A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach ≥5 positive criteria...

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Autores principales: Smits, Bas M., van Montfrans, Joris, Merrill, Samuel A., van de Corput, Lisette, van Gijn, Mariëlle, de Vries, Andrica, van den Bos, Cor, Abbink, Floor, van der Molen, Renate G., Dors, Natasja, Lindemans, Caroline, Boelens, Jaap J., Nierkens, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310853/
https://www.ncbi.nlm.nih.gov/pubmed/33779897
http://dx.doi.org/10.1007/s10875-021-01005-7
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author Smits, Bas M.
van Montfrans, Joris
Merrill, Samuel A.
van de Corput, Lisette
van Gijn, Mariëlle
de Vries, Andrica
van den Bos, Cor
Abbink, Floor
van der Molen, Renate G.
Dors, Natasja
Lindemans, Caroline
Boelens, Jaap J.
Nierkens, Stefan
author_facet Smits, Bas M.
van Montfrans, Joris
Merrill, Samuel A.
van de Corput, Lisette
van Gijn, Mariëlle
de Vries, Andrica
van den Bos, Cor
Abbink, Floor
van der Molen, Renate G.
Dors, Natasja
Lindemans, Caroline
Boelens, Jaap J.
Nierkens, Stefan
author_sort Smits, Bas M.
collection PubMed
description Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach ≥5 positive criteria out of the 8 HLH-2004 criteria can be time consuming and may delay timely initiation of treatment. Hence, we applied a data-driven approach to identify a minimal parameter set for early decision-making towards the initiation of HLH-specific treatment. We retrospectively evaluated 165 patients from five Dutch tertiary hospitals with suspected HLH. Sixteen pHLH (median age 0.5 years) and 70 sHLH patients (median age 8.7 years) were identified using the HLH-2004 criteria. Clustering analysis and multi-receiver operator characteristics were used to identify parameters distinctive of HLH. The presence of either increased ferritin, cytopenia in ≥2 lineages, or splenomegaly distinguished HLH from non-HLH cases with a negative predictive value of 100%. A minimal parameter set consisting of 2 major criteria (phagocytosis and splenomegaly) and 3 minor criteria (cytopenia, increased ferritin, and increased triglycerides/low fibrinogen) predicted HLH with 95% (88–99) sensitivity and 94% (86–98) specificity. This finding was replicated in an independent retrospective validation cohort of 109 US patients (n = 109). By dividing a subset of the HLH-2004 criteria into major and minor criteria, this strategy uses the evaluation of less than 5 criteria to quickly identify patients with HLH. When confirmed in a prospective setting, this approach could be of value for timely diagnosis and treatment of HLH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-021-01005-7.
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spelling pubmed-83108532021-08-12 A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis Smits, Bas M. van Montfrans, Joris Merrill, Samuel A. van de Corput, Lisette van Gijn, Mariëlle de Vries, Andrica van den Bos, Cor Abbink, Floor van der Molen, Renate G. Dors, Natasja Lindemans, Caroline Boelens, Jaap J. Nierkens, Stefan J Clin Immunol Original Article Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation syndrome characterized by uncontrolled immune cell activation. Timely diagnosis is important, since early treatment can improve survival rates. However, completing all assessments needed to reach ≥5 positive criteria out of the 8 HLH-2004 criteria can be time consuming and may delay timely initiation of treatment. Hence, we applied a data-driven approach to identify a minimal parameter set for early decision-making towards the initiation of HLH-specific treatment. We retrospectively evaluated 165 patients from five Dutch tertiary hospitals with suspected HLH. Sixteen pHLH (median age 0.5 years) and 70 sHLH patients (median age 8.7 years) were identified using the HLH-2004 criteria. Clustering analysis and multi-receiver operator characteristics were used to identify parameters distinctive of HLH. The presence of either increased ferritin, cytopenia in ≥2 lineages, or splenomegaly distinguished HLH from non-HLH cases with a negative predictive value of 100%. A minimal parameter set consisting of 2 major criteria (phagocytosis and splenomegaly) and 3 minor criteria (cytopenia, increased ferritin, and increased triglycerides/low fibrinogen) predicted HLH with 95% (88–99) sensitivity and 94% (86–98) specificity. This finding was replicated in an independent retrospective validation cohort of 109 US patients (n = 109). By dividing a subset of the HLH-2004 criteria into major and minor criteria, this strategy uses the evaluation of less than 5 criteria to quickly identify patients with HLH. When confirmed in a prospective setting, this approach could be of value for timely diagnosis and treatment of HLH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10875-021-01005-7. Springer US 2021-03-29 2021 /pmc/articles/PMC8310853/ /pubmed/33779897 http://dx.doi.org/10.1007/s10875-021-01005-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Smits, Bas M.
van Montfrans, Joris
Merrill, Samuel A.
van de Corput, Lisette
van Gijn, Mariëlle
de Vries, Andrica
van den Bos, Cor
Abbink, Floor
van der Molen, Renate G.
Dors, Natasja
Lindemans, Caroline
Boelens, Jaap J.
Nierkens, Stefan
A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title_full A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title_fullStr A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title_full_unstemmed A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title_short A Minimal Parameter Set Facilitating Early Decision-making in the Diagnosis of Hemophagocytic Lymphohistiocytosis
title_sort minimal parameter set facilitating early decision-making in the diagnosis of hemophagocytic lymphohistiocytosis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310853/
https://www.ncbi.nlm.nih.gov/pubmed/33779897
http://dx.doi.org/10.1007/s10875-021-01005-7
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