Impact of Ultra-fast Genetic Diagnosis of Familial Lymphohistiocytosis on the Time to Bone Marrow Transplantation and Overall Survival

NCT07741747 | Not Yet Recruiting

• 2 other identifiers: RCAPHM25_05672026-A00463-48
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Familial lymphohistiocytosis (FHL) is a group of rare genetic diseases (around fifteen cases per year in France). The defect in T lymphocyte cytotoxicity resulting from this disease is responsible for hemophagocytic lymphohistiocytosis (HLH). Promptly treatment of HLH is essential for prognosis. These diseases are fatal without a bone marrow transplant, with an overall 5-year survival rate of no more than 80% for FHL. The genetic or acquired nature of HLH is not easy to determine. An infectious trigger can be confounding when it occurs in an FHL. But above all, functional biological tests demonstrating a T lymphocyte cytotoxicity defects are difficult to interpret. Genetic diagnosis is therefore essential for confirming the primary nature of HLH, and for initiating targeted treatments (first stage: putting HLH into remission with chemotherapy or immunotherapy; second stage: bone marrow transplant). Genetic diagnosis of FHL is therefore a matter of emergency, and is currently based on targeted gene panel exploration (fragmentation sequencing) requiring 6 to 8 weeks. Recently, the development of third-generation sequencing (TGS) has revolutionized genomic medicine, enabling unitary sequencing in real time. As a result of this innovation, certain private molecular diagnostic specialties can now access this new emergency genomic medicine. Aim: the main aim of this study is to demonstrate the feasibility of a national circuit for ultra-rapid genetic diagnosis of pediatric HLH revealing familial lymphohistiocytosis. The secondary objective is to evaluate the impact of this early genetic diagnosis on the delay to remission of HLH and the delay to transplantation. Methods: This prospective, multicenter study measures the time required for genetic diagnosis of FHL in pediatric HLH, using innovative TGS sequencing technology. Perspectives: Fast genomic diagnosis of FHL will considerably shorten the time to confirm the diagnosis, to obtain HLH remission and, finally, to reach transplantation faster.

Conditions

Lymphohistiocytosis; Familial Lymphohistiocytosis

Keywords

Lymphohistiocytosis; Rare disease; Fast-genomic; Precision medecin; Bone marrow transplant

Outcome Measures

Primary Outcomes (1)

• Time (in days) from clinical suspicion to hematopoietic stem cell transplantation

  From enrollment until 24 months post transplantation

Secondary Outcomes (9)

• Proportion of patients completing the full diagnostic pathway

  From enrollment until 24 months post transplantation

• Time from clinical suspicion to receipt of the genetic result (in days)

  From enrollment until 24 months post transplantation

• Time from clinical suspicion to initiation of specific immunomodulatory therapy (in days)

  From enrollment until 24 months post transplantation

• Overall survival

  From enrollment until 6, 12 and and 24 months post transplation

• Total length of hospital stays (in days)

  From enrollment until 24 months post transplantation

Study Arms (2)

Prospectif Group

EXPERIMENTAL

Group of 200 patients who will be tested prospectively

Diagnostic Test: Third-generation sequencing

Retrospectif Group

NO INTERVENTION

Group of 40 patients whose data will be retrospectivly compared to the prospectif group

Interventions

Third-generation sequencing DIAGNOSTIC_TEST

Blood sample will be collected in order to perform the third-generation sequencing testing which sould give results in a 5 day delay, instead of 6-8 weeks (standard testing)

Prospectif Group

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children under 18 years old
• Confirmed or suspected diagnosis of FHL or a related genetic syndrome predisposing to HLH (e.g. Griscelli Syndrome, Chédiak-Higashi Syndrome, XLP1, XLP2) or a family history of lymphohistiocytic activation syndrome
• Presence of at least 5 of the 8 following criteria (diagnostic criteria according to the definition of the "Histiocyte Society" (1)):
• Fever
• Splenomegaly
• Hypertriglyceridemia ≥ 3 mmol/l and/or hypofibrinogenemia≤ 1.5g/l
• Hemophagocytosis found in a histological sample
• Decreased or absent NK function (\<10% of the laboratory normal)
• Ferritin ≥ 500μg/l
• Soluble CD25 ≥ 2,400U/ml or presence of activated T cells in phenotyping
• Cytopenia (affecting at least two blood cell lines): Haemoglobin \< 9.0 g/dl, Platelets \<100 G/L, Neutrophils \<1,0 G/L
• Patient benefiting from social security coverage
• The legal guardian(s) who have signed the informed consent form

You may not qualify if:

• Age ≥ 18 years
• Solid tumor, leukemia, lymphoma
• Subjects covered by articles L1121-5 to 1121-8 of the public health code (patients under guardianship or curatorship, patient deprived of liberty, pregnant or breadtfeeding woman)
• Persons who do not understand the French language

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead
• Aix Marseille Université: collaborator
• Etablissement Français du Sang: collaborator

Study Sites (1)

Assistance Publique - Hôpitaux de Marseille

Marseille, France

Location

MeSH Terms

Conditions

Rare Diseases

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Vincent BARLOGIS, Pr

CONTACT

04 91 38 98 21; vincent.barlogis@ap-hm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 3, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2030
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)