Posttransplant Lymphoproliferative Disease in Primary Epstein‐Barr Virus Infection after Liver Transplantation: The Role of Cytomegalovirus Disease

Máñez, Rafael; Breinig, Mary C.; Linden, Peter K.; Wilson, John W.; Cisneros, Julian Torre; Kusne, Shimon; Dummer, Stephen; Ho, Monto

doi:10.1086/514142

Cited by 236 publications

(157 citation statements)

References 20 publications

(8 reference statements)

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“…While in EBV-negative children who have undergone allogeneic BMT, development of PTLD may be associated with reactivation of EBV in donor cells, in solid organ transplantation, EBV-negative children have a higher incidence of PTLD. 17 For this case, it is not known whether this PTLD is associated with pri-mary EBV infection or reactivation since serologic tests were not performed prior to autologous PSCT. Also, the endoscopic biopsy specimens containing PTLD were not sufficient for additional special studies to evaluate EBV.…”

Section: Discussionmentioning

confidence: 97%

“…In solid organ transplant recipients, CMV infection has been reported to be associated with PTLD. 17 CMV infection indicates a significant level of immunosuppression and has been suggested to be additionally immunosuppressive and an increased risk factor for development of PTLD. 17 For this case report, it is not known whether this CMV infection represents a primary infection or reactivation since serologic tests were not performed prior to autologous PSCT.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient

Lones

Kirov

Said

et al. 2000

Bone Marrow Transplant

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Summary:Post-transplant lymphoproliferative disorder (PTLD) is a complication of allogeneic bone marrow transplantation (BMT). Rare cases of PTLD after autologous BMT have been reported only in adults. This case report is the first to describe PTLD in a pediatric patient after autologous peripheral stem cell transplantation (PSCT). This 2-year-old male with stage IV neuroblastoma underwent autologous PSCT. The post-PSCT course was complicated by fever with hematochezia and a lung mass. On day 94 post PSCT, colonoscopy revealed an ulcer due to a PTLD, monomorphic type, B cell phenotype, associated with Epstein-Barr virus. Fine needle aspiration identified the lung mass as neuroblastoma. PTLD can occur in pediatric autologous PSCT recipients, and may occur more frequently in autologous grafts manipulated by T cell depletion or CD34 + cell selection. Bone Marrow Transplantation (2000) 26, 1021-1024. Keywords: hematopoietic stem cell transplantation; autologous transplantation; lymphoproliferative disorders; herpesvirus; child Post-transplant lymphoproliferative disorder (PTLD) is a complication in bone marrow transplantation (BMT). 1 PTLD is more frequently associated with allogeneic BMT, particularly with immunosuppressive therapy for graft-versus-host disease or T cell-depleted marrow grafts. Autologous BMT or peripheral stem cell transplantation (PSCT) is less immunosuppressive than allogeneic BMT. There are only rare reports of PTLD following autologous BMT or PSCT, all of which occurred in adults. [2][3][4][5][6][7][8] This case report describes the first pediatric patient with an autologous PSCT to develop a PTLD associated with Epstein-Barr virus (EBV). Materials and methodsClinical information was obtained retrospectively from medical records. Endoscopic biopsy tissues were placed in Bouin's fixative and submitted for routine processing. Paraffin-embedded 4 m thick tissue sections were prepared and stained with hematoxylin-eosin for light microscopic evaluation. Paraffin section immunohistochemistry and EBV encoded RNA (EBER) in situ hybridization studies were performed using previously described methods. 9 Positive controls for EBER in situ hybridization and EBV latent membrane protein (LMP-1) immunohistochemistry stains included sections from a lymph node biopsy containing mixed cellularity Hodgkin's disease prepared with Bouin's fixative which demonstrated appropriate staining of ReedSternberg cells. PTLD was classified using previously described criteria. 10 Case historyA male child presented at age 21 months with stage IV neuroblastoma involving the left adrenal gland, left neck and axillary lymph nodes, and the right orbit. He was treated according to the Memorial Sloan-Kettering Protocol 7 with a total of six cycles of chemotherapy consisting of cyclophosphamide/vincristine/adriamycin alternated with cisplatin/VP-16. Six months after diagnosis, the adrenal mass was completely resected, followed by resection of the residual left neck mass, which demonstrated neuroblastoma. One month later, an autolog...

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient

Lones

Kirov

Said

et al. 2000

Bone Marrow Transplant

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“…Risk factors that favor the development of PTLD include pretransplantation EBV seronegativity 2 ; type, intensity, and duration of immunosuppression 3 ; and cytomegalovirus disease. 2,4 Thus, a greater incidence than previously reported is present in pediatric recipients of cadaveric organs because the majority of individuals aged younger than 14 years are likely to be EBV naive. In addition, graft rejection or infection that leads to the production of inflammatory cytokines or stress situations will ultimately favor reactivation of herpes virus, including EBV, from latency and thus favor the de novo infection and transformation of B lymphocytes.…”

Section: Commentsmentioning

confidence: 97%

Clinical usefulness of Epstein-Barr viral load in solid-organ transplantation

Buteau

Payá

2001

Liver Transpl

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Epstein‐Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid‐organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative‐PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of > 1,000 genome equivalents (GE)/0.5 μg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow‐up. In a minority of patients (3 of 32; 9.3%), ≥ 5,000 GE could be detected at least once during follow‐up. Reduction of immunosuppressive treatment decreased EBV DNA levels by ≥ 1 log10 unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

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“…96 In addition, the activation of the other herpesviruses human herpesvirus-6 and Epstein-Barr virus has been reported with CMV. [97][98][99] Cytomegalovirus is also suggested to be involved in liver rejection-including an association with chronic rejection. 100,101 CMV triggers inflammation in the graft by upregulation of cytokines, MHC antigens and adhesion molecules, and induces various chemokines and growth factors.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Infections After Orthotopic Liver Transplantation

Pedersen

Seetharam

2014

Journal of Clinical and Experimental Hepatology

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Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. ( J CLIN EXP HEPATOL 2014;4:347-360) I nfection after orthotopic liver transplantation (OLT) is a major cause of morbidity and mortality. Infection is estimated to occur in upto 80% of organ recipients. Bacterial infections are most frequent (70%), followed by viral (20%) and fungal infections (8%). 1,2,3 In addition to direct effects of infection and end-organ inflammation, pathogens may have a number of indirect effects that result in allograft injury, rejection and opportunistic superinfection.The risk of infection in liver transplant recipients is determined by the intensity of exposure to infectious agents and the overall level of immunosuppression. 4 In addition, conditions attendant to end-stage liver disease in the immediate perioperative period may render a recipient vulnerable to infection and include: neutropenia, deficits in mucocutaneous barrier integrity, presence of necrotic tissue, ischemia, diabetes mellitus, immunomodulating viruses, uremia, and protein-calorie malnutrition. 5 Infectious exposures come from many sources post liver transplant including: de novo (acquired acute) in the recipient, reactivation in the recipient, the donor organ, and nosocomial and time from transplant may provide clues to etiology (Figure 1). The overall level of immunosuppression is dependent upon the dose, duration, and choice of immunosuppression as well as underlying immune deficiencies. 6 Inflammatory responses to invading pathogens are often blunted by immunosuppressive therapy, and as a result, the classic signs or symptoms of infection may be absent. A high index of suspicion is need in the liver recipient, and a low threshold to perform invasive diagnostic procedures is often required. It is critical to identify clinical factors that predispose recipients to infection and much interest centers on identifying risk factors for infection after liver transplant. GENETIC POLYMORPHISMS IN THE INNATE IMMUNE SYSTEMIn addition to clinical factors that promote ...

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Posttransplant Lymphoproliferative Disease in Primary Epstein‐Barr Virus Infection after Liver Transplantation: The Role of Cytomegalovirus Disease

Cited by 236 publications

References 20 publications

Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient

Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient

Clinical usefulness of Epstein-Barr viral load in solid-organ transplantation

Infections After Orthotopic Liver Transplantation

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