A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Bueltzingsloewen, A Sirvent-von; Morand, Patrice; Buisson, Marlyse; Souillet, G; Chambost, Hérvè; Bosson, Jean‐Luc; Bordigoni, Pierre

doi:10.1038/sj.bmt.1703331

Cited by 23 publications

(37 citation statements)

References 47 publications

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“…For protection they were given immunoglobulins after transplantation resulting in high IgG antibody titers against virus capsid antigen and nuclear antigen of EBV. [Kenagy et al, 1995;Martinez et al, 1995;Bai et al, 1997;Rowe et al, 1997;Brengel-Pesce et al, 2002;Gärtner et al, 2002;Sirvent-von Bueltzingsloewen et al, 2002]. High amounts of EBV in peripheral blood mononuclear cells were detected in these patients [Savoie et al, 1994;Rooney et al, 1995;Lucas et al, 1998].…”

Section: Ebv Serostatusmentioning

confidence: 99%

“…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%

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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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Section: Ebv Serostatusmentioning

confidence: 99%

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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“…daclizumab, pentostatin) have not been evaluated in large studies. Sirvent-von Bueltzingsloewen et al 28 reported that a rapid increase in viral burden was a better predictor of disease onset than simply exceeding an absolute PCR threshold. Other groups have not clearly corroborated this experience, 9,24 but the rate of rise has not been adequately evaluated as a potential harbinger of PTLD.…”

Section: Future Directions and Unanswered Questionsmentioning

confidence: 99%

“…Furthermore, these values overlap significantly with PCR values from patients who did not develop PTLD. 9,12,28,32 Finally, the threshold PCR values used to define patients at risk for PTLD were established by retrospectively analyzing single-institution experiences and have, for Table 1 A comparison of published studies using polymerase chain reaction (PCR) for measuring Epstein-Barr viral load in the peripheral blood of HSCT recipients, either prior to the clinical presentation of PTLD (above) or at the time of presentation (below)…”

Section: Potential Shortcomings Of the Preemptive Pcr Approachmentioning

confidence: 99%

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Preemptive diagnosis and treatment of Epstein–Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development

Weinstock

Ambrossi

Brennan

et al. 2006

Bone Marrow Transplant

103

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Hematopoietic stem cell transplant (HSCT) recipients are at risk for Epstein-Barr virus (EBV)-associated, post transplant lymphoproliferative disorder (PTLD). Studies have suggested that early treatment may improve the outcome of patients with PTLD. Thus, significant attention has been focused on PCR-based approaches for preemptive (i.e., prior to clinical presentation) diagnosis. Reports from several transplant centers have demonstrated that HSCT recipients with PTLD generally have higher concentrations of EBV DNA in the peripheral blood than patients without PTLD. However, the PCR values of patients with PTLD typically span multiple orders of magnitude and overlap significantly with values from patients without PTLD. Thus, questions remain about the sensitivity and predictive value of these assays. Preemptive strategies using rituximab and/or EBVspecific cytotoxic T lymphocytes have been evaluated in patients with elevated EBV viral loads. We review the current literature, discuss our institutional experience and identify several areas of future research that could improve the diagnosis and treatment of this life-threatening disorder in HSCT recipients. Bone Marrow Transplantation ( EBV is associated with a spectrum of clinical presentations in hematopoietic stem cell transplant (HSCT) recipients, from fever to post transplant lymphoproliferative disorder (PTLD), which arise from the outgrowth of latently infected B cells in the absence of competent immune surveillance by cytotoxic T cells. PTLDs are extremely heterogeneous, ranging from polyclonal hyperplasia to aggressive, non-Hodgkin's lymphoma. 1-3 Thus, PTLD can present with a diverse spectrum of clinical symptoms and signs, most notably a sepsis-like syndrome with rapidly progressive lymphoma or a mononucleosis-like illness with fever, enlarged tonsils and/or cervical lymphadenopathy. PTLD may involve virtually any organ system, including the central nervous system, bone marrow, intestine and lungs. The overall frequency of PTLD after allogeneic HSCT is approximately 1%. The highest incidence occurs in the first 6 months after transplant, and the vast majority of cases develop during the first year. 4 Risk factors for PTLDMultiple published studies 4-10 have identified predisposing factors for PTLD, including in vivo and in vitro T-cell depletion. In a survey of 235 transplant centers, 4 the risk factors for PTLD in the first year after transplant included: (1) unrelated or HLA-mismatched donors (relative risk (RR) ¼ 4.1), (2) T-cell depletion (RR ¼ 12.7) and (3) the use of antithymocyte globulin (ATG) (RR ¼ 6.4) or anti-CD3 monoclonal antibodies (RR ¼ 43.2) for the prophylaxis or treatment of graft rejection and/or graft-versus-host disease (GVHD). PTLD occurred in 8% of HSCT recipients with two risk factors and 22% of recipients with three risk factors. For patients more than 1 year after HSCT, the only factor associated with PTLD was chronic GVHD (RR ¼ 4).Consistent with the essential role of T cells in controlling the proliferation of latent EBV-inf...

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Prevention and Treatment of Epstein—Barr Virus Associated Lymphoproliferative Disorders in Recipients of Bone Marrow and Solid Organ Transplants

Meijer¹,

Dekker²,

Weersink³

et al. 2003

ChemInform

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A prospective study of Epstein–Barr virus load in 85 hematopoietic stem cell transplants

Cited by 23 publications

References 47 publications

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

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

Preemptive diagnosis and treatment of Epstein–Barr virus-associated post transplant lymphoproliferative disorder after hematopoietic stem cell transplant: an approach in development

Prevention and Treatment of Epstein—Barr Virus Associated Lymphoproliferative Disorders in Recipients of Bone Marrow and Solid Organ Transplants

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