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


Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
30 10 2019
Historique:
received: 28 10 2018
accepted: 14 01 2019
pubmed: 14 4 2019
medline: 26 9 2020
entrez: 14 4 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30980715
pii: 5455218
doi: 10.1093/cid/ciz047
doi:

Substances chimiques

Antilymphocyte Serum 0
DNA, Viral 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1757-1763

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Auteurs

Varun Mehra (V)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Elijah Rhone (E)

Department of Neurology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Stefani Widya (S)

GKT School of Medical Education, Kings College London University.

Mark Zuckerman (M)

Department of Virology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Victoria Potter (V)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Kavita Raj (K)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.
Department of Hematology, Guy's and St. Thomas' NHS Foundation Trust.

Austin Kulasekararaj (A)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Donal McLornan (D)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.
Department of Hematology, Guy's and St. Thomas' NHS Foundation Trust.

Hugues de Lavallade (H)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Nana Benson-Quarm (N)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Christina Lim (C)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Sarah Ware (S)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Malur Sudhanva (M)

Department of Virology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Omar Malik (O)

Department of Neurology, Imperial College Healthcare, United Kingdom.

Richard Nicholas (R)

Department of Neurology, Imperial College Healthcare, United Kingdom.

Paolo A Muraro (PA)

Department of Neurology, Imperial College Healthcare, United Kingdom.
Department of Neuroimmunology, Imperial College London, United Kingdom.

Judith Marsh (J)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Ghulam J Mufti (GJ)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Eli Silber (E)

Department of Neurology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Antonio Pagliuca (A)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.

Majid A Kazmi (MA)

Department of Hematology, King's College Hospital NHS Foundation Trust, Denmark Hill.
Department of Hematology, Guy's and St. Thomas' NHS Foundation Trust.

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Classifications MeSH