Background. Patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT) are endangered by
developing Epstein-Barr virus-related post-transplant lymfoprolipherative disease (EBV-LPD). The aims of the study
were to retrospectively characterise the viral loads in four patients who died of this complication, and to test possible
risk factors for EBV reactivation in a prospectively observed cohort of children after AHSCT.
Methods and Results. Serial DNA samples extracted from whole blood from four patients who died of post-transplant
EBV-LPD in year 2000 were retrospectively analysed for EBV load using quantitative real-time PCR. First
detection of EBV activation preceded death by 24-91 days. All four patients exceeded a viral load of one million EBV
copies per 100,000 human genome equivalents. A cohort of 72 children undergoing AHSCT between 2001-2004 was
prospectively followed-on using the same quantification method from regularly obtained samples of whole blood, and
clinical and laboratory data were recorded on a weekly basis, totalling at 3,896 person-weeks of observation. Approximately
one half of the cohort experienced at least one episode of EBV reactivation during the first 100 days after
AHSCT, four of the episodes being accompanied with viral loads higher than our provisional threshold of 10,000
copies per 100,000 human genome equivalents. Three of the four patients developed EBV-LPD and were successfully
treated by intravenous administration of anti-CD20 antibody. Testing of possible clinical and laboratory predictors
of EBV reactivation did not reveal any clinically useful association.
Conclusions. The cornerstone of predicting EBV-LPD in AHSCT is a regular monitoring of EBV viral load using
quantitative methods. Using this strategy with a threshold of 10,000 EBV copies per 100,000 human genome equivalents
was proved to be effective, as shown by no death of EBV for the study period, compared to four cases in the
year before the quantitative monitoring.
EBV, lymphoproliferative disease, allogeneic haematopoietic stem cell transplantation, PCR.