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

Research output: Contribution to journalArticlepeer-review

Varun Mehra, Elijah Rhone, Stefani Widya, Mark Zuckerman, Victoria Potter, Kavita Raj, Austin Gladston Kulasekararaj, Donal P. McLornan, Hugues de Lavallade, Nana Benson-Quarm, Christina Lim, Sarah Ware, Malur Sudhanva, Omar Malik, Richard Nicholas, Paolo A. Muraro, Judith Marsh, Ghulam Jeelani Mufti, Eli Silber, Antonio Pagliuca & 1 more Majid Kazmi

Original languageEnglish
Pages (from-to)1757-1763
Number of pages7
JournalClinical Infectious Diseases
Issue number10
Early online date15 Jan 2019
Accepted/In press14 Jan 2019
E-pub ahead of print15 Jan 2019
Published30 Oct 2019


King's Authors


IntroductionAutologous 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.MethodsRetrospective 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.ResultsAll 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.ConclusionSymptomatic 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.

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