Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study

Autores
Bergsten, Elisabet; Horne, AnnaCarin; Hed Myrberg, Ida; Aricó, Maurizio; Astigarraga, Itziar; Ishii, Eiichi; Janka, Gritta; Ladisch, Stephan; Lehmberg, Kai; McClain, Kenneth L.; Minkov, Milen; Nanduri, Vasanta; Rosso, Diego; Sieni, Elena; Winiarski, Jacek; Henter, Jan Inge
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged ,18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P 5 .035). For children with verified FHL (family history/genetically verified, n 5 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n 5 53) was significantly lower (52%; 95% CI, 38-65) (P 5 .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival.
Fil: Bergsten, Elisabet. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Horne, AnnaCarin. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Hed Myrberg, Ida. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Aricó, Maurizio. Children Hospital Giovanni XXIII; Italia
Fil: Astigarraga, Itziar. Universidad del País Vasco; España
Fil: Ishii, Eiichi. Ehime University; Japón
Fil: Janka, Gritta. Universitat Hamburg; Alemania
Fil: Ladisch, Stephan. Children’s National Medical Center; Estados Unidos
Fil: Lehmberg, Kai. Universitat Hamburg; Alemania
Fil: McClain, Kenneth L.. Baylor College of Medicine; Estados Unidos
Fil: Minkov, Milen. Universidad de Viena; Austria
Fil: Nanduri, Vasanta. Watford General Hospital; Reino Unido
Fil: Rosso, Diego. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sieni, Elena. Universitaria A. Meyer Children Hospital; Italia
Fil: Winiarski, Jacek. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Materia
HLH
Children
Stem Cell Transplantation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/156554

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oai_identifier_str oai:ri.conicet.gov.ar:11336/156554
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 studyBergsten, ElisabetHorne, AnnaCarinHed Myrberg, IdaAricó, MaurizioAstigarraga, ItziarIshii, EiichiJanka, GrittaLadisch, StephanLehmberg, KaiMcClain, Kenneth L.Minkov, MilenNanduri, VasantaRosso, DiegoSieni, ElenaWiniarski, JacekHenter, Jan IngeHLHChildrenStem Cell Transplantationhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged ,18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P 5 .035). For children with verified FHL (family history/genetically verified, n 5 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n 5 53) was significantly lower (52%; 95% CI, 38-65) (P 5 .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival.Fil: Bergsten, Elisabet. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Horne, AnnaCarin. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Hed Myrberg, Ida. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Aricó, Maurizio. Children Hospital Giovanni XXIII; ItaliaFil: Astigarraga, Itziar. Universidad del País Vasco; EspañaFil: Ishii, Eiichi. Ehime University; JapónFil: Janka, Gritta. Universitat Hamburg; AlemaniaFil: Ladisch, Stephan. Children’s National Medical Center; Estados UnidosFil: Lehmberg, Kai. Universitat Hamburg; AlemaniaFil: McClain, Kenneth L.. Baylor College of Medicine; Estados UnidosFil: Minkov, Milen. Universidad de Viena; AustriaFil: Nanduri, Vasanta. Watford General Hospital; Reino UnidoFil: Rosso, Diego. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sieni, Elena. Universitaria A. Meyer Children Hospital; ItaliaFil: Winiarski, Jacek. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaAmerican Society of Hematology2020-08-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/156554Bergsten, Elisabet; Horne, AnnaCarin; Hed Myrberg, Ida; Aricó, Maurizio; Astigarraga, Itziar; et al.; Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study; American Society of Hematology; Blood Advances; 4; 15; 11-8-2020; 3754-37662473-95372473-9529CONICET DigitalCONICETenginfo:eu-repo/semantics/reference/url/http://hdl.handle.net/11336/41228info:eu-repo/semantics/altIdentifier/doi/10.1182/bloodadvances.2020002101info:eu-repo/semantics/altIdentifier/url/https://ashpublications.org/bloodadvances/article/4/15/3754/461773/Stem-cell-transplantation-for-children-withinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:40:56Zoai:ri.conicet.gov.ar:11336/156554instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:40:56.838CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
title Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
spellingShingle Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
Bergsten, Elisabet
HLH
Children
Stem Cell Transplantation
title_short Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
title_full Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
title_fullStr Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
title_full_unstemmed Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
title_sort Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
dc.creator.none.fl_str_mv Bergsten, Elisabet
Horne, AnnaCarin
Hed Myrberg, Ida
Aricó, Maurizio
Astigarraga, Itziar
Ishii, Eiichi
Janka, Gritta
Ladisch, Stephan
Lehmberg, Kai
McClain, Kenneth L.
Minkov, Milen
Nanduri, Vasanta
Rosso, Diego
Sieni, Elena
Winiarski, Jacek
Henter, Jan Inge
author Bergsten, Elisabet
author_facet Bergsten, Elisabet
Horne, AnnaCarin
Hed Myrberg, Ida
Aricó, Maurizio
Astigarraga, Itziar
Ishii, Eiichi
Janka, Gritta
Ladisch, Stephan
Lehmberg, Kai
McClain, Kenneth L.
Minkov, Milen
Nanduri, Vasanta
Rosso, Diego
Sieni, Elena
Winiarski, Jacek
Henter, Jan Inge
author_role author
author2 Horne, AnnaCarin
Hed Myrberg, Ida
Aricó, Maurizio
Astigarraga, Itziar
Ishii, Eiichi
Janka, Gritta
Ladisch, Stephan
Lehmberg, Kai
McClain, Kenneth L.
Minkov, Milen
Nanduri, Vasanta
Rosso, Diego
Sieni, Elena
Winiarski, Jacek
Henter, Jan Inge
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HLH
Children
Stem Cell Transplantation
topic HLH
Children
Stem Cell Transplantation
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged ,18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P 5 .035). For children with verified FHL (family history/genetically verified, n 5 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n 5 53) was significantly lower (52%; 95% CI, 38-65) (P 5 .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival.
Fil: Bergsten, Elisabet. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Horne, AnnaCarin. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Hed Myrberg, Ida. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Aricó, Maurizio. Children Hospital Giovanni XXIII; Italia
Fil: Astigarraga, Itziar. Universidad del País Vasco; España
Fil: Ishii, Eiichi. Ehime University; Japón
Fil: Janka, Gritta. Universitat Hamburg; Alemania
Fil: Ladisch, Stephan. Children’s National Medical Center; Estados Unidos
Fil: Lehmberg, Kai. Universitat Hamburg; Alemania
Fil: McClain, Kenneth L.. Baylor College of Medicine; Estados Unidos
Fil: Minkov, Milen. Universidad de Viena; Austria
Fil: Nanduri, Vasanta. Watford General Hospital; Reino Unido
Fil: Rosso, Diego. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sieni, Elena. Universitaria A. Meyer Children Hospital; Italia
Fil: Winiarski, Jacek. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
Fil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia
description We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged ,18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P 5 .035). For children with verified FHL (family history/genetically verified, n 5 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n 5 53) was significantly lower (52%; 95% CI, 38-65) (P 5 .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival.
publishDate 2020
dc.date.none.fl_str_mv 2020-08-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/156554
Bergsten, Elisabet; Horne, AnnaCarin; Hed Myrberg, Ida; Aricó, Maurizio; Astigarraga, Itziar; et al.; Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study; American Society of Hematology; Blood Advances; 4; 15; 11-8-2020; 3754-3766
2473-9537
2473-9529
CONICET Digital
CONICET
url http://hdl.handle.net/11336/156554
identifier_str_mv Bergsten, Elisabet; Horne, AnnaCarin; Hed Myrberg, Ida; Aricó, Maurizio; Astigarraga, Itziar; et al.; Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study; American Society of Hematology; Blood Advances; 4; 15; 11-8-2020; 3754-3766
2473-9537
2473-9529
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/reference/url/http://hdl.handle.net/11336/41228
info:eu-repo/semantics/altIdentifier/doi/10.1182/bloodadvances.2020002101
info:eu-repo/semantics/altIdentifier/url/https://ashpublications.org/bloodadvances/article/4/15/3754/461773/Stem-cell-transplantation-for-children-with
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society of Hematology
publisher.none.fl_str_mv American Society of Hematology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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