Children and Adult Hemophagocytic Syndrome (HLHa) (HLH-genes)

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.

Study Overview

• Status: Completed
• Conditions: Hemophagocytic Syndrome
• Intervention / Treatment: Biological: Identification of biological markers

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 Type: Observational
• Enrollment (Actual): 204

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

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

Description

Inclusion Criteria:

Major criteria:

• hemophagocytosis found in a specimen histology.
• Fever
• Splenomegaly

Minor criteria:

• 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
• 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)

Exclusion Criteria:

• Pregnant women
• A person under guardianship
• Patients under the age of 2 years

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hemophagocytic syndrome; patient with hemophagocytic syndrome	Biological: Identification of biological markers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	T0 (before traitment
name of treatment	administrated treatments	T2 (T2 is the first day of treatment)
Clinicals criteria	clinicals description of patients : Fever, Splenomegaly and adenopathy	T0
biologicals criteria	measure of : cytokines expression Hemoglobin level number of Platelets number of Neutrophils number of triglycerides> number of fibrinogen number of Ferritin	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	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	T4 (6 /12 months after the resolution of HLH)
Clinicals criteria	clinicals description of patients : Fever, Splenomegaly and adenopathy	T1(T1 is the first day of HLH syndrome)
Clinicals criteria	clinicals description of patients : Fever, Splenomegaly and adenopathy	T2 (T2 is the first day of treatment)
Clinicals criteria	clinicals description of patients : Fever, Splenomegaly and adenopathy	T4 6 /12 months after the resolution of HLH)
name of treatment	administrated treatments	T4(6/12 month after resolution of HLH)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Laboratory of normal and pathological development Immune System - IFR 94 U768; Reference Centre for Hereditary Immunodeficiency: CEREDIH
• Investigators: Principal Investigator: Olivier Hermine, MD, PhD, Hopital Necker Enfants Malades, Assistance Publique des Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 12, 2017

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Hemophagocytic lymphohistiocytosis; infant, adolescent and adult Hemophagocytic Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Lymphatic Diseases; Disease; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Syndrome; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: NI10015; AOM 10219