Features of Epstein-Barr Virus (EBV) reactivation after reduced intensity conditioning allogeneic hematopoietic stem cell transplantation

Abstract

This single centre study assessed the incidence, kinetics and predictive factors of Epstein-Barr Virus (EBV) reactivation and EBV-related lymphoproliferative diseases (LPDs) in 175 consecutive patients who received a reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT). The cumulative incidence of EBV reactivation at 6 months after allo-HSCT defined as an EBV PCR load above 1000 copies of EBV DNA/10 5 cells was 15%, and none of these patients experienced any sign or symptom of LPD. A total of 17 patients, who had EBV DNA levels exceeding 1000 copies/10 5 cells on two or more occasions, were pre-emptively treated with rituximab. With a median follow-up of 655 (range, 92-1542) days post allo-HSCT, there was no statistically significant difference in term of outcome between those patients who experienced an EBV reactivation and those who did not. In multivariate analysis, the use of antithymocyte globulin as part of the RIC regimen was the only independent risk factor associated with EBV reactivation (relative risk ¼ 4.9; 95% confidence interval, 1.1-21.0; P ¼ 0.03). We conclude that patients undergoing RIC allo-HSCT using anti-thymocyte globulin as part of the preparative regimen are at higher risk for EBV reactivation. However, this did not impact on outcome, as quantitative monitoring of EBV viral load by PCR and preemptive rituximab therapy allowed for significantly reducing the risk of EBV-related LPD.

A bit of antithymocyte globulin can take you a long way!

“…Indeed, the potential benefit of a 5 mg/kg total dose could be confirmed in other independent series from our group. 7,8 This is further supported by the findings from an ongoing study by the Acute Leukemia working party of EBMT, which did not show a deleterious impact on the survival of ATG in a homogeneous cohort of AML patients transplanted in first CR and given PBSC grafts from unrelated donors (Mohty et al, unpublished data). The use of higher doses of ATG (45 mg/kg total dose) and the more heterogeneous features of the study are likely to explain the negative results from the CIBMTR analysis.…”

B and T Lymphocyte Attenuator Mediates Inhibition of Tumor-Reactive CD8+ T Cells in Patients After Allogeneic Stem Cell Transplantation

“…In allo-SCT patients, PD-1 levels in the distinct subsets were evidently higher than those in corresponding healthy donor T cells. This is probably because of the presence of a long-lasting inflammatory milieu due to the pre-SCT conditioning regimen (29), development of alloreactive T cell responses (30), occurrence of graft-versus-host disease (GVHD), and reactivation of viruses and subsequent immune responses (31,32). The differential expression profiles of BTLA and PD-1 indicate that there is a distinct role for these molecules to exert their physiological function.…”

Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation

“…1,30 This is logical since the natural site of EBV tropism is B cells. After RIC these lymphocytes have a prolonged period to undergo virus-driven blast cell transformation in the absence of the nor-…”

“…29 RIC in combination with in vivo or ex vivo T-cell depletion has been shown to be a particularly important risk factor. 1,30 This is logical since the natural site of EBV tropism is B cells. After RIC these lymphocytes have a prolonged period to undergo virus-driven blast cell transformation in the absence of the nor-haematologica | 2014; 99(2) © F e r r a t a S t o r t i F o u n d a t i o n mally strictly regulated control from EBV-specific T cells.…”