Send to

Choose Destination
Clin Infect Dis. 2019 Jan 15. pii: ciz047. doi: 10.1093/cid/ciz047. [Epub ahead of print]

Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis.

Author information

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.
Department of Neurology, King's College Hospital NHS Foundation Trust, Denmark Hill.
GKT School of Medical Education, Kings College London University.
Department of Virology, King's College Hospital NHS Foundation Trust, Denmark Hill.
Department of Hematology, Guy's and St. Thomas' NHS Foundation Trust.
Department of Neurology, Imperial College Healthcare, United Kingdom.
Department of Neuroimmunology, Imperial College London, United Kingdom.



Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG.


Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records.


All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events.


Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.


Epstein-Barr virus infection; autologous hematopoietic stem cell transplantation; monoclonal gammopathy; multiple sclerosis; post-transplant lymphoproliferative disorder


Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center