Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas

Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterised not only by an infectious diathesis, but by a wide variety of other clinical manifestations. Lymphoma is one of the most common malignancies in children and may be the first clinical manifestation of IEI, thereby 'hiding' the immune defect and delaying genetic/immunological diagnosis. Lymphomas, especially non-Hodgkin's lymphomas (NHL) are frequently associated with congenital defects of the immune system, in particular diffuse large B-cell lymphoma and Burkitt's lymphoma. Preliminary analyses conducted on 6 patients diagnosed with NHL allowed the identification of genetic variants in genes associated with IEI. In clinical practice, the diagnosis and choice of therapeutic treatment in patients with immunodeficiency-associated lymphoma are decisive and, due to the complex pathophysiology of the disease, it is not always possible to identify the boundary between benign and malignant proliferation. The identification of an undiagnosed immunodeficiency in patients with lymphoma will ensure the opportunity to apply targeted therapies, such as allogeneic haematopoietic stem cell transplantation, instead of standard clinical management based mainly on chemotherapy. The study aims to identify possible congenital defects of immunity, i.e. genetic disorders affecting the immune system, as responsible for the development of haematological malignancies. Through a multidisciplinary approach involving immunological analyses, genetic analyses and a thorough examination of clinical manifestations, we aim to characterise the immunological component underlying the development of paediatric lymphomas.

Study Overview

• Status: Recruiting
• Conditions: Immune Deficiency
• Intervention / Treatment: Other: Analysis of biological sample and clinical data

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eleonora Gambineri; Phone Number: 0555662624; Email: eleonora.gambineri@meyer.it

Study Locations

• Italy
  • Bologna, Italy
    • Active, not recruiting
    • AOU Malpighi IRCCS
  • Florence, Italy
    • Recruiting
    • Meyer Children's Hospital IRCCS
    • Contact: Eleonora Gambineri; Email: eleonora.gambineri@meyer.it
  • Pisa, Italy
    • Active, not recruiting
    • AOU Pisana
  • Roma, Italy
    • Active, not recruiting
    • Ospedale Pediatrico Bambin Gesù IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a clinical diagnosis of Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NEIL) with or without signs of immune dysregulation (lymphoproliferation, autoimmunity, hypogammaglobulinaemia, family history of immunodeficiency).
• Patients with previous HL or NEIL lymphoma who have developed, concomitantly with the tumour or subsequently, clinical manifestations mentioned above attributable to a congenital defect of immunity.

Exclusion Criteria:

• Patients with known genetic diseases, or who do not consent to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patient with Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NEIL)	Other: Analysis of biological sample and clinical data; Analysis of biological sample and clinical data

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To unravel inborn error of immunity behind Lymphoid neoplasm in children	Characterizing the role of the immune system in the pathogenesis of polyclonal and clonal lymphoproliferation. In particular, the main aim of our study will be the identification, by means of second-generation genetic analysis and functional validation studies of the identified variants, of congenital immune system defects in patients with lymphoid neoplasia	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of lymphoma-specific biomarkers	Investigating Cell-Free DNA for specific molecular alterations in lymphomas, in order to monitor the follow-up of patients affected by lymphoma and to identify early onset of clonality in patients with already diagnosed congenital defects of the immune system at risk of developing malignant lymphoproliferation.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Meyer Children's Hospital IRCCS
• Investigators: Principal Investigator: Eleonora Gambineri, Meyer Children's Hospital IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2023
• Primary Completion (Estimated): June 18, 2025
• Study Completion (Estimated): October 18, 2025

Study Registration Dates

• First Submitted: February 24, 2024
• First Submitted That Met QC Criteria: March 18, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: L-IEI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No