Hemophagocytic SyndromeHLH-genesNCT02113917
Children and Adult Hemophagocytic Syndrome (HLHa)
An observational study of Hemophagocytic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Different study of HLHa patients : Diagnosis criteria, because criteria are based on pediatric genetic studies. Physiopathological studies: genetic studies have demonstrated the role of CD8+ cells, in particular because they have a genetic defect affecting their cytotoxic functions in HLH pediatric. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Hemophagocytic Syndrome
- What is being tested?
- Identification of biological markers
- How many people
- 204 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2010to 12 Jan 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Infant, Adolescent and adult patients who have a HLH syndrome regardless of etiology, hospitalized in Internal Medicine, Critical Care, Hematology, Rheumatology Neurology or Organ Transplantation
Who may be able to join
- Major criteria:
- hemophagocytosis found in a specimen histology.
- Fever
- Splenomegaly
- Minor criteria:
- adenopathy
Show all 11Show fewer
- cytopenia> 2 cell lines Hemoglobin <9 g / dl (less than 4 weeks and> 12 g / dl) Platelets <100 000 x 10 / l Neutrophils <1 10 / l
- hypertriglyceridaemia and / or hypofibrinogenaemia Elevated triglycerides> 3 mmol / l Fibrinogen <1.5 g / l
- Ferritin> 500 microg / L
- These criteria will be those used for the diagnosis of HLH in adults:
- One major criterion and two minor (including hyper ferritin or hypertriglyceridemia) 3 minor criteria (including hyper ferritin or hypertriglyceridemia)
Who cannot join
- Pregnant women
- A person under guardianship
- Patients under the age of 2 years
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Formation of a Cohort of HLHa Patients in Order to Study Their Physiopathological Characteristics
Different study of HLHa patients :
- Diagnosis criteria, because criteria are based on pediatric genetic studies.
- Physiopathological studies: genetic studies have demonstrated the role of CD8+ cells, in particular because they have a genetic defect affecting their cytotoxic functions in HLH pediatric. the aim is to establish if the same defect is found in both some or in all of HLHa patients. If this is the case, to then establish whether hypomorphic genetic mutations are responsible.
Read the detailed description
Formation of a prospective and retrospective infant, adolescent and adult HLH patients cohort.
Collection of clinical and biological, therapeutics, informations, in a register, The collection of information is:
- To identify clinical and biological criteria specific to HLHa
- Classify patients into homogeneous groups, based on clinical biological scalability in particular, with regards to their response to treatment
- Identify and analyze the behavioral therapy Creation of a bank of biological samples for use in the study of the pathophysiology of HLHa.
Background:
The hemophagocytic syndrome in infant, adolescent and adults (HLH) is a serious and often lethal condition. The study of literature series HLHa shows that these syndromes frequently develop in immunocompromised patients (renal transplant, HIV, collagen in Processing immunosuppressants) in the course of a viral infection. HLH syndrome has also been described as a clinical form of lymphoma or connective disease (lupus). These clinical forms are rare, severe and recurrent suggesting the possibility that immune deficiency could be involved. The study of pediatric forms has definitely established a link between HLH syndrome and the presence of immune deficiency by identifying the nature of the latter. Four genetically determined diseases are manifested by HLH syndrome. These conditions are Family lymphohistiocytosis (LHF) syndrome, Chediak-Higashi CHS syndrome, Griscelli (GS) type 2 syndromes and X-linked lymphoproliferative (XLP 1 and 2). The mutated genes are respectively perforin Unc 13.4 and syntaxin in the LHF2, 3, 4 (10q locus genetic for LHF 1), CHS1/LYST (Lysosomal Trafficking regulator) in the CHS, in the Rab27a GS type 2, and XIAP and SH2D1A in the XLP. It is now well established that proteins encoded by these genes are necessary for the cytotoxic function of CD8 + and in the absence of these proteins is the cytotoxocity CD8 + deficient. Also, closed clinical and biological characteristics shared by pediatric genetic and adult forms suggest the existence of immune defects responsible for some or all HLH adult patients.
- Conditions
- Hemophagocytic Syndrome
- Being tested
- Identification of biological markers
- Keywords
- infant, adolescent and adult Hemophagocytic Syndrome, Hemophagocytic lymphohistiocytosis
- Medical subject headings
- Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Identification of biological markersBiological
| Study group | Role | What they receive |
|---|---|---|
| hemophagocytic syndrome | patient with hemophagocytic syndrome Receives: Biological: Identification of biological markers |
What is being measured
The primary outcome is the main question the study is designed to answer.
biologicals criteria
measure of : cytokines expression (mmol/L) Hemoglobin (g/dl) number of Platelets (number/L) number of Neutrophils (number/L) number of triglycerides (mmol/L) number of fibrinogen (g/L) number of Ferritin (microg/L)
Measured: T0 (before traitment
name of treatment
administrated treatments
Measured: T2 (T2 is the first day of treatment)
Clinicals criteria
clinicals description of patients : Fever, Splenomegaly and adenopathy
Measured: T0
biologicals criteria
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
Measured: T1 (T1 is the first day of HLH syndrome)
biologicals criteria
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
Measured: T2 (T2 is the first day of treatment)
biologicals criteria
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
Measured: T4 (6 /12 months after the resolution of HLH)
Clinicals criteria
clinicals description of patients : Fever, Splenomegaly and adenopathy
Measured: T1(T1 is the first day of HLH syndrome)
Clinicals criteria
clinicals description of patients : Fever, Splenomegaly and adenopathy
Measured: T2 (T2 is the first day of treatment)
Clinicals criteria
clinicals description of patients : Fever, Splenomegaly and adenopathy
Measured: T4 6 /12 months after the resolution of HLH)
name of treatment
administrated treatments
Measured: T4(6/12 month after resolution of HLH)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study startJan 2010
- Primary completionJan 2016
- Study completion12 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hemophagocytic SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 204 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Laboratory of normal and pathological development Immune System - IFR 94 U768, Reference Centre for Hereditary Immunodeficiency: CEREDIH, URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Olivier Hermine, MD, PhD, Principal investigator, Hopital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02113917
- Sponsor's protocol ID
- NI10015
- Other IDs
- AOM 10219
- Acronym
- HLH-genes
- Status last verified
- Sep 2025
- First submitted
- 24 May 2013
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Bloch C, Chhun S, Sritharan N, Gil M, Lhote R, Boubaya M, Lambotte O, Launay D, Larroche C, Lazaro E, Liffermann F, Michel M, Michot JM, Morel P, Terriou L, Urbansk G, Viallard JF, Cheminant M, Suarez F, Lepelletier Y, de Saint Basile G, Hermine O; French HLH Study Group. The IL-10/IL-6 Ratio and the Risk Score: Two Cytokines-Based Predictors for Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adults (M-HLHa). Am J Hematol. 2026 Sep;101(9):2214-2224. doi: 10.1002/ajh.70410. Epub 2026 Jun 16.
PubMed 42299056Bloch C, Jais JP, Gil M, Boubaya M, Lepelletier Y, Bader-Meunier B, Mahlaoui N, Garcelon N, Lambotte O, Launay D, Larroche C, Lazaro E, Liffermann F, Lortholary O, Michel M, Michot JM, Morel P, Cheminant M, Suarez F, Terriou L, Urbanski G, Viallard JF, Alcais A, Fischer A, de Saint Basile G, Hermine O; French HLH Study Group. Severe adult hemophagocytic lymphohistiocytosis (HLHa) correlates with HLH-related gene variants. J Allergy Clin Immunol. 2024 Jan;153(1):256-264. doi: 10.1016/j.jaci.2023.07.023. Epub 2023 Sep 9.
PubMed 37678575
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Formation of a Cohort of HLHa Patients in Order to Study Their Physiopathological Characteristics
- ClinicalTrials.gov ID
- NCT02113917
- Acronym / sponsor ID
- HLH-genes / NI10015
- Conditions
- Hemophagocytic Syndrome
- Keywords
- infant, adolescent and adult Hemophagocytic Syndrome, Hemophagocytic lymphohistiocytosis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 204 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Laboratory of normal and pathological development Immune System - IFR 94 U768, Reference Centre for Hereditary Immunodeficiency: CEREDIH, URC-CIC Paris Descartes Necker Cochin
- Study start
- Jan 2010
- Primary completion
- Jan 2016 (actual)
- Study completion
- 12 Jan 2017 (actual)
- First posted
- 15 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Different study of HLHa patients :
- Diagnosis criteria, because criteria are based on pediatric genetic studies.
- Physiopathological studies: genetic studies have demonstrated the role of CD8+ cells, in particular because they have a genetic defect affecting their cytotoxic functions in HLH pediatric. the aim is to establish if the same defect is found in both some or in all of HLHa patients. If this is the case, to then establish whether hypomorphic genetic mutations are responsible.
Detailed description
Formation of a prospective and retrospective infant, adolescent and adult HLH patients cohort.
Collection of clinical and biological, therapeutics, informations, in a register, The collection of information is:
- To identify clinical and biological criteria specific to HLHa
- Classify patients into homogeneous groups, based on clinical biological scalability in particular, with regards to their response to treatment
- Identify and analyze the behavioral therapy Creation of a bank of biological samples for use in the study of the pathophysiology of HLHa.
Background:
The hemophagocytic syndrome in infant, adolescent and adults (HLH) is a serious and often lethal condition. The study of literature series HLHa shows that these syndromes frequently develop in immunocompromised patients (renal transplant, HIV, collagen in Processing immunosuppressants) in the course of a viral infection. HLH syndrome has also been described as a clinical form of lymphoma or connective disease (lupus). These clinical forms are rare, severe and recurrent suggesting the possibility that immune deficiency could be involved. The study of pediatric forms has definitely established a link between HLH syndrome and the presence of immune deficiency by identifying the nature of the latter. Four genetically determined diseases are manifested by HLH syndrome. These conditions are Family lymphohistiocytosis (LHF) syndrome, Chediak-Higashi CHS syndrome, Griscelli (GS) type 2 syndromes and X-linked lymphoproliferative (XLP 1 and 2). The mutated genes are respectively perforin Unc 13.4 and syntaxin in the LHF2, 3, 4 (10q locus genetic for LHF 1), CHS1/LYST (Lysosomal Trafficking regulator) in the CHS, in the Rab27a GS type 2, and XIAP and SH2D1A in the XLP. It is now well established that proteins encoded by these genes are necessary for the cytotoxic function of CD8 + and in the absence of these proteins is the cytotoxocity CD8 + deficient. Also, closed clinical and biological characteristics shared by pediatric genetic and adult forms suggest the existence of immune defects responsible for some or all HLH adult patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hemophagocytic syndrome | – | Biological: Identification of biological markerspatient with hemophagocytic syndrome |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Infant, Adolescent and adult patients who have a HLH syndrome regardless of etiology, hospitalized in Internal Medicine, Critical Care, Hematology, Rheumatology Neurology or Organ Transplantation
Key inclusion criteria (11 listed)
- hemophagocytosis found in a specimen histology.
- Fever
- Splenomegaly
- adenopathy
- cytopenia> 2 cell lines Hemoglobin <9 g / dl (less than 4 weeks and> 12 g / dl) Platelets <100 000 x 10 / l Neutrophils <1 10 / l
Key exclusion criteria (3 listed)
- Pregnant women
- A person under guardianship
- Patients under the age of 2 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Identification of biological markers | Biological | hemophagocytic syndrome |
Primary outcome
biologicals criteria
Time frame: T0 (before traitment
measure of : cytokines expression (mmol/L) Hemoglobin (g/dl) number of Platelets (number/L) number of Neutrophils (number/L) number of triglycerides (mmol/L) number of fibrinogen (g/L) number of Ferritin (microg/L)
name of treatment
Time frame: T2 (T2 is the first day of treatment)
administrated treatments
Clinicals criteria
Time frame: T0
clinicals description of patients : Fever, Splenomegaly and adenopathy
biologicals criteria
Time frame: T1 (T1 is the first day of HLH syndrome)
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
biologicals criteria
Time frame: T2 (T2 is the first day of treatment)
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
biologicals criteria
Time frame: T4 (6 /12 months after the resolution of HLH)
measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin
Clinicals criteria
Time frame: T1(T1 is the first day of HLH syndrome)
clinicals description of patients : Fever, Splenomegaly and adenopathy
Clinicals criteria
Time frame: T2 (T2 is the first day of treatment)
clinicals description of patients : Fever, Splenomegaly and adenopathy
Clinicals criteria
Time frame: T4 6 /12 months after the resolution of HLH)
clinicals description of patients : Fever, Splenomegaly and adenopathy
name of treatment
Time frame: T4(6/12 month after resolution of HLH)
administrated treatments
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Derived from this study: PubMed 42299056Bloch C, Chhun S, Sritharan N, Gil M, Lhote R, Boubaya M, Lambotte O, Launay D, Larroche C, Lazaro E, Liffermann F, Michel M, Michot JM, Morel P, Terriou L, Urbansk G, Viallard JF, Cheminant M, Suarez F, Lepelletier Y, de Saint Basile G, Hermine O; French HLH Study Group. The IL-10/IL-6 Ratio and the Risk Score: Two Cytokines-Based Predictors for Malignancy-Associated Hemophagocytic Lymphohistiocytosis in Adults (M-HLHa). Am J Hematol. 2026 Sep;101(9):2214-2224. doi: 10.1002/ajh.70410. Epub 2026 Jun 16.
- Derived from this study: PubMed 37678575Bloch C, Jais JP, Gil M, Boubaya M, Lepelletier Y, Bader-Meunier B, Mahlaoui N, Garcelon N, Lambotte O, Launay D, Larroche C, Lazaro E, Liffermann F, Lortholary O, Michel M, Michot JM, Morel P, Cheminant M, Suarez F, Terriou L, Urbanski G, Viallard JF, Alcais A, Fischer A, de Saint Basile G, Hermine O; French HLH Study Group. Severe adult hemophagocytic lymphohistiocytosis (HLHa) correlates with HLH-related gene variants. J Allergy Clin Immunol. 2024 Jan;153(1):256-264. doi: 10.1016/j.jaci.2023.07.023. Epub 2023 Sep 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier Hermine, MD, PhD principal investigator
Hopital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hemophagocytic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
biologicals criteria (time frame: T0 (before traitment). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02113917, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.