Risk factors for EBV reactivation and impact of graft composition following GVHD prophylaxis with rabbit ATG or PTCy.

BACKGROUND

EBV reactivation is frequent after allogeneic HCT and can lead to post-transplant lymphoproliferative disorder (PTLD). While ATG and PTCy are established strategies to prevent GVHD, their comparative impact on EBV reactivation remains insufficiently characterized.

METHODS

We conducted a retrospective study in patients who received either rabbit ATG or PTCy. Primary endpoints were incidences of positive and high-level EBV DNAemia (≥10⁴ copies/mL). Secondary endpoints were incidence of PTLD, predictive risk factors for EBV reactivation, GVHD, survival, immune reconstitution and response to hepatitis B vaccination.

RESULTS

286 patients were included; 215 received ATG and 71 PTCy. High-level EBV DNAemia occurred earlier and more frequently after ATG (42.3% vs 22.5%, p < 0.0001). All PTLDs were in ATG recipients. In these, high CD19+ B cell doses ( ≥ 3.88 × 107/kg) and elevated CD19+/CD8+ ratio in grafts were independently associated with high EBV DNAemia, a relationship not observed with PTCy. ATG-treated patients exhibited delayed T-cell reconstitution, and rituximab was associated with sustained B-cell depletion and impaired hepatitis B immunity with no impact on survival.

CONCLUSION

Rabbit ATG, high CD19+ content and CD19+/CD8+ ratio in infused grafts are associated with a higher risk of EBV. Novel strategies targeting these patients while preserving immune reconstitution are warranted.