Description of the Immune Deficiency in Patients With Untreated Chronic Lymphocytic Leukemia and Search for Predictive Factors of Infectious Risk

Chronic Lymphocytic Leukemia (CLL) is a monoclonal B-cell proliferation and the most common leukemia of adults. It is characterized by infiltration of the bone marrow, lymph nodes and blood by small mature lymphocytes. It is an incurable pathology but its evolution is extremely heterogeneous. Thus, some patients will have a life expectancy close to normal without treatment, while for others, a progression of the disease will require the introduction of a specific treatment.

One of the main characteristics of CLL is the associated immune dysfunction. The presence of an increased risk of infectious complications has been clearly demonstrated, even in patients with indolent forms of the disease. Immunosuppression is multifactorial, affecting both humoral and cellular immunity. Nevertheless, the major abnormality associated with infectious risk in CLL is hypogammaglobulinemia. Hypogammaglobulinemia is present in approximately 20% of patients at diagnosis and worsens during the course of the disease. In particular, it is responsible for an impaired vaccine response and the occurrence of encapsulated bacterial infections. As with primary humoral immunodeficiency, chronic humoral immunodeficiency secondary to CLL is associated with the development of irreversible bronchiectasis, the prevalence of which is not well understood, and which increases the risk of severe respiratory infectious complications.

In CLL patients, the normal B lymphocyte compartment and in particular certain populations of interest such as the memory B lymphocyte populations have only been studied to a limited extent. Similarly, there is little data on follicular helper T cells (TfH cells) which play a key role in the acquisition of anti-infectious and particularly post-vaccination immunity.

The primary objective of this study is to analyze the distribution of non-tumor lymphocyte subpopulations in patients with untreated CLL

The secondary objectives of the research are:

1. To prospectively assess the frequency and severity of infections in patients with CLL
2. To search for an association between biological and particularly immunophenotypic data and the occurrence of infections
3. To define the prevalence of bronchiectasis in CLL patients
4. To study the clinical, immunological and biochemical factors associated with the presence of bronchiectasis in CLL patients

75 untreated CLL patients will be included in this study. Thoracic CT scan and immunophenotyping will be performed at inclusion. Infectious complications will be collected prospectively through a follow-up booklet provided to the patient at the time of inclusion. All infections requiring at least one consultation with the general practitioner will be collected. Reported infections will be graded according to a classification derived from the CTCAE.

Our study should help to better characterize the immune deficiency associated with CLL through the analysis of lymphocyte subpopulations. A better understanding of the mechanisms underlying this immune deficiency could lead to a better identification of patients at risk of infectious complications and to a better understanding of the vaccine efficacy deficit in CLL patients. Finally, earlier diagnosis and identification of patient profiles more likely to have bronchiectasis could allow for targeted and personalized therapeutic management and follow-up for each patient.