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

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

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  • Media type: E-Article
  • Title: Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis
  • Contributor: Mehra, Varun; Rhone, Elijah; Widya, Stefani; Zuckerman, Mark; Potter, Victoria; Raj, Kavita; Kulasekararaj, Austin; McLornan, Donal; de Lavallade, Hugues; Benson-Quarm, Nana; Lim, Christina; Ware, Sarah; Sudhanva, Malur; Malik, Omar; Nicholas, Richard; Muraro, Paolo A; Marsh, Judith; Mufti, Ghulam J; Silber, Eli; Pagliuca, Antonio; Kazmi, Majid A
  • imprint: Oxford University Press (OUP), 2019
  • Published in: Clinical Infectious Diseases
  • Language: English
  • DOI: 10.1093/cid/ciz047
  • ISSN: 1058-4838; 1537-6591
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Introduction</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &gt;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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>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.</jats:p> </jats:sec>
  • Access State: Open Access