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Author Notes:

Correspondence: Shanmuganathan Chandrakasan, shanmuganathan.chandrakasan@emory.edu

O.S. was involved in the collection of the data, data analysis, and manuscript writing. D.K., J.S., and A.M. were involved in the collection of the data and analysis.

M.B., M.Q., S.Cho., L.L., H.E., M.H.W., and S.P. were involved in the clinical care and manuscript writing. S.C. was responsible for the project concept, design, analysis, manuscript writing, and project oversight.

The authors wish to acknowledge Drs. Suhag Parikh and Sampath Prahalad for their critical review of the manuscript and feedback.

Disclosures: S.C. serves on the advisory committee of SOBI. The other authors declare no competing interests.


Research Funding:

Oded Shamriz’s position was supported by the Raymond F. Schinazi International Exchange Program (SIEP), Emory University School of Medicine, Atlanta, GA 30322, USA.

his work was supported by NHLBI 1K08HL141635-01A1, Atlanta Pediatric Scholars Program K12 Scholar supported by grants K12HD072245 and U54AI082973 (to S.C.).

The Mills Foundation (to S.C) and the Henagan Foundation ( to S.C) Foundation (to S.C.).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • EBV
  • Hemophagocytic lymphohistiocytosis
  • HLH
  • Epstein-Barr virus
  • T cells
  • CD5 down regulation
  • Chronic active EBV
  • Lymphoproliferative diseases
  • Infection
  • Children
  • Immunodeficiency
  • Lymphocytes
  • Expansion
  • Diagnosis

T Cell-Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis (HLH) Occurs in Non-Asians and Is Associated with a T Cell Activation State that Is Comparable to Primary HLH

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Journal Title:

Journal of Clinical Immunology


Volume 41


, Pages 1582-1596

Type of Work:

Article | Final Publisher PDF


PURPOSE: T cell-Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (T cell-EBV-HLH) is prevalent in East Asia and has poor prognosis. Understanding of this disease is limited, and literature regarding prevalence in North America is scarce. Herein, we summarize our experience. METHODS: A retrospective analysis of T cell-EBV-HLH patients admitted to Children's Healthcare of Atlanta (GA, USA) from 2010 to 2020 was conducted. Additional immune studies were completed in a subset of patients. RESULTS: We report 15 patients (10 months-19 years of age) diagnosed with T cell-EBV-HLH. Nine patients were Hispanic, and the majority did not have primary HLH (p-HLH) gene defects. Soluble interleukin-2 receptor levels in T cell-EBV-HLH were significantly higher than other forms of secondary-HLH but comparable to p-HLH, and it correlated with disease severity at presentation. Natural killer cell function was decreased in most patients despite a negative workup for p-HLH. Depending on disease severity, initial therapy included dexamethasone or dexamethasone and etoposide. Refractory patients were managed with blended regimens that included one or more of the following therapies: combination chemotherapy, alemtuzumab, emapalumab, and nivolumab. Rituximab did not appreciably decrease EBV viremia in most patients. Non-critically ill patients responded well to immunosuppressive therapy and are long-term survivors without undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Alemtuzumab resulted in inflammation flare in two of the three patients. Three patients underwent allogeneic HSCT, with disease relapse noted in one. At a median follow-up of 3 years, 10 of the 15 patients are alive. CONCLUSION: T cell-EBV-HLH occurs in the USA among the non-Asian populations, especially in those who are Hispanic.

Copyright information:

© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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