Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea: Report of a nationwide survey from Korea Histiocytosis Working Party

On behalf of the Korea Histiocytosis Working Party

Research output: Contribution to journalArticle

25 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalEuropean Journal of Haematology
Volume94
Issue number1
DOIs
StatePublished - 1 Jan 2015

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Histiocytosis
Hemophagocytic Lymphohistiocytosis
Korea
Pediatrics
Epstein-Barr Virus Infections
Mutation
Survival Rate
Hematopoietic Stem Cell Transplantation
Surveys and Questionnaires
Multicenter Studies
Registries
Liver Diseases
Cohort Studies
Therapeutics
Multivariate Analysis
Central Nervous System
Survival
Incidence

Keywords

  • Allogeneic hematopoietic stem cell transplantation
  • Genetic mutation
  • Hemophagocytic lymphohistiocytosis
  • Prognostic factors
  • Survival

Cite this

@article{2898825ddc334a81aeed26d0e080bfe5,
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. Conclusion: 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.",
keywords = "Allogeneic hematopoietic stem cell transplantation, Genetic mutation, Hemophagocytic lymphohistiocytosis, Prognostic factors, Survival",
author = "{On behalf of the Korea Histiocytosis Working Party} and Koh, {Kyung Nam} and Im, {Ho Joon} and Chung, {Nak Gyun} and Bin Cho and Kang, {Hyoung Jin} and Kang, {Hyoung Jin} and Shin, {Hee Young} and Yoo, {Keon Hee} and Koo, {Hong Hoe} and Kim, {Hee Jin} and Baek, {Hee Jo} and Hoon Kook and Yoon, {Hoi Soo} and Lim, {Young Tak} and Kim, {Heung Sik} and Ryu, {Kyung Ha} and Seo, {Jong Jin}",
year = "2015",
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Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea : Report of a nationwide survey from Korea Histiocytosis Working Party. / On behalf of the Korea Histiocytosis Working Party.

In: European Journal of Haematology, Vol. 94, No. 1, 01.01.2015, p. 51-59.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinical features, genetics, and outcome of pediatric patients with hemophagocytic lymphohistiocytosis in Korea

T2 - Report of a nationwide survey from Korea Histiocytosis Working Party

AU - On behalf of the Korea Histiocytosis Working Party

AU - Koh, Kyung Nam

AU - Im, Ho Joon

AU - Chung, Nak Gyun

AU - Cho, Bin

AU - Kang, Hyoung Jin

AU - Kang, Hyoung Jin

AU - Shin, Hee Young

AU - Yoo, Keon Hee

AU - Koo, Hong Hoe

AU - Kim, Hee Jin

AU - Baek, Hee Jo

AU - Kook, Hoon

AU - Yoon, Hoi Soo

AU - Lim, Young Tak

AU - Kim, Heung Sik

AU - Ryu, Kyung Ha

AU - Seo, Jong Jin

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

KW - Allogeneic hematopoietic stem cell transplantation

KW - Genetic mutation

KW - Hemophagocytic lymphohistiocytosis

KW - Prognostic factors

KW - Survival

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