Evaluation of IFNγ and Inflammatory Mediators in Patients With Hemophagocytic Lymphohistiocytosis

Study Overview
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Brief Summary
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This observational study is designed to provide a better understanding of the potential use of interferon gamma (IFNγ) and IFNγ-inducible chemokines as markers of HLH disease activity in adults, and the potential of IFNγ to represent a therapeutic target.

Detailed Description
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This is a observational study designed to determine the levels of pro-inflammatory markers in adult patients diagnosed with HLH and to assess the relationship between the biomarkers and disease activity in these patients during the HLH course. Inflammatory markers include IFNγ and IFNγ-induced chemokines C-X-C chemokine ligand 9 and C-X-C chemokine ligand 10. In addition to the blood samples for the biomarker analysis, relevant information gathered by the treating physician will be collected in a data collection form. Whenever possible, collection of serum samples for biomarker analysis and relevant information should occur at HLH diagnosis, at regular time intervals during the treatment course (not more than once a week) up to resolution of HLH. Blood samples will also be sent to the study sponsor (NovImmune S.A.) for cytokine testing. Before patient's samples are sent to the sponsor for testing, patient's name and any personal identifying information will be coded to protect participant's privacy.

Official Title
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An Observational, Multicenter Study to Evaluate Levels of Interferon Gamma (IFNγ) and Other Inflammatory Mediators in Adult Patients With Hemophagocytic Lymphohistiocytosis (A-HLH)

Conditions
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Hemophagocytic Lymphohistiocytoses

Intervention / Treatment
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* Other: Blood Draws Data Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients >=18 years old diagnosed with active HLH as established by the treating physician. HLH forms of unknown origin or secondary to infections or rheumatologic disorders. Should the diagnosis of primary HLH or malignancy become apparent after inclusion, the data collected will be analyzed separately as additional cohorts. The patient must have consented to the use of their clinical data for research purposes at the site. Exclusion Criteria: Patients with primary HLH (diagnosed by the presence of homozygous mutations in a known HLH causative gene) and secondary HLH due to malignancy are excluded.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| A-HLH Patients<br>Patients diagnosed with A-HLH. The diagnosis of A-HLH was established by the treating physician. | Other: Blood Draws Data Collection<br> <br> |
| Malignancy-Associated Hemophagocytic Lymphohistiocytosis (M-HLH) Patients<br>Patients diagnosed with HLH in the context of a malignancy. The diagnosis of M-HLH was established by the treating physician. | Other: Blood Draws Data Collection<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentrations of Inflammatory Markers in Participants Diagnosed With HLH | Serum samples were collected to determine the concentration of C-X-C chemokine ligand 10, C-X-C chemokine ligand 9, interferon gamma, interleukin 10, interleukin 1 beta, interleukin 6, neopterin, tumor necrosis factor alpha, Total human interferon gamma, soluble CD163 and soluble interleukin-2 receptor alpha. | 11 months | 
| Correlation Between Serum Concentrations of Inflammatory Markers and Markers of Disease Activity in Participants Diagnosed With HLH | Serum samples were collected to determine the markers of disease activity as indicated by the following laboratory assessments: albumin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, basophils, beta 2-microglobulin, total and conjugated bilirubin, blood urea nitrogen, serum creatinine, C-reactive protein, D-dimers, hemoglobin, hematocrit, red blood cells, white blood cells, and differential count, platelets, fasting triglycerides, ferritin, fibrinogen, lactate dehydrogenase, natural killer cell activity, prothrombin time and activated partial thromboplastin time, serum immunoglobulin G, Sodium. | 11 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophagocytic Lymphohistiocytosis, Interferon Gamma, IFNγ, Biomarkers, Inflammatory Markers