Evaluation of secondary hemophagocytic lymphohistiocytosis and its immune mechanisms

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This observational study aims to investigate the immunopathogenesis of secondary hemophagocytic lymphohistiocytosis (sHLH) by conducting detailed clinical evaluations and immunologic assessments over a period of 9 to 12 months. Participants aged 18 and older with a confirmed diagnosis of sHLH will undergo multiple clinical evaluations and blood draws to analyze biomarkers, cellular phenotypes, and gene expression. The study seeks to identify the underlying mechanisms of sHLH and potential pathways for targeted therapies. Data will be collected longitudinally, with options for remote participation and local blood processing.

Why it matters

Who can join: the full rules

* INCLUSION CRITERIA:
* Aged 18 years or older.
* Established diagnosis of sHLH defined by meeting any published criteria, per Table 1:

  * Meeting the HLH-2004 criteria.
  * HScore of \>168. For those without a bone marrow biopsy to evaluate for hemophagocytosis (worth 35 points in the criteria), HScore\>134 will be used.
  * For those with underlying rheumatologic disease: meeting the 2016 American College of Rheumatology criteria for macrophage activation syndrome.
* Agree to storage and sharing of study data and biospecimens for future research use.

Table 1: Published Criteria for HLH

HLH-2004 Criteria:

Molecular diagnosis of HLH OR At least 5 of 8 below criteria:

* Fever (\>38.4 Degrees Celcius)
* Splenomegaly
* Cytopenias affecting \>=2 of 3 lineages: Hgb \<9 g/dL, platelets \<10\^5/microliter, neutrophils \<10\^6/microliter
* Hypertriglyceridemia (\>256 mg/dL) and/or fibrinogen \<1.5 g/L
* Hemophagocytosis on biopsy
* Serum ferritin \>=500 ng/mL
* Increased serum sCD25 (\>2400 U/mL)
* Low or absent NK cell activity

HScore:

Known immunosuppression:

0 (no) or 18 (yes)

Temperature (degrees, Celsius):

0 (\<38.4), 33 (38.4-39.4), 49 (\>39.4)

Organomegaly:

0 (no), 23 (liver/spleen), 38 (both)

Number of cytopenias:

0 (1 lines), 24 (2 lines), 34 (3 lines)

Ferritin (ng/mL):

0 (\<2000), 35 (2000-6000), 50 (\>6000)

Triglycerides (mg/dL):

0 (\<1.5), 44 (1.5-4), 66 (\>4)

Fibrinogen (g/L):

0 (\>2.5), 30 (\<2.5)

AST (IU/mL):

0 (\<30), 19 (\>30)

Hemophagocytosis:

0 (no) or 35 (yes)

Cutoff value=169

ACR 2016-MAS Criteria:

A febrile patient with known or suspected sJIA is classified as having macrophage activation syndrome if the following criteria are met:

Ferritin \>684 ng/mL

AND any 2 of the following:

* Platelets \<=181,000/microliter
* AST \>48 IU/mL
* Triglycerides \>156 mg/dL
* Fibrinogen \<=3.6 g/L

Abbreviations: ACR, American College of Rheumatology; AST, aspartate transaminase; Hgb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; MAS, macrophage activation syndrome; NK, natural killer, sJIA, systemic juvenile idiopathic arthritis.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

* Currently pregnant.
* Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study.

Where it's running

• National Institutes of Health Clinical Center
  Bethesda, Maryland, United States Recruiting
• University of Pittsburgh
  Pittsburgh, Pennsylvania, United States Recruiting

Study contacts

• Principal investigator: Joseph M Rocco, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Joseph M Rocco, M.D.
• Email: joseph.rocco@nih.gov
• Phone: (301) 312-2858

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.