Prompt versus preemptive intervention for EBV lymphoproliferative disease

Wagner, Hans‐Joachim; Cheng, Yee Chung; Huls, M. Helen; Gee, Adrian P.; Kuehnle, Ingrid; Krance, Robert A.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.

doi:10.1182/blood-2003-12-4287

Cited by 212 publications

(173 citation statements)

References 16 publications

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“…This suggests that monitoring EBV DNAemia in the first 100 days is warranted, together with preemptive (at the time of high/rising EBV DNAemia) or prompt (early in the course of PTLD) administration of rituximab- [42][43][44] or EBV-specific T lymphocytes. 2,14,45,46 This is in support of current guidelines. 47,48 In our cohort, the PTLD-associated mortality was 2.3-3.9%.…”

Section: Discussionsupporting

confidence: 84%

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28-770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

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Section: Discussionsupporting

confidence: 84%

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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“…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%

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

135

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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“…between 200 copies/10 5 peripheral blood mononuclear cells , ≥300/10 5 peripheral blood mononuclear cells [Cesaro et al, 2004], >300/µg DNA [Sirvent-von Bueltzingsloewen et al, 2002], >10 2,5 /µg DNA [Hoshino et al, 2001], >500/75,000 peripheral blood mononuclear cells [Frias et al, 2001], >1,000/10 5 cells [Bacigalupo, 2005], >4,000/µg DNA [Wagner et al, 2004], 6,215/ml blood [Yancoski et al, 2004] and 10,000/µg DNA [Orentas et al, 2003]. As shown in Table 2, EBV load of >100,000 EBV-genome copies /10 5 peripheral blood mononuclear cells significantly predicts EBV lymphoproliferative disease in our study, whereas patients with ≤1,000 EBV-genome copies/10 5 peripheral blood mononuclear cells did not develop a lymphoproliferative disorder.…”

Section: Cut-offmentioning

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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Prompt versus preemptive intervention for EBV lymphoproliferative disease

Cited by 212 publications

References 16 publications

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

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

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