Clinical and genetic features of Epstein‐Barr virus‐triggered late‐onset primary hemophagocytic lymphohistiocytosis: Ten pedigrees study

Abstract

Dear Editor, In this study, we reported the clinical and genetic characteristics of 10 Epstein-Barr virus (EBV)-triggered late-onset primary hemophagocytic lymphohistiocytosis (HLH) patients. As HLH is a rare and devastating disorder characterized by uncontrolled immune activation resulting from the impaired function of natural killer and cytotoxic T cells.1 And HLH can be further classified as either primary or secondary based on the predisposing genetic deficiency.2–4 Although primary HLH usually arises in infants and children, the late-onset primary HLH is increasingly reported in the literature.5 It has been suggested that synergetic effects of the atypical heterozygous HLH-associated mutations and environmental triggers, including EBV infection, were associated with the pathogenesis of late-onset primary HLH.6 However, the role of EBV-infected cell subpopulation in primary HLH is unknown. Therefore, we retrospectively investigated 10 patients with EBV-triggered late-onset primary HLH (occurring at over 12 years of age) from June 2013 and June 2018 in our department. According to the Diagnostic Guidelines for HLH, all of the cases met at least five of eight criteria and thereby were diagnosed as HLH, and detailed clinical parameters are listed in Table 1. Pathological studies of bone marrow, lymph node, and pleural fluids samples demonstrated that abnormal T lymphocytes, which were characterized by CD2bri+CD4–CD5–CD7dim+CD8+CD45RA–CD45RO+ Ki67str+, existed in the bonemarrow of case 1 and 2. In contrast, abnormal NK cell phenotype, which was marked by CD7dim+CD8–CD11bdim/–CD16dim/+CD56dim/+/str+CD57–, existed in the bone marrow for cases 7, 9, 10, and pleural effusion of case 4. No malignant clone was found in any of these patients. Despite all the patients were treated with regimens based on HLH-2004 protocol and supportive therapy, seven of 10 patients died of disease progression