Pre-hematopoietic stem cell transplant rituximab for Epstein-Barr Virus and post-transplant lymphoproliferative disorder prophylaxis in alemtuzumab recipients.

Overview

abstract

BACKGROUND: Epstein-Barr virus (EBV) reactivation and EBV-related post-transplant lymphoproliferative disorder (PTLD) are often fatal complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of EBV reactivation may be mitigated by depletion of B-cells with rituximab. Starting in January 2020, allo-HSCT recipients undergoing T-cell depletion with alemtuzumab received one dose of rituximab prior to transplant. OBJECTIVE: The objective of this study was to evaluate the cumulative incidence of EBV reactivation and EBV-PTLD in recipients of allo-HSCT and in-vivo T-cell depletion with alemtuzumab who received pre-HSCT rituximab compared to patients who did not. STUDY DESIGN: This was a single center retrospective analysis of adult patients who consecutively received an HLA-identical allo-HSCT between January 2019 and May 2021 and in-vivo T-cell depletion with alemtuzumab. Patients were included in the rituximab cohort if they received rituximab within 6 months prior to their transplant. The primary endpoint was incidence of EBV reactivation at day +180 amongst those receiving pre-HSCT rituximab versus those not receiving rituximab. Secondary endpoints included cumulative incidence of EBV-PTLD at 1 year, time to engraftment, immune reconstitution, and incidence of infections and acute graft-versus-host disease (aGVHD) at day +180. RESULTS: Eighty-six consecutive patients that received an allo-HSCT with alemtuzumab T-cell depletion were reviewed; 43 patients that received pre-HSCT rituximab after our protocol modification were compared to 43 patients who did not receive pre-HSCT rituximab prior to this change. Median age was 57 (IQR, 40-69) years and the majority of patients had acute myeloid leukemia or myelodysplastic syndrome. Baseline characteristics were similar between the cohorts. EBV reactivation at day +180 occurred in 23 (53%) patients without prior rituximab exposure versus 0 patients with pre-HSCT rituximab exposure (p<0.0001). Similarly, 6 patients without prior rituximab exposure developed PTLD at 1 year compared to no cases of PTLD among patients receiving pre-HSCT rituximab. There was no difference in neutrophil engraftment, incidence of infections, or aGVHD at day +180 between the two cohorts. There was a delay in time to platelet engraftment in the rituximab cohort [median 16 (IQR, 15-20) days vs 15 (IQR, 14-17) days, p=0.04)]. CONCLUSION: Administration of pre-HSCT rituximab prior to allo-HSCT in patients receiving T-cell depletion with alemtuzumab was associated with a significant decrease in the risk for EBV reactivation and EBV-PTLD, without increasing aGVHD or infection rates.