Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

Abstract

SUMMARYEpstein-Barr virus (EBV) DNA measurement is being incorporated into routine medical practice to help diagnose, monitor, and predict posttransplant lymphoproliferative disorder (PTLD) in immunocompromised graft recipients. PTLD is an aggressive neoplasm that almost always harbors EBV DNA within the neoplastic lymphocytes, and it is often fatal if not recognized and treated promptly. Validated protocols, commercial reagents, and automated instruments facilitate implementation of EBV load assays by real-time PCR. When applied to either whole blood or plasma, EBV DNA levels reflect clinical status with respect to EBV-related neoplasia. While many healthy transplant recipients have low viral loads, high EBV loads are strongly associated with current or impending PTLD. Complementary laboratory assays as well as histopathologic examination of lesional tissue help in interpreting modest elevations in viral load. Circulating EBV levels in serial samples reflect changes in tumor burden and represent an effective, noninvasive tool for monitoring the efficacy of therapy. In high-risk patients, serial testing permits early clinical intervention to prevent progression toward frank PTLD. Restoring T cell immunity against EBV is a major strategy for overcoming PTLD, and novel EBV-directed therapies are being explored to thwart virus-driven neoplasia.

Epstein-Barr Virus DNAemia in Iranian Liver Transplant Recipients and Assessment of Its Variation in Posttransplant Lymphproliferative Disorder Patients by Quantitative Polymerase Chain Reaction Assay

“…The data showed that the median of maximum viral loads were significantly higher in the PTLD patients (4035 copies/mL) than nonaffected patients (500 copies/mL), consistent with several previous studies. [3][4][5] As we detected in this study, a wide range of EBV loads were observed in liver transplant patients. This was because of involvement of multiple host factors such as age of transplant, active primary infection, different underlying disease, immunosuppressive drug regimen, and intensity.…”

“…31,35 As shown in several studies, the incidence of PTLD is higher in pediatric than adult liver transplant patients. [1][2][3] The Scientific Registry of Transplant Recipients (SRTR) reported that 82% PTLDs occur in children aged < 17 years. 36 In the current study, more than 88% (30 of 34 patients) of PTLD cases occurred in children aged < 12 years.…”

“…This ubiquitous virus 90% adults worldwide. [3][4][5] It is associated with different malignancies and disorders such as Hodgkin lymphoma, non-Hodgkin lymphoma, Burkitt lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and posttransplant lympho proliferative disorders (PTLDs). 6,7 In immunocompetent individuals, EBV causes infectious mononucleosis, an acute but self-limited disease that affects children and young adults.…”

“…It is classified histologically into 4 groups: (1) early lesions, (2) polymorphic PTLD, (3) monomorphic PTLD, and (4) classic Hodgkin-lymphoma-type PTLD. 3 Based on clinical and histologic features, the diagnosis of PTLD and its differentiation from organ rejection often are difficult, and use of a sensitive test such as real-time polymerase chain reaction (PCR) is recommended. [13][14][15] The high EBV viral load in the plasma and/or peripheral blood mononuclear cells can serve as a reliable marker for development of PTLD.…”

Post-transplant lymphoproliferative disorder presenting with skin ulceration in a renal transplant recipient who achieved sustained remission with rituximab therapy: A case report

“…Quantification of the plasma EBV-DNA level may facilitate the monitoring of treatment response and it has been found to be effective in different types of lymphoproliferative diseases (13)(14)(15). For cases responding to treatment, circulating EBV-DNA falls to undetectable levels when complete remission is achieved (13).…”