Studying why some adults develop non-genetic hemophagocytic lymphohistiocytosis
Follows adults with secondary hemophagocytic lymphohistiocytosis to learn why some people develop it.
Key facts
- Who runs it
- National Institute of Allergy and Infectious Diseases (NIAID)
- Where
- Bethesda and Pittsburgh, United StatesSee the 2 sites
- Trial code
- Registry title
- Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
- Status
- Recruiting
- People taking part
- 300 people, planned
- Started
- 2 Jul 2024
- Expected to end
- 1 Apr 2031
- Type of study
- Observational
- Record updated
- 5 November 2026
Who can take part
- Age
- 18 years to 120 years
- Sex
- Women and men
- Healthy volunteers
- Cannot take part
The registry criteria, word for word
Show all 19 criteriaShow less
Who cannot take part
- 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
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Currently pregnant
Other criteria
- 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
Check if you might fit
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- Are you between 18 and 120 years old?
Where in United States
- National Institutes of Health Clinical CenterBethesda, United StatesContact: NIH Clinical Center Office of Patient Recruitment (OPR)Taking people
- University of PittsburghPittsburgh, United StatesContact: Daniella Schwartz, M.D.Taking people
About the trial
What the trial wants to find out
Background:
Read full original descriptionShow less
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.
...
The group in the trial
- 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.
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorData and sources
- Registry record
- Listed on ClinicalTrials.gov.
- Official title
- Hemophagocytic Lymphohistiocytosis (HLH) Evaluation and Research of Clinical, ImmUnoLogic and TranscriptomE Study
- Plain-language title
- Studying why some adults develop non-genetic hemophagocytic lymphohistiocytosisGenerated from the registry record. The registry title is the official one.
- Fit questions
- Built from NCT06339177, who can take part
- Record updated
- 5 November 2026