Associations of serum EBV DNA and gammopathy with post‐transplant lymphoproliferative disease

Rosselet, Anne; Vu, Dinh-Hao; Meylan, Pascal; Chaubert, Audrey S. Baur; Schapira, Marc; Pascual, Manuel; Aubert, Vincent; Tissot, Jean‐Daniel; Duchosal, Michel A.

doi:10.1111/j.1399-0012.2008.00904.x

Cited by 18 publications

(10 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This pattern was observed in Group 1, where EBV DNA loads appeared to be correlated with disease status. We found similar EBV DNA loads to those previously reported, with most studies showing EBV DNA concentrations ranging from 5.0 × 10 2 to 2.0 × 10 7 copies/ml in whole blood, plasma and serum [37,49,50]. EBV DNA was also detected in CSF at concentrations comparable to plasma, however detectable CSF EBV DNA has been previously reported only in association with acquired immunodeficiency syndrome (AIDS)-related brain lymphoma [51].…”

Section: Discussionsupporting

confidence: 88%

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

Lay

Lucas

Ratnamohan

et al. 2010

Virol J

View full text Add to dashboard Cite

BackgroundReactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample.ResultsEBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 102 to 1.3 × 108 copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 103 to 2.0 × 105 copies/ml in infectious mononucleosis (n = 7), 7.5 × 104 to 1.1 × 105 copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 102 to 5.6 × 103 copies/ml in HIV-infected patients (n = 12), and 2.0 × 102 to 9.1 × 104 copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11).ConclusionTwo sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.

show abstract

Section: Discussionsupporting

confidence: 88%

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

Lay

Lucas

Ratnamohan

et al. 2010

Virol J

View full text Add to dashboard Cite

show abstract

“…MGUS is considered to be a marker of B cell dysfunction after transplantation. It has been shown that MGUS after HSCT is associated with poor EBV-control and post-transplant lymphoproliferative disease (PTLD) [29, 30], which was also observed in one MGUS patient of our study cohort (patient 7). The other MGUS patient investigated (patient 6) suffered from GvHD, which has been associated with the presence of MGUS likewise [31].…”

Section: Discussionsupporting

confidence: 71%

VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation

et al. 2017

View full text Add to dashboard Cite

After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals. Interestingly, clonally related sequences were present in pre- and post-transplantation bone marrow of patients undergoing HSCT for acute myeloid leukemia treatment. We consistently observed such related B cell clones, irrespective of conditioning regimen, donor source or time post transplantation. In general, repertoire diversity was lower in post-HSCT as compared to pre-HSCT samples. However, post-HSCT repertoires retained highly mutated sequences, despite immunosuppressive therapy and presence of T cell deficiency after HSCT. These observations identify key properties of the recovering B cell compartment and provide a conceptual framework for the surveillance of humoral immunity after allogeneic transplantation.

show abstract

“…While most lymphomas developed in patients who received GOL 100 mg, as reported 7 , this may be expected given the possibility of dose escalation from 50 mg to 100 mg in patients with persistently active disease and the longer exposure of a greater number of patients to the 100-mg dose. Only 2 patients with lymphoma had evidence of EBV infection, which is noteworthy because the rate of EBV infection is higher among patients with lymphoma associated with immunosuppressive therapy than among patients with other lymphomas 34 . While lymphoma is a known, albeit infrequent, AE that was observed in these studies that were not powered to detect statistical significance of the differential rates of rare AE across dose groups, the potential development of lymphoma with higher doses of GOL requires continued pharmacovigilance.…”

Section: Variablesmentioning

confidence: 98%

Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

et al. 2016

View full text Add to dashboard Cite

OBJECTIVE: Assess 5-year golimumab (GOL) safety in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). METHODS: Subcutaneous (SC) GOL (50 mg or 100 mg every 4 weeks) was evaluated in phase 3 trials of patients with active RA, PsA, and AS. Safety data through Year 5 were pooled across 3 RA trials [1 each evaluating methotrexate (MTX)-naive, MTX-experienced, and antitumor necrosis factor (TNF)-experienced patients], 1 PsA trial, and 1 AS trial. Data summarized was derived from both placebo-controlled (through weeks 24-52) and uncontrolled study periods. For adverse events (AE) of special interest [serious infections (SI), opportunistic infections (OI), deaths, malignancies, demyelination, tuberculosis (TB)], incidence per 100 patient-years (pt-yrs) was determined. RESULTS: Across all trials, 639 patients received placebo and 2228 received SC GOL 50 mg only (n = 671), 50 mg and 100 mg (n = 765), or 100 mg only (n = 792). Safety followup extended for averages of 28.5 and 203.2 weeks for placebo and GOL, respectively. Respective placebo and GOL AE incidence/100 pt-yrs (95% CI) through Year 5 were 4.86 (2.83-7.78) and 3.29 (2.92-3.69) for SI, 0.00 (0.00-0.86) and 0.23 (0.14-0.35) for TB, 0.00 (0.00-0.86) and 0.22 (0.13-0.34) for OI, 0.00 (0.00-0.86) and 0.10 (0.05-0.20) for lymphoma, 0.00 (0.00-0.86) and 0.08 (0.03-0.17) for demyelination, and 0.29 (0.01-1.59) and 0.41 (0.29-0.57) for death. TB, OI, lymphoma, and demyelination incidence appeared to be higher among patients receiving GOL 100 mg only. CONCLUSION: SC GOL safety through Year 5 remained consistent with previously reported Year 3 findings and with other TNF antagonists. Numerically higher incidences of TB, OI, lymphoma, and demyelination were observed with 100 mg versus 50 mg. Clinicaltrials.gov identifiers: NCT00264537 (GO-BEFORE), NCT00264550 (GO-FORWARD), NCT00299546 (GO-AFTER), NCT00265096 (GO-REVEAL), and NCT00265083 (GO-RAISE)

show abstract

Associations of serum EBV DNA and gammopathy with post‐transplant lymphoproliferative disease

Abstract: Our results confirm an association between EBV in sera and gammopathy with PTLD, and highlight the high specificity of the former analysis. Whether a combination of both analyses will improve the clinical detection of PTLD remains to be evaluated in a larger prospective cohort study.

Cited by 18 publications

References 48 publications

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

VH1 Family Immunoglobulin Repertoire Sequencing after Allogeneic Hematopoietic Stem Cell Transplantation

Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Contact Info

Product

Resources

About