Flow Cytometry for the Study of T-Cell Populations in Hemophagocytic Lymphohistiocytosis Associated With Lymphomas

NCT ID: NCT06585124

Last Updated: 2024-09-05

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 150 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-05-01
• Study Completion Date: 2026-05-01

Brief Summary

The goal of this study is to explore the associations between T cell activation and the occurrence of hemophagocytic lymphohistiocytosis (HLH) in patients with newly diagnosed lymphomas. The specific aims are:

Prediction of Lymphoma-Associated HLH (LA-HLH): Compare flow cytometric T cell activation markers with the H-score to predict LA-HLH.

Identification of new markers for predicting HLH in patients with aggressive lymphoma.

Description of the incidence rate of LA-HLH. Assessment of the outcomes of LA-HLH identified by flow cytometric analysis or the H-score.

This prospective, single-center observational study will include 150 patients newly diagnosed with aggressive lymphoma within one year. Peripheral blood samples will be taken at diagnosis alongside routine blood chemistry tests for flow cytometric analysis of the T-lymphocyte activation profile. Data on disease characteristics will be collected to calculate the H-score, HLH-2004 score, and OHI score for diagnosing HLH. The flow cytometry results will be compared with these scores to evaluate their effectiveness in diagnosing LA-HLH.

Detailed Description

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe syndrome characterized by excessive immune system activation and dysregulation. This leads to an overproduction of cytokines and activation of the histiocytic-macrophage system, potentially resulting in multi-organ failure and death. HLH can be classified into primary and secondary forms. Secondary HLH is often triggered by infections, autoimmune diseases, or neoplasms, with lymphomas being the most frequent neoplastic triggers.

There is limited knowledge about secondary HLH, particularly regarding early diagnosis and optimal management. This project aims to address this gap by analyzing cytotoxic T-cells and cell expression markers using flow cytometry, building on findings from two pediatric studies.

Aggressive onset lymphomas may induce a systemic hyperinflammatory state, complicating the diagnosis of HLH, especially in the presence of concurrent bacterial or viral infections. Given the rarity of HLH and its poor prognosis if not promptly diagnosed, further research is crucial, especially in lymphoma-associated cases.

This study aims to apply T-cell activation profiling, previously demonstrated in pediatric populations, to patients with aggressive Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma to identify HLH-associated cases at onset.

The study aims to include 150 patients diagnosed with aggressive lymphoma within a one-year period A peripheral blood sample, collected alongside routine blood chemistry tests at diagnosis, will be used for the flow cytometric study of the T-lymphocyte activation profile. Data pertaining to disease characteristics will be gathered to calculate diagnostic scores for HLH, including the H-score, HLH-2004 score, and OHI score. The flow cytometry results will then be compared with these score parameters to assess their correlation with the diagnosis of lymphoma-associated HLH (LA-HLH).

Conditions

Lymphoma; Hemophagocytic Lymphohistiocytoses

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Interventions

Flow Cytometry

Study of t cell population in flow cytometry

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Diagnosis at onset of aggressive lymphoma including the following histotypes:

• Hodgkin lymphoma
• Transformed B cell lymphomas;
• Diffuse large B-cell lymphomas (diffuse large B-cell lymphoma NOS; T-cell/histiocyte-rich B-cell lymphoma; High grade B-cell lymphoma/high grade B-cell lymphoma with MYC and BCL2 rearrangement ALK-positive large B-cell lymphoma; Large B-cell lymphoma with IRF4 rearrangement; High grade B-cell lymphoma with 11q alterations; Lymphomatoid granulomatosis; EBV-positive large B-cell lymphoma Large B-cell lymphoma associated with chronic inflammation; Fibrin-associated large B-cell lymphoma; Fluid overload-associated large B-cell lymphoma; Plasmoblastic lymphoma; Immune-privileged site B-cell lymphoma Primary cutaneous leg-type large B-cell lymphoma; Intravascular large B-cell lymphoma; Primary mediastinal large B-cell lymphoma; Mediastinal grey zone lymphoma; High grade NOS B-cell lymphoma)
• Burkitt lymphoma
• KSHV/HHV8 a ssociatedlymphomas
• Lymphomas associated with immunodeficiency or immune dysregulation
• Mature T-cell-derived lymphomas (NOS peripheral T-cell lymphoma; Nodal follicular helper T-cell lymphoma; Anaplastic large cell lymphoma; Nodal and extranodal EBV-positive T/NK-cell lymphomas; Hepatosplenic T-cell lymphoma; Enteropathy-associated intestinal T-cell lymphoma, epitheliotropic monomorphic and NOS; Subcutaneous T-cell lymphoma similar to panniculitis)

3. Informed consent to the use of biologic materials for studies related to the present proposal.

2. Prolonged steroid therapy, defined as lasting more than 15 days or high doses of steroid, exceeding 1 mg/kg

3. Age ≤ 18 years;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan Hohaus, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione Policlinico Universitario A. Gemelli, IRCCS

Locations

Stefan Hohaus

Rome, Lazio, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Stefan Hohaus, MD

Role: CONTACT

stefan.hohaus@unicatt.it

063015 ext. 4180

Flaminia Bellisario, MD

Role: CONTACT

flaminia.bellisario@guest.policlinicogemell.it

063015 ext. 4180

Facility Contacts

Stefan Hohaus, MD

Role: primary

stefan.hohaus@unicatt.it

063015 ext. 4180

Flaminia Bellisario, MD

Role: backup

flaminia.bellisario@guest.policlinicogemelli.it

063015 ext. 4180

Other Identifiers

ID-6536

Identifier Type: -

Identifier Source: org_study_id