Four individuals had main HLH, 48 individuals had secondary HLH (20 infection-associated, 18 neoplasm-associated, and 10 autoimmune-associated HLH), and eight individuals had HLH of unknown cause. The 5-yr GS-9973 (Entospletinib) overall survival (OS) rate for those HLH individuals was 59.9%. The 5-yr OS rates for individuals with main, infection-associated, neoplasm-associated, autoimmune-associated, and unfamiliar cause HLH were 25.0%, 85.0%, 26.7%, 87.5%, and 62.5%, respectively. Using multivariate analysis, neoplasm-induced HLH (variants [13]. Moreover, secondary HLH induced by Epstein-Barr disease (EBV) infection experienced a relatively high incidence, and the 5-yr overall survival (OS) rate was 68% in 251 Korean children with HLH [13]. According GS-9973 (Entospletinib) to the reports on HLH in adults, neoplasms as causes are more common in adults than in children [16]. Additionally, secondary HLH is the most common HLH subtype in adults [17]. However, to date, there have been no data concerning HLH in adult individuals or a comparison of HLH in pediatric and adult individuals in Korea. Consequently, we targeted to retrospectively investigate the causes and characteristics of HLH in both pediatric and adult individuals with different HLH subtypes with this study. We also investigated the survival rates of and risk factors for poor prognosis in children and adults with HLH. Materials and GS-9973 (Entospletinib) methods 1. Subjects and honest statement With this study, individuals diagnosed with HLH at Keimyung University or college Dongsan Hospital and Yeungnam University or college Medical Center in Daegu, Korea between January 2001 and December 2019 were investigated. The medical records of individuals with HLH were retrospectively examined for age at analysis, sex, HLH etiology, treatment regimen, and death. 2. Definition and methods HLH was diagnosed according to the diagnostic criteria presented from the Histiocyte Society in 1991 and updated in 2004 [8,11]. According to the HLH-2004 guideline, at least five of GS-9973 (Entospletinib) the eight outlined items must be met for the analysis of HLH: (1) fever 38.5C; (2) splenomegaly; (3) bicytopenia influencing 2 cell lines (hemoglobin 90 g/L [hemoglobin 100 g/L in babies 4 weeks], platelet 100109/L, and neutrophil 1.0109/L); (4) hyperferritinemia (ferritin 500 g/L); (5) hypertriglyceridemia (fasting triglyceride 3.0 mmol/L [265 mg/dL]) and/or hyperfibrinogenemia (fibrinogen, 1.5 g/L); (6) hemophagocytosis in the bone marrow (BM), lymph node, spleen, or liver without evidence of malignancy; (7) elevated levels of soluble CD25 (also called interleukin-2 receptor) 2,400 U/mL; and (8) GS-9973 (Entospletinib) low or absent natural killer (NK) cell activity [5,11]. In this study, NK cell activity could not be tested using circulation cytometry; instead, interferon- was measured by enzyme-linked immunosorbent assay using the NK Vue kit (ATgen, Seongnam, Korea) through Seoul Clinical Laboratories (Yongin, Korea; http://www.scllab.co.kr) [18]. Since this external test method was not performed daily, the results of this test were available after several days. Therefore, it was not used directly like a diagnostic criterion but was referenced in previously diagnosed HLH individuals. Additionally, mutations in the genes of standard FHL (pairwise assessment. The 95% confidence intervals (CIs) were estimated using the means and standard errors. The Cox proportional risks model was utilized for multivariate analysis. The (urinary tract illness)2???Adenovirus1???(meningitis)1???variants, much like previous Korean data [13]. Interestingly, one patient with FHL type 2 (variant) with this study was a 28.3-year-old man. In the beginning, this patient was diagnosed with T-cell lymphoma that progressed aggressively, and he met the criteria of HLH with multiple organ failure. Because of this amazing disease course, the physician performed a genetic test and he MHS3 was eventually diagnosed with adult FHL. Although main HLH is commonly diagnosed in children, several examples of genetically confirmed HLH in adults have recently been reported [21-23]. Allogenic stem cell transplantation is definitely a recommended therapy for adult main HLH [23]. Furthermore, a 9.2-year-old pediatric individual with XLP1 (variant) was initially diagnosed with EBV-associated lymphoproliferative disease, which also proven very aggressive features of HLH with multiple organ failure. As there was no pathogenic variant based on the conventional genetic checks for and em UNC13D /em , the pediatrician.