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

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 PagliucaMajid Kazmi

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Abstract

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.
Original languageEnglish
Pages (from-to)1757-1763
Number of pages7
JournalClinical Infectious Diseases
Volume69
Issue number10
Early online date15 Jan 2019
DOIs
Publication statusPublished - 30 Oct 2019

Keywords

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

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