Longitudinal Prognosis of Lymphoproliferative Manifestations in Primary Immunodeficiencies
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorCentral Hospital, Nancy, France
About this trial
Primary immunodeficiencies (PIDs) are a heterogeneous group of inborn errors of immunity characterized not only by increased susceptibility to infections but also by immune dysregulation. Among immune dysregulation manifestations, lymphoproliferative disorders represent a frequent and clinically challenging complication. These manifestations may involve secondary lymphoid organs (lymphadenopathy, splenomegaly) as well as extranodal organs such as lungs, liver, and gastrointestinal tract, often with lymphocytic and/or granulomatous infiltration. In some patients, lymphoproliferation may progress to lymphoma or other malignancies.
Despite increasing knowledge about specific genetic subtypes of PIDs and the development of targeted therapies (e.g., PI3Kδ inhibitors, CTLA4 pathway modulation, mTOR inhibitors), the natural history and long-term prognosis of lymphoproliferative manifestations across unselected PID populations remain poorly defined. Most available studies focus on selected molecular subgroups or treatment responses, while real-world longitudinal data on broader PID cohorts are lacking.
The PID-LP study is a multicenter retrospective longitudinal study conducted in three tertiary care centers in France. It aims to describe the initial characteristics and long-term outcomes of patients with PIDs who develop lymphoproliferative manifestations.
The primary objective is to evaluate the occurrence of major clinical events during follow-up, defined as death (all causes), occurrence of lymphoma or other malignancy, or clinically significant organ dysfunction attributable to lymphoproliferation.
Secondary objectives are to describe the longitudinal evolution of systemic lymphoproliferation (lymph node size, splenomegaly), the progression of organ involvement (pulmonary, hepatic, gastrointestinal), and to identify clinical, biological, genetic, radiological, and therapeutic factors at diagnosis that may predict major complications.
Approximately 60 pediatric and adult patients diagnosed between 2014 and 2025 and followed for at least 12 months after diagnosis of lymphoproliferation will be included. Data will be retrospectively collected from medical records.
This study is expected to improve the understanding of prognosis and disease trajectories in PID-associated lymphoproliferation, inform follow-up strategies, and generate hypotheses for future prospective interventional studies.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Diagnosis of primary immunodeficiency (inborn error of immunity) according to ESID criteria
Presence of systemic lymphoproliferative manifestations (e.g., persistent lymphadenopathy, splenomegaly, lymphoma) and/or organ involvement attributable to lymphocytic or granulomatous infiltration
Diagnosis of lymphoproliferative manifestation between January 1, 2014 and December 31, 2025
Minimum follow-up of 12 months after diagnosis of lymphoproliferative manifestation
Disqualifiers
Secondary immunodeficiency (e.g., HIV infection, immunosuppression due to chemotherapy, solid organ transplantation, or other acquired causes)
Isolated reactive lymphadenopathy clearly attributable to acute infection without evidence of persistent lymphoproliferation
Insufficient clinical data available in medical records to assess baseline characteristics or outcomes
Follow-up duration < 12 months after diagnosis of lymphoproliferative manifestation
Trial population
Adult and pediatric patients diagnosed with a primary immunodeficiency (PID) who exhibit lymphoproliferation, with or without associated autoimmune manifestations. Patients are followed longitudinally to assess clinical outcomes, comorbidities, treatment responses, and correlation with cellular phenotypes. Exclusion criteria include secondary immunodeficiencies, active malignancies unrelated to PID, or inability to provide informed consent.
Trial design
Design model
Cohort
Time perspective
Retrospective
Treatments tested in this trial
Not listed
Trial groups
No trial groups listed
Trial outcomes
Primary outcomes
1
Occurrence of Major Clinical Events
The primary outcome is the occurrence of at least one major clinical event during follow-up, defined as any of the following: * All-cause mortality; * Diagnosis of lymphoma or other malignancy; * Clinically significant organ dysfunction attributable to lymphoproliferative involvement (including pulmonary, hepatic, gastrointestinal, or splenic complications), as documented by clinical, biological, and/or radiological criteria and requiring specific medical or surgical management. Each event will be recorded as a time-to-event variable from the date of lymphoproliferation diagnosis.
Time frame
12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestationSecondary outcomes
1
Longitudinal Evolution of Systemic Lymphoproliferation
This secondary outcome assesses the longitudinal evolution of systemic lymphoproliferative manifestations over time. It includes changes in lymphadenopathy and splenomegaly between baseline (date of lymphoproliferation diagnosis) and last available follow-up. Systemic lymphoproliferation will be evaluated through: * Presence or absence of lymphadenopathy; * Maximum lymph node diameter on clinical examination or imaging; * Presence and degree of splenomegaly (clinical assessment and/or imaging measurements); * Need for invasive diagnostic or therapeutic procedures related to lymphoproliferation (e.g., lymph node biopsy, splenectomy). Evolution will be categorized as regression, stability, or progression based on predefined clinical and radiological criteria.
Time frame
12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation2
Longitudinal Evolution of Organ-Specific Involvement
This secondary outcome evaluates the evolution of organ-specific involvement attributable to lymphoproliferative or granulomatous infiltration in patients with primary immunodeficiency. Organ involvement includes pulmonary, hepatic, and gastrointestinal manifestations documented at baseline and during follow-up. * Pulmonary involvement is assessed by clinical symptoms, pulmonary function tests (FVC, FEV1, DLCO when available), and imaging findings. * Hepatic involvement is evaluated using clinical data, liver function tests, imaging, and evidence of fibrosis or portal hypertension. * Gastrointestinal involvement includes documented inflammatory or granulomatous lesions, malabsorption, or need for nutritional support. Evolution is categorized as regression, stability, or progression based on predefined criteria.
Time frame
12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation3
Occurrence of major clinical events according to baseline patient characteristics
Proportion of patients experiencing at least one major clinical event during follow-up, defined as death, lymphoma, or clinically significant organ dysfunction. This outcome will be analyzed according to baseline demographic, clinical, immunological, genetic, radiological, and treatment characteristics, including age, sex, and type of inborn error of immunity.
Time frame
12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestationLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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