Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder

Abstract

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD.

Methods: We retrospectively studied 306 patients monitored for EBV DNAemia after Thymoglobulin-conditioned HCT to determine the utility of the monitoring in the management of PTLD. DNAemia was monitored weekly for ≥12 weeks post-transplantation.

Results: Reactivation was detected in 82% of patients. PTLD occurred in 14% of the total patients (17% of patients with reactivation). PTLD was treated with rituximab only when and if the diagnosis was established. This allowed us to evaluate potential DNAemia thresholds for pre-emptive therapy. We suggest 100,000-500,000 IU per mL whole blood as this would result in unnecessary rituximab administration to only 4-20% of patients and near zero mortality due to PTLD. After starting rituximab (for diagnosed PTLD), sustained regression of PTLD occurred in 25/25 (100%) patients in whom DNAemia became undetectable. PTLD progressed or relapsed in 12/17 (71%) patients in whom DNAemia was persistently detectable.

Discussion: In conclusion, for pre-emptive therapy of PTLD, we suggest threshold DNAemia of 100,000-500,000 IU/mL. Persistently detectable DNAemia after PTLD treatment with rituximab appears to have 71% positive predictive value and 100% negative predictive value for PTLD progression/relapse.

Keywords: Epstein-Barr virus infections; hematopoietic stem cell transplantation; herpesvirus 4; post-transplantation lymphoproliferative disorders; retrospective studies; rituximab; thymoglobulin.