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

• Authors: Oded Shamriz, Emory University; Deepak Kumar, Emory University; Jenny Shim, Emory University; Michael Briones, Emory University; Maa-Ohui Quarmyne, Emory University; Satheesh Chonat, Emory University; Laura Lucas, Childrens Healthcare of Atlanta; Holly Edington, Emory University; Michael White, Emory University; Advay Mahajan, Emory University; Sunita Park, Emory University; Shanmuganathan Chandrakasan, Emory University
• Journal Title: Journal of Clinical Immunology
• Volume: Volume 41
• Publisher: Springer Nature | 2021-06-26, Pages 1582-1596
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s10875-021-01073-9
• Subjects: Health Sciences, Immunology; Biology, Cell; Health Sciences, Oncology; Health Sciences, Pathology
• Keywords: 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

Abstract

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.