Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis

Simple item page
dc.contributor.authorChinn, Ivan K.
dc.contributor.authorEckstein, Olive S.
dc.contributor.authorPeckham-Gregory, Erin C.
dc.contributor.authorGoldberg, Baruch R.
dc.contributor.authorForbes, Lisa R.
dc.contributor.authorNicholas, Sarah K.
dc.contributor.authorMace, Emily M.
dc.contributor.authorVogel, Tiphanie P.
dc.contributor.authorAbhyankar, Harshal A.
dc.contributor.authorDiaz, Maria I.
dc.contributor.authorHeslop, Helen E.
dc.contributor.authorKrance, Robert A.
dc.contributor.authorMartinez, Caridad A.
dc.contributor.authorNguyen, Trung C.
dc.contributor.authorBashir, Dalia A.
dc.contributor.authorGoldman, Jordana R.
dc.contributor.authorStray-Pedersen, Asbjørg
dc.contributor.authorPedroza, Luis A.
dc.contributor.authorPoli, Cecilia
dc.contributor.authorAldave-Becerra, Juan C.
dc.contributor.authorMcGhee, Sean A.
dc.contributor.authorAl-Herz, Waleed
dc.contributor.authorChamdin, Aghiad
dc.contributor.authorCoban-Akdemir, Zeynep H.
dc.contributor.authorJhangiani, Shalini N.
dc.contributor.authorMuzny, Donna M.
dc.contributor.authorCao, Tram N.
dc.contributor.authorHong, Diana N.
dc.contributor.authorGibbs, Richard A.
dc.contributor.authorLupski, James R.
dc.contributor.authorOrange, Jordan S.
dc.contributor.authorMcClain, Kenneth L.
dc.contributor.authorAllen, Carl E.
dc.date.accessioned2021-08-30T17:18:20Z
dc.date.available2021-08-30T17:18:20Z
dc.date.issued2018
dc.description.abstractThe HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically or through research-based whole-exome sequencing. Clinical metrics were analyzed with respect to genomic results. Of 122 subjects enrolled over the course of 17 years, 101 subjects received genetic testing. Biallelic familial HLH (fHLH) gene defects were identified in only 19 (19%) and correlated with presentation at younger than 1 year of age (P < .0001). Digenic fHLH variants were observed but lacked statistical support for disease association. In 28 (58%) of 48 subjects, research whole-exome sequencing analyses successfully identified likely molecular explanations, including underlying primary immunodeficiency diseases, dysregulated immune activation and proliferation disorders, and potentially novel genetic conditions. Two-thirds of patients identified by the HLH-2004 criteria had underlying etiologies for HLH, including genetic defects, autoimmunity, and malignancy. Overall survival was 45%, and increased mortality correlated with HLH triggered by infection or malignancy (P < .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.es
dc.identifier.citationBlood . 2018 Jul 5;132(1):89-100es
dc.identifier.urihttps://doi.org/10.1182/blood-2017-11-814244es
dc.identifier.urihttp://hdl.handle.net/11447/4529
dc.language.isoenes
dc.subjectPhagocyteses
dc.subjectGranulocyteses
dc.subjectMyelopoiesises
dc.titleGenetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosises
dc.typeArticlees

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis.pdf
Size:
1.07 MB
Format:
Adobe Portable Document Format
Description:
Texto Completo
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services