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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1165-1171
PLENARY PAPER
Frequent monitoring of Epstein-Barr virus DNA load in
unfractionated whole blood is essential for early detection of
posttransplant lymphoproliferative disease in high-risk
patients
Servi J. C. Stevens,
Erik
A. M. Verschuuren,
Inge Pronk,
Wim van der Bij,
Martin C. Harmsen,
T. Hauw The,
Chris J. L. M. Meijer,
Adriaan J. C. van den
Brule, and
Jaap M. Middeldorp
From the Department of Pathology, University
Hospital Vrije Universiteit, Amsterdam, The Netherlands, and the
Departments of Clinical Immunology and Pulmonary Diseases, University
Hospital Groningen, Groningen, The Netherlands.
Posttransplant lymphoproliferative disease (PTLD) is a frequent and
severe Epstein-Barr virus (EBV)-associated complication in
transplantation recipients that is caused by iatrogenic suppression of
T-cell function. The diagnostic value of weekly EBV DNA load monitoring was investigated in prospectively collected unfractionated whole blood and serum samples of lung transplantation (LTx) recipients with and without PTLD. In PTLD patients, 78% of tested whole blood samples were above the cut-off value of quantitative
competitive polymerase chain reaction (Q-PCR) (greater than
2000 EBV DNA copies per mL blood), with the majority of patients having
high viral loads before and at PTLD diagnosis. Especially in a primary
EBV-infected patient and in patients with conversion of
immunosuppressive treatment, rapid increases in peripheral blood EBV
DNA load diagnosed and predicted PTLD. In non-PTLD transplantation
recipients, only 3.4% of the whole blood samples was above the cut-off
value (P < .0001) despite heavy immune suppression and
cytomegalovirus (CMV)-related disease. These findings illustrate the
clinical importance of frequent EBV DNA load monitoring in LTx
recipients. The increased EBV DNA loads in PTLD patients were
restricted to the cellular blood compartment, as parallel serum samples
were all below cut-off value, which indicates absence of lytic viral
replication. EBV+ cells in PTLD patients have a very short
doubling time, which can be as low as 56 hours, thereby creating the
need for high screening frequency in high-risk patients. Furthermore,
it is shown that EBV and CMV can reactivate independently in LTx
recipients and that EBV DNA load monitoring may be useful in
discriminating PTLD from rejection.

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