Epstein - Barr Virus Infection of T and Natural Killer Cells Causes a Severe and Unusual Type of Hemophagocytic Lymphohistiocytosis among Hispanic Patients

עודד שמריז 1,2 Laura Lucas 1 Silvia T. Bunting 3 Michael Briones 1 Satheesh Chonat 1 Maa-Ohui Quarmyne 1 Shanmuganathan Chandrakasan 1
1Emory University School of Medicine, Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, USA
2Hadassah-Hebrew University Medical Center, Pediatric division, Jerusalem, Israel
3Pathology, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, USA

Introduction: Epstein-Barr virus (EBV) induced- hemophagocytic lymphohistiocytosis (HLH) is usually mediated through B cells. Herein, we describe our experience with a rare form of T and NK cell-mediated EBV-HLH.

Methods: A retrospective medical record analysis of children admitted with the diagnosis of T/NK cell-mediated EBV-HLH between 2010-2018 to the Children`s Healthcare of Atlanta medical center (GA, USA).

Results: The study included 10 patients (5 males, mean presenting age of 6.4 years; range: 1 to 19 years). Presentation consisted of fever, splenomegaly and coagulopathy in 9, 8 and 7 patients, respectively. Serum EBV DNA was identified in all the patients. In 5 patients, EBV was demonstrated in T or NK cells. NK cell activity was decreased or absent in 5 patients. High levels of soluble interleukin-2 receptor (≥2400 U/ml) were measured in 8 patients. CD3+CD8+CD5- T cell clone expansion was noted during workup. Treatment consisted of dexamethasone (n=10), etoposide (n=6) and cyclosporine A (n=3). Biological agents were given to 7 patients (rituximab (n=7), alemtuzumab (n=3) and anakinra (n=1). Intravenous immunoglobulins were given to 2 patients. Two patients underwent hematopoietic stem cell transplantation. Four out of 10 patients have died.

Conclusion: Early diagnosis and treatment of T/NK cell-mediated EBV-HLH is critical, as prognosis is often poor. CD5-CD8+ T cell expansion can be seen during immune workup of these patients.









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