroeger

Zabelina

et al. 2008

Bone Marrow Transplant

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Fatal problems encountered in allogeneic stem cell transplantation include EBV reactivation and post transplant lymphoproliferative disorders (PTLDs) with high mortality rates. We performed a retrospective analysis in all consecutive adult and pediatric EBV reactivations and PTLD during a period of 8.5 years. There were 26 patients with EBV reactivation/PTLD out of a total of 854 transplantations giving an overall incidence of 3.0%. Specifically, the incidence of EBV-PTLD was 1.3%, whereas that of EBV reactivation was 1.8%. Median age was 46.0 and 11.0 years in the adult and pediatric patients, respectively. There were high rates (54%) of concomitant bacterial, viral, fungal and parasitic infections at the time of EBV manifestation. Variable treatment regimens were applied including in most cases an anti-CD20 regimen often in combination with virustatic compounds, polychemotherapy or donor lymphocytes. The mortality rates were 9 of 11 (82%) in patients with EBV-PTLD and 10 of 15 (67%) in patients with reactivation. Only 7 of 26 patients (27%) are alive after a median follow-up of 758 days (range 24-2751). The high mortality rates of EBV reactivation and of EBV-PTLD irrespective of multimodal treatment approaches emphasize standardization and optimization of post transplant surveillance and treatment strategies to improve control of these often fatal complications.

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Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT

Abstract: Reactivation of the Epstein-Barr virus (EBV)after

Cited by 341 publications

References 62 publications

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Measuring Epstein–Barr virus (EBV) load: the significance and application for each EBV‐associated disease

Monitoring of Epstein‐Barr virus load after hematopoietic stem cell transplantation for early intervention in post‐transplant lymphoproliferative disease

EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT

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