Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation In Autologous Hematopoietic Stem Cell Transplantation (HSCT) for Severe Multiple Sclerosis (MS).
Authors: Saccardi Riccardo , Fani Filippo , Repice Annamaria , Maggi Pietro , Gioia Massimo Di , Andreoli Elisabetta , Bosi Alberto , Guidi Stefano , Gozzini Antonella , Massacesi Luca , Amato Maria Pia , Nozzoli Chiara 
Published: October 2019

Abstract
Abstract 4537

INTRODUCTION.
Autologous HSCT is currently under investigation for the treatment of refractory, progressive MS. A better selection of patients and the use of less aggressive regimens resulted in a significant drop of Transplant-related Mortality (TRM), which is mostly related to immunosuppression. CMV and EBV tend to reactivate in ATG-treated allogeneic HSCT. We investigated the frequency of CMV/EBV viral load in a consecutive cohort of MS patients who underwent HSCT in our Center following BEAM and Anti-T Lymphocyte Globulin (ATG) conditioning regimen.

PATIENTS AND METHODS.
Thirty-one patients underwent auto-HSCT for severe MS in our Institution from 1999 to 2010. All patients were mobilized by Cyclophosphamide 4 g/sqm + G-CSF and conditioned with BEAM plus rabbit ATG (Thymoglobulin©) at a dose ranging between 7.5 and 10 mg/Kg. Monitoring of CMV/EBV DNA by quantitative PCR on either circulating Mononuclear Cells (MNC) or Whole Blood (WB) was performed in 29 pts. In 18 patients ≥2 tests were available for both CMV and EBV from +20 and +120 days. In 2006, following a case of severe CMV infection, a specific protocol was developed, aimed at monitoring on a weekly basis the viral load in case reactivation until complete negativisation. Pre-emptive treatment was administered in case of viral DNA load >1×103 copies/105MNC or >1×1044 copies/ml WB in two subsequent determinations.

RESULTS.
Overall 84 and 95 tests were carried out for CMV and EBV, respectively. 10/29 patients (34.5%) were shown positive for CMV at a median of 33,5 days from HSCT (28-47), whereas 11/29 patients (37.9%) were positive for EBV at a median of 29 days from HSCT (20-109). Five patients resulted positive for both viruses. According to the ongoing protocols, 20% of CMV+ patients and 18% of EBV+ patients received a pre-emptive treatment with a fast drop of viral load. In the other patients the reactivation was self-limiting in 2–3 weeks from the first positive determination. One patient developed a severe CMV infection at + 47 days successfully treated the iv administration of Gancyclovir and Foscarnet. One EBV+ patient developed fever which responded promptly after treatment with rituximab. Moreover, in 16/29 patients a sporadic assessment of CMV/EBV was performed at early (between +5 and + 20) and late phases (beyond 120 days) without any evidence of viral reactivation.

CONCLUSIONS.
Autologous HSCT with BEAM/ATG can be safely performed in MS patients. A significant reactivation of both CMV and EBV can occur in the 3 months following HSCT, possibly related to the ATG administration. Monitoring of viral load and, whenever necessary, pre-emptive anti-viral treatment should be performed in order to improve safety of HSCT in this subset of non-neoplastic patients.

Disclosures:
No relevant conflicts of interest to declare.