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

Hemophagocytic Lymphohistiocytoses, Lymphoma

Flow Cytometry, T cell activation, lymphoma, HLH

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.

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).

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