Rituximab Prophylaxis of EBV Reactivation after Alternative Donor Transplants Following Anti-Thymocyte Globulin-Based Conditioning Regimens.

Background. Reactivation of Epstein Barr Virus (EBV) frequently occurs after allogeneic stem cell transplantation (ASCT) and EBV-induced lymphoproliferative disease is a potentially fatal complication.

Aim of the study. Prevent EBV reactivation and EBV-induced post-transplant lymphoproliferative disease (LPD) after ASCT from alternative donors following anti-thymocyte globulin (ATG)-based conditioning regimen.

Methods. In 2004, we initiated a pilot study with Rituximab given prophylactically on day +5 after an alternative donor transplant. We treated 68 patients with a fixed dose of 200 mg of Rituximab on day+5 and compared their outcome with a concurrent group of 77 controls who did not receive EBV prophylaxis. The two groups were comparable for patient and disease-associated variables, and all 145 patients received ATG as part of the conditioning regimen.

Results. Rituximab on day +5 was well tolerated without any serious adverse event. Patients receiving rituximab had a significantly lower rate of EBV reactivation 41% vs 78% (p=0.0001), a lower number of EBV copies at reactivation (3 vs 10, p=0.04), a lower viral load expressed as maximum number of EBV copies (79 vs 1321,p=0.001) and a significantly lower proportion of patients with EBV copies exceeding 1000 (10% vs 44% p=0.001). Time to neutrophil and platelet engraftment was not different between the 2 groups. In the group treated with Rituximab, there was a trend for a lower incidence of acute GvHD grade II-IV (21 vs 34%, p=0.07) and grade III-IV (2 vs 8%,p=0.07), and for a reduced transplant related mortality (28 vs 39% p=0.1). Actuarial survival at 1-year was better for the Rituximab group (67 vs 50% p=0.09), but this did reach statistical significance.

Conclusions. The use of Rituximab on day +5 after ASCT from alternative donors was safe and feasible. It did significantly lower the number of EBV copies at reactivation and the number of patients with an EBV load greater than 1000, at higher risk for EBV-related LPD. Thus, this approach may reduce the need of preemptive treatment or adoptive immunotherapy for EBV reactivation after an alternative donor transplant and may warrants further investigation.