Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

Boersma, Marijke Nynke; Zanden, Adri van der; Laverman, Gozewijn D.; Sanders, Jan-Stephan; Vries, P A M de

doi:10.1111/j.1432-2277.2012.01552.x

Cited by 15 publications

(14 citation statements)

References 23 publications

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“…Should we consider changing asymptomatic individuals with high-level EBV DNAemia to MMF, and should low-dose MMF with steroids be the maintenance agents of choice in new cases of EBV positive PTLD, rather than low-dose calcineurin inhibitors? PTLD risk registry analyses suggest that MMF-treated individuals overall may have a reduced incidence and risk of PTLD development (23)(24)(25)(26), although recent analyses report a high prevalence of MMF use in primary central nervous system PTLD (27,28). To date there is no clear evidence to guide immunosuppression prescribing in the late posttransplant period as treatment or prevention of EBV-related disease or PTLD.…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that this may be due to an anti-B cell effect, reducing the EBV-carrying B lymphocyte population (18). Treatment with rituximab is associated with transient depletion of B cell numbers with corresponding falls in EBV viral loads, and studies have also reported subsequent rises in viral loads as B cell numbers are later reconstituted (6,21,22 (27,28). To date there is no clear evidence to guide immunosuppression prescribing in the late posttransplant period as treatment or prevention of EBV-related disease or PTLD.…”

Section: Bamoulid Et Al Holman Et Al and Holmes Et Al Reported Ebvmentioning

confidence: 99%

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Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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Epstein-Barr virus (EBV) DNAemia in the first year posttransplantation has been studied extensively. There is a paucity of information on prevalence and sequelae of EBV infection in adult renal transplantation beyond the first year. This single-center study examines the relationship between EBV DNAemia and demographic, immunosuppressive, hematologic and infection-related parameters in 499 renal transplant recipients between 1 month and 33 years posttransplant. Participants were tested repeatedly for EBV DNAemia detection over 12 months and clinical progress followed for 3 years. Prevalence of DNAemia at recruitment increased significantly with time from transplant. In multivariate adjusted analyses, variables associated with DNAemia included EBV seronegative status at transplant (p ¼ 0.045), nonWhite ethnicity (p ¼ 0.014) and previous posttransplant lymphoproliferative disease (PTLD) diagnosis (p ¼ 0.006), while low DNAemia rates were associated with mycophenolate mofetil use (p < 0.0001) and EBV viral capsid antigen positive Epstein-Barr nuclear antigen-1 positive serostatus at transplant (p ¼ 0.044). Patient and graft survival, rate of kidney function decline and patient reported symptoms were not significantly different between EBV DNAemia positive and negative groups. EBV DNAemia is common posttransplant and increases with time from transplantation, but EBV DNAemia detection in low-risk (seropositive) patients has poor specificity as a biomarker for future PTLD risk.

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Section: Discussionmentioning

confidence: 99%

Section: Bamoulid Et Al Holman Et Al and Holmes Et Al Reported Ebvmentioning

confidence: 99%

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Morton¹,

Coupes²,

Roberts

et al. 2014

American Journal of Transplantation

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“…Serological markers, such as increasing EBV load [26,27] or chemokine (C-X-C motif) ligand 13 (CXCL13) [28] and positron emission tomography with [18F]-2-fluoro-2-desoxy-glucose [29] may facilitate discrimination between PTLD and other posttransplant complications, but these methods have a much lower specificity and sensitivity than histology and are therefore not applicable for primary diagnostics. Furthermore, serological markers are mainly analyzed in extracranial PTLD, although cerebral manifestation can be associated with no detectable EBV in the peripheral blood but EBV positivity in the liquor [30,31]. …”

Section: Pathogenesis and Origin Of Ptldmentioning

confidence: 99%

Posttransplant Lymphoproliferative Disorder in Pediatric Patients

Hussein¹,

Tiede²,

Maecker‐Kolhoff³

et al. 2013

Pathobiology

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Transplantation of solid organs and hematopoietic stem cells is accompanied by profound disturbance of immune function mediated by immunosuppressive drugs or delayed immune reconstitution. Disturbed T cell control of Epstein-Barr virus (EBV)-infected B cells leads to posttransplant lymphoproliferative disorder (PTLD) in up to 10% of patients. Children are at a higher risk because they are more often EBV-naïve before transplantation. Patients with PTLD often present with unspecific symptoms (pain and organ/graft dysfunction). Depending on the onset of PTLD, manifestations vary between mainly nodal (late PTLD) and extranodal sites (early PTLD). Histology, immunohistology, EBER in situ hybridization and molecular pathology are required for diagnosis and subclassification of PTLD. The three major types are early lesions (resembling reactive proliferations in immunocompetent patients), polymorphic PTLD (proliferation of B and T cells with effacement of histoarchitecture) and monomorphic PTLD (presenting as malignant lymphomas, mainly high-grade B cell lymphomas). In a subfraction of cases, including monomorphic PTLD, reduction of immunosuppressive medication alone is sufficient to induce remission. Surgical debulking of tumor mass and anti-CD20-antibody treatment with or without chemotherapy (usually at lower dosages than in immunocompetent patients) constitute the basis of additional therapy.

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“…4 and 13, we did not detect elevated EBV load in the serum but rather in the CSF, indicating EBV‐associated CNS‐PTLD. In patients with CNS lesions, detection of EBV load in the serum can result in negative results ; therefore, examination of CSF samples is recommended . Furthermore, in patient no.…”

Section: Discussionmentioning

confidence: 99%

Post‐Transplant Lymphoproliferative Disorder in Kidney Transplant Recipients: A Single‐Center Experience in Japan

et al. 2016

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Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplantation; however, few large studies have been performed in Asian institutions. We review our single-center experience with post-transplant lymphoproliferative disorder patients in Japan. We retrospectively evaluated patients with post-transplant lymphoproliferative disorder following kidney transplantation between January 1985 and December 2013. The patients were divided into early-onset post-transplant lymphoproliferative disorder (<1 year) and late-onset post-transplant lymphoproliferative disorder (≥1 year) groups. Thirteen patients had the disorder, an incidence rate of 0.75% (13/1730). Early-onset post-transplant lymphoproliferative disorder (N = 3) had not occurred for the last two decades. In the late-onset group (N = 10), the median time of onset was 108.7 months. The Kaplan-Meier 10-year overall survival rates were 76.9% and 95.4% in patients with and without the disorder, respectively (P = 0.0001). Post-transplant lymphoproliferative disorder significantly affected transplant recipients' mortality. Late-onset occurred even > 10 years after transplantation; therefore, long-term monitoring of patients is needed.

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Epstein-Barr virus-positive post-transplant lymphoproliferative disorder of the central nervous system, after renal transplantation with a discrepancy in viral load between peripheral blood and cerebrospinal fluid

Cited by 15 publications

References 23 publications

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Epstein–Barr Virus Infection in Adult Renal Transplant Recipients

Posttransplant Lymphoproliferative Disorder in Pediatric Patients

Post‐Transplant Lymphoproliferative Disorder in Kidney Transplant Recipients: A Single‐Center Experience in Japan

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