Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study

NCT06339177 | Recruiting

• 2 other identifiers: 10001899001899-I
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by disrupted immune function. People with HLH are prone to fevers and illnesses, which can be fatal. Some people develop a genetic form of this disease (pHLH), but researchers do not understand why some other people develop a nongenetic form (sHLH). They also do not have good ways to diagnose and treat sHLH. Objective: To learn about sHLH and why some people get it and others do not. Eligibility: Adults aged 18 years and older with sHLH. Design: Participants will be admitted to the study based on a review of their medical records. Those who join will have at least 3 clinical evaluations over 9 to 12 months. These may occur during an inpatient hospitalization if they require medical care or in the outpatient clinic. Participants will also have a physical exam at each visit. Up to half a cup of blood will be drawn at each visit. Participants may also have their blood drawn by their own doctors, who will send the samples to the researchers. Researchers may also contact these participants by telephone or video calls. The blood will be used for clinical tests as well as research. No new treatments will be administered as part of this study; however, standard medications and treatments may be recommended. Participants may opt to continue their visits once a year for 3 more years. Participants may also opt for an extra clinial evaluation 1 week after starting a new treatment. ...

Conditions

Lymphohistiocytosis, Hemophagocytic; Secondary Hemophagocytic Lymphohistiocytosis; Hyperinflammatory Syndromes; Macrophage Activation Syndrome

Keywords

Hemophagocytic Lymphohistiocytosis; HLH; Macrophage Activation Syndrome; MAS; Cytokine Storm Syndrome; Hyperinflammatory Syndrome; Hyperinflammation; Still's Disease; Hyperferritinemia; Immune Dysregulation

Outcome Measures

Primary Outcomes (1)

• Identify immunologic mechanisms involved in the pathogenesis of sHLH from a variety of predisposing conditions.

  To study the immunopathogenesis of sHLH from various etiologies including biomarkers, cellular phenotypes, and gene expression to determine mechanistic pathways that may be amenable to host-directed therapies.

  Through end of study.

Secondary Outcomes (4)

• Prospectively define acute and longitudinal clinical profiles that predict key clinical outcomes.

  Through end of study.

• Compare clinical and immune profiles between the classically defined HLH subgroups.

  Through end of study.

• Improve the understanding of the pathogenesis of sHLH.

  Through end of study.

• Characterize risk factors to identify populations at risk for developing sHLH.

  Through end of study.

Study Arms (1)

sHLH

Hemophagocytic lymphohistiocytosis (HLH) represents a clinical condition of persistent, dysregulated immune activation with unrelenting fevers, hyperferritinemia, and cytopenias, which lead to multiorgan failure and death.

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult participants with active secondary HLH by meeting any published criteria. Hemophagocytic lymphohistiocytosis (HLH) represents a clinical condition of persistent, dysregulated immune activation with unrelenting fevers, hyperferritinemia, and cytopenias, which lead to multiorgan failure and death.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

RECRUITING

Related Publications (4)

• Rocco JM, Laidlaw E, Galindo F, Anderson M, Sortino O, Kuriakose S, Lisco A, Manion M, Sereti I. Mycobacterial Immune Reconstitution Inflammatory Syndrome in HIV is Associated With Protein-Altering Variants in Hemophagocytic Lymphohistiocytosis-Related Genes. J Infect Dis. 2023 Jul 14;228(2):111-115. doi: 10.1093/infdis/jiad059.

  PMID: 37040388 BACKGROUND

• Rocco JM, Laidlaw E, Galindo F, Anderson M, Rupert A, Higgins J, Sortino O, Ortega-Villa AM, Sheikh V, Roby G, Kuriakose S, Lisco A, Manion M, Sereti I. Severe Mycobacterial Immune Reconstitution Inflammatory Syndrome (IRIS) in Advanced Human Immunodeficiency Virus (HIV) Has Features of Hemophagocytic Lymphohistiocytosis and Requires Prolonged Immune Suppression. Clin Infect Dis. 2023 Feb 8;76(3):e561-e570. doi: 10.1093/cid/ciac717.

  PMID: 36048425 BACKGROUND

• Shakoory B, Geerlinks A, Wilejto M, Kernan K, Hines M, Romano M, Piskin D, Ravelli A, Sinha R, Aletaha D, Allen C, Bassiri H, Behrens EM, Carcillo J, Carl L, Chatham W, Cohen JI, Cron RQ, Drewniak E, Grom AA, Henderson LA, Horne A, Jordan MB, Nichols KE, Schulert G, Vastert S, Demirkaya E, Goldbach-Mansky R, de Benedetti F, Marsh RA, Canna SW; HLH/MAS task force. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ann Rheum Dis. 2023 Oct;82(10):1271-1285. doi: 10.1136/ard-2023-224123. Epub 2023 Jul 24.

  PMID: 37487610 BACKGROUND

• Jordan MB, Allen CE, Greenberg J, Henry M, Hermiston ML, Kumar A, Hines M, Eckstein O, Ladisch S, Nichols KE, Rodriguez-Galindo C, Wistinghausen B, McClain KL. Challenges in the diagnosis of hemophagocytic lymphohistiocytosis: Recommendations from the North American Consortium for Histiocytosis (NACHO). Pediatr Blood Cancer. 2019 Nov;66(11):e27929. doi: 10.1002/pbc.27929. Epub 2019 Jul 24.

  PMID: 31339233 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Cytokine Release Syndrome; Arthritis, Juvenile; Hyperferritinemia

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Joseph M Rocco, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph M Rocco, M.D.

CONTACT

(301) 312-2858; joseph.rocco@nih.gov

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: April 1, 2024
• Study Start: July 2, 2024
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): April 1, 2031
• Last Updated: March 20, 2026

Record last verified: 2026-03-18

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Upon completion of the protocol/upon publication.
• Access Criteria: Data will only be available upon request, the PI will review and approve requests for data.

Locations

US (2)