Longitudinal Prognosis of Lymphoproliferative Manifestations in Primary Immunodeficiencies

NCT07526714 | Not Yet Recruiting

• 1 other identifier: 2025PI074
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Primary Immune Deficiencies; Benign Lymphoproliferative Disorder

Keywords

Primary Immunodeficiency; Inborn error of Immunity; Lymphoproliferation; Lymphadenopathy; Splenomegaly

Outcome Measures

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.

  12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation

Secondary Outcomes (3)

• Longitudinal Evolution of Systemic Lymphoproliferation

  12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation

• Longitudinal Evolution of Organ-Specific Involvement

  12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation

• Occurrence of major clinical events according to baseline patient characteristics

  12 months minimum to 10 years retrospective follow-up from first documented benign lymphoproliferative manifestation

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• 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
• Followed in one of the participating centers

You may not qualify if:

• 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

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Related Publications (5)

• Gu H, Shu Z, Chen Z, Deng M, Lu D, Wu R, Wang T, Mao H. Effectiveness of sirolimus for early on-set autoimmune cytopenias of autoimmune lymphoproliferative immunodeficiencies. Pediatr Allergy Immunol. 2025 Sep;36(9):e70186. doi: 10.1111/pai.70186.

  PMID: 40898594 BACKGROUND

• Taghizade N, Babayeva R, Kara A, Karakus IS, Catak MC, Bulutoglu A, Haskologlu ZS, Akay Haci I, Tunakan Dalgic C, Karabiber E, Bilgic Eltan S, Yorgun Altunbas M, Sefer AP, Sezer A, Kokcu Karadag SI, Arik E, Karali Z, Ozhan Kont A, Tuzer C, Karaman S, Mersin SS, Kasap N, Celik E, Kocacik Uygun DF, Aydemir S, Kiykim A, Aydogmus C, Ozek Yucel E, Celmeli F, Karatay E, Bozkurtlar E, Demir S, Metin A, Karaca NE, Kutukculer N, Aksu G, Guner SN, Keles S, Reisli I, Kendir Demirkol Y, Arikoglu T, Gulez N, Genel F, Kilic SS, Aytekin C, Keskin O, Yildiran A, Ozcan D, Altintas DU, Ardeniz FO, Dogu EF, Ikinciogullari KA, Karakoc-Aydiner E, Ozen A, Baris S. Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency. J Allergy Clin Immunol. 2023 Dec;152(6):1634-1645. doi: 10.1016/j.jaci.2023.08.004. Epub 2023 Aug 16.

  PMID: 37595759 BACKGROUND

• Rao VK, Webster S, Sediva A, Plebani A, Schuetz C, Shcherbina A, Conlon N, Coulter T, Dalm VA, Trizzino A, Zharankova Y, Kulm E, Korholz J, Lougaris V, Rodina Y, Radford K, Bradt J, Kucher K, Relan A, Holland SM, Lenardo MJ, Uzel G. A randomized, placebo-controlled phase 3 trial of the PI3Kdelta inhibitor leniolisib for activated PI3Kdelta syndrome. Blood. 2023 Mar 2;141(9):971-983. doi: 10.1182/blood.2022018546.

  PMID: 36399712 BACKGROUND

• Herber M, Mertz P, Dieudonne Y, Guffroy B, Jung S, Gies V, Korganow AS, Guffroy A. Primary immunodeficiencies and lymphoma: a systematic review of literature. Leuk Lymphoma. 2020 Feb;61(2):274-284. doi: 10.1080/10428194.2019.1672056. Epub 2019 Oct 3.

  PMID: 31580160 BACKGROUND

• Yakaboski E, Fuleihan RL, Sullivan KE, Cunningham-Rundles C, Feuille E. Lymphoproliferative Disease in CVID: a Report of Types and Frequencies from a US Patient Registry. J Clin Immunol. 2020 Apr;40(3):524-530. doi: 10.1007/s10875-020-00769-8. Epub 2020 Mar 17.

  PMID: 32185577 BACKGROUND

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Lymphadenopathy; Splenomegaly

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Léa JACQUEL, MD

  CHRU Nancy Brabois

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Léa JACQUEL, MD, Clinical assistant

CONTACT

+33383153298; lea.jacquel@univ-lorraine.fr

JACQUEL

CONTACT

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 13, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP