title: Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: report of a nationwide survey from Korea Histiocytosis Working Party.
abstract: BACKGROUND
  We analyzed a nationwide registry of pediatric patients with hemophagocytic lymphohistiocytosis (HLH) in Korea to assess the clinical and genetic features and treatment outcomes in pediatric HLH.
  
  
  METHODS
  The Korea Histiocytosis Working Party retrospectively analyzed data on 251 pediatric patients diagnosed with HLH between 1996 and 2011.
  
  
  RESULTS
  In the study cohort, 25 cases were categorized with familial HLH, 64 with presumed secondary HLH, and 162 with unspecified HLH. Of 217 evaluable patients, 91 (42%) had concomitant Epstein-Barr virus infection. Of 238 evaluable patients, central nervous system (CNS) involvement, which was more frequent in the familial group, was evident in 81 cases (34%). Genetic tests revealed a predominant UNC13D mutation with a high incidence of two recurrent splicing mutations (c.118-308C>T and c.754-1G>C). The 5-yr overall survival rate was 68% (38% in the familial group and 81% in the presumed secondary group). The 5-yr overall survival rate among 32 patients who underwent allogeneic hematopoietic stem cell transplantation was 64%. In multivariate analysis, a younger age at diagnosis, severe transaminasemia, and a coagulation abnormality were independent prognostic factors for survival. Responses during initial treatments were also significant indicators of outcome.
  
  
  CONCLUSIONS
  Our study showed the unique predominance of a UNC13D mutation and vulnerability to Epstein-Barr virus infection in Korean children with HLH and emphasizes the prognostic significance of age, liver dysfunction, and treatment responses in this disease. A multicenter prospective trial that builds on the present results is warranted to identify subgroups of patients with a poor prognosis and identify optimal treatments.
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Kyung-Nam
authors.initials: KN
authors.lastname: Koh
authors.forename: Ho Joon
authors.initials: HJ
authors.lastname: Im
authors.forename: Nak-Gyun
authors.initials: NG
authors.lastname: Chung
authors.forename: Bin
authors.initials: B
authors.lastname: Cho
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Chuhl Joo
authors.initials: CJ
authors.lastname: Lyu
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hee Jo
authors.initials: HJ
authors.lastname: Baek
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.forename: Hoi Soo
authors.initials: HS
authors.lastname: Yoon
authors.forename: Young Tak
authors.initials: YT
authors.lastname: Lim
authors.forename: Heung Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Kyung Ha
authors.initials: KH
authors.lastname: Ryu
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Seo
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D008297:Male; D009154:Mutation; D063868:Patient Outcome Assessment; D011379:Prognosis; D062486:Public Health Surveillance; D012042:Registries; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
keywords: allogeneic hematopoietic stem cell transplantation; genetic mutation; hemophagocytic lymphohistiocytosis; prognostic factors; survival