Introduction: Epstein-Barr virus (EBV) is strongly associated with 50-80% of cases of post-transplant lymphoproliferative disorders (PTLD). Transplant centers often measure peripheral blood viral loads via nucleic acid testing (NAT), both pre-PTLD to inform preemptive interventions, or post-PTLD to assess treatment responses. To our knowledge the change in EBV load within the same patient post-PTLD has not been assessed as a prognostic marker.
Methods: As part of our ongoing NIH-funded PTLD MSMS study of metagenomic sequencing for microbial DNA from PTLD tissues or plasma, we have collected more than 400 such samples from 3 large USA centers, along with detailed clinical data. In this study we focus on the peripheral blood EBV NAT results by PCR after EBV tumor positive PTLD development. To account for differences in sample source and units between centers, we calculated the difference in load within the same patient, by selecting the value closest after PTLD diagnosis and the value furthest out after PTLD diagnosis. We analyzed the associations of this change in EBV load post-PTLD to 5-year event-free survival (events defined as patient death, allograft loss or repeat PTLD event).
Results: We have data so far on 432 EBV peripheral blood NAT results, from 164 unique PTLD patients, of which 177 results are pre-PTLD and 255 are post-PTLD (median 2.5 loads/patient, range 1-8). When restricting to those PTLD tumors being positive for EBV expression, we had 50 patients with at least 2 post-PTLD evaluable EBV NAT values. A decrease in EBV load was seen in 37 patients (range 7-100%, median time 238 days between values), while 7 patients had all negative values post-PTLD (median time 169 days between values). Another 6 patients had an increase in EBV loads (range 1.6 to 193%, median time 131 days between values). The 5-year event-free Kaplan-Meier survival curves were worst in those with an increase in EBV load post-PTLD, best in those with negative EBV loads and intermediate in those with a decrease in load (p = 0.058; Figure).

Conclusions: A negative or reduced post-PTLD EBV load, within the same patient, associates to a better prognosis than an increase in EBV load.