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
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/156554
Ver los metadatos del registro completo
| id |
CONICETDig_7f6d30a5270fff820de9971f62f919fc |
|---|---|
| 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 Técnicas2025-10-22T11:09:33Zoai: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:34982025-10-22 11:09:34.052CONICET 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) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
| reponame_str |
CONICET Digital (CONICET) |
| collection |
CONICET Digital (CONICET) |
| 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 |
| _version_ |
1846781443538157568 |
| score |
12.982451 |