Incidence of Epstein-Barr Virus (EBV) Detection in the Blood, Pre-Emptive Therapy, and EBV-Posttransplantation Lymphoproliferative Disorder (EBV-PTLD) after Allogeneic Hematopoietic Cell Transplantation (HCT) across a Broad Range of HCT Approaches and All Graft Sources

Latent EBV infection can lead to EBV-PTLD when proliferating, EBV+ B cells are insufficiently controlled by cellular immunity. At the National Institutes of Health (NIH), all HCT recipients are monitored weekly from day 0-100 with whole blood EBV qPCR. We evaluated the cumulative incidence (CI) of EBV-related events across 4 T-cell manipulation strategies (posttransplantation cyclophosphamide (PTCy), proximal serotherapy, ex vivo T cell depletion (TCD), and calcineurin/mTOR inhibitor (CNI/mTORi)-based), across all graft sources (marrow (BM), peripheral blood (PBSC), and umbilical cord blood (UCB)), and across regimens with and without mTORi drugs. The CI of EBV events (detection of any EBV in blood (Any-EBV), detection of EBV > 3 log10 IU/mL (>3-EBV), pre-emptive therapy for EBV (EBV-Tx), and EBV-PTLD) were determined, with death as a competing risk. EBV-tx included rituximab and/or EBV-specific T-cells. Any-EBV and >3-EBV events were captured through day +100 and EBV-Tx and EBV-PTLD events were captured through 1-year post-HCT. Included are 356 consecutive patients receiving 1st HCT at NIH from 2011-2017 with sufficient weekly day 0-100 EBV qPCRs (> 63% of specimens) and 1 year of follow-up of survivors. Fig 1 shows cohort characteristics. Among T-cell manipulation strategies, the CI of Any-EBV and >3-EBV was lowest for serotherapy, p=0.0007 and p=0.0006, with no difference among strategies in the CI of EBV-Tx or EBV-PTLD. By graft source, UCB had the highest CI of Any-EBV at day +100, p=0.001, with no difference in the CI of >3-EBV owing to higher CI of EBV-Tx among UCB recipients compared to BM and PBSC grafts, p 3-EBV, but no difference in the CI of EBV-Tx or EBV-PTLD. Within CNI/mTORi-based approaches, the CI of Any-EBV and >3-EBV was lower for CNI+mTORi vs CNI without mTORi, p=0.004 and p=0.002, and the CI of EBV-Tx was 3% for CNI+mTORi vs 14% for CNI without mTORi, p=0.009, with no difference in the CI of EBV-PTLD. Among PTCy-containing approaches, with or without serotherapy, there were no differences in the CI of Any-EBV, >3-EBV, EBV-Tx, or EBV-PTLD. The CI of EBV events are summarized in Fig 2. While EBV detection in blood was common post-HCT, the clinical significance of detection and the role of pre-emptive therapy seem to vary by T-cell manipulation strategy, graft source, and use of mTORi. The finding of less EBV detection with mTORi-containing regimens across approaches warrants further investigation into the clinical significance and underlying mechanisms.