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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

1
Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.
2
Department of Neurology, King's College Hospital NHS Foundation Trust, Denmark Hill.
3
GKT School of Medical Education, Kings College London University.
4
Department of Virology, King's College Hospital NHS Foundation Trust, Denmark Hill.
5
Department of Hematology, Guy's and St. Thomas' NHS Foundation Trust.
6
Department of Neurology, Imperial College Healthcare, United Kingdom.
7
Department of Neuroimmunology, Imperial College London, United Kingdom.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

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

PMID:
30980715
DOI:
10.1093/cid/ciz047

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