Early Detection of Epstein-Barr Virus Related Disease.

Study Overview
=================
Brief Summary
-----------------
Epstein-Barr virus (EBV) is one of several herpesviruses that cause disease in humans. EBV virus has an oncogenic potential, and it has been associated with the development of a wide range of cancers. Previous studies have shown a close association between EBV and Post-Transplant Lymphoproliferative disorder (PTLD) in transplant recipients. As part of a preventive approach against PTLD, several transplantation units now monitor the occurrence of EBV-DNAemia after transplantation. However, there is little evidence to guide this strategy; nor is there consensus concerning either the best specimen to use for EBV analysis (whole blood or plasma). In this study investigators aim to optimise and validate a polymerase chain reaction (PCR)-test for EBV-DNA on, respectively, whole blood, plasma and a combination of plasma and lymphocytes. The investigators wish to determine which of the three tests best predicts current and future risk of development of EBV-related diseases such as mononucleosis and PTLD.

Detailed Description
-----------------
EBV is one of several herpesviruses that cause disease in humans. Primary EBV infection usually occurs in early childhood and is generally asymptomatic, while later infection may cause mononucleosis. As with other herpesviruses, primary infection is followed by persistent (lifelong) infection. EBV virus has an oncogenic potential, and it has been associated with the development of a wide range of cancers. Previous studies have shown a close association between EBV and PTLD in transplant recipients. As part of a preventive approach against PTLD, several transplantation units now monitor the occurrence of EBV-DNAemia after transplantation. However, there is little evidence to guide this strategy; nor is there consensus concerning either the best specimen to use for EBV analysis (whole blood or plasma) or the appropriate clinical action to take if EBV-DNAemia is detected. In this study investigators aim to optimise and validate a polymerase chain reaction (PCR)-test for EBV-DNA on, respectively, whole blood and a combination of plasma and lymphocytes. Results obtained with the two new methods will be compared with those from the already established World Health Organization (WHO) standardised EBV-PCR test on ethylenediaminetetraacetic acid (EDTA)-plasma. The result of all three tests will be evaluated relative to EBV-related symptoms and other diseases. The investigators wish to determine which of the three tests best predicts current and future risk of development of EBV-related diseases such as mononucleosis and PTLD.

Official Title
-----------------
Early Detection of Epstein-Barr Virus Related Disease. Improving Quantification of EBV in Blood Samples Using Polymerase Chain Reaction.

Conditions
-----------------
Mononucleosis, Post-transplant Lymphoproliferative Disorder, Epstein-Barr Virus Infections, Epstein-Barr Virus Related Malignancy, Epstein-Barr Viraemia, Epstein-Barr Virus-Related Hodgkin Lymphoma, Epstein-Barr Virus-Related Non-Hodgkin Lymphoma, Hemophagocytic Lymphohistiocytoses, Hemophagocytosis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients suspected for having EBV disease. Exclusion Criteria: If the patients has any contraindications for blood sampling.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Department of Kidney Medicine<br>Primarily transplant recipients undergoing monitoring for EBV and patients suspected for having PTLD. | |
| Department of Hematology<br>Patients diagnosed with PTLD and other kinds of lymphoma. Patients undergoing hematopoietic stem cell transplantation and patients with hemophagocytosis. | |
| Department of pediatrics<br>Children undergoing transplantation. Children diagnosed with hemophagocytic lymphohistiocytosis. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of proven EBV disease | Symptoms compatible with EBV disease combined with a tissue biopsy positive for EBV | From time of blood sampling up to 24 months. | 
| Incidence of probable EBV disease | Symptoms compatible with EBV disease combined with a positive EBV-PCR | From time of blood sampling up to 24 months. |