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RecruitingObservational

Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma Across the Military Healthcare System

NCT ID: NCT07652580Sponsor: Henry M. Jackson Foundation for the Advancement of Military MedicineLast updated: 2026-06-17

Summary

The goal of this observational cohort study is to learn how toxin and occupational exposures, germline genetic variation, and immune dysregulation relate to B-cell non-Hodgkin lymphoma among active-duty service members and other Military Health System beneficiaries. The main questions are whether specific exposures and germline variants are associated with B-cell NHL subtype, immune dysfunction, and clinical outcomes. Participants will complete exposure and medical-history surveys, provide biospecimens for immune and genomic testing, and may be followed annually for up to 3 years.

Detailed description

This prospective observational registry and biorepository study evaluates the relationship between occupational/environmental toxin exposures, immune dysregulation, and germline genetic susceptibility in active-duty service members (ADSMs) and other Military Health System (MHS) beneficiaries with B-cell non-Hodgkin lymphoma (NHL). Participants will be enrolled into one of three cohorts based on disease status and age, including individuals in remission, newly diagnosed adults, and treatment-naïve pediatric patients. The study will collect clinical, epidemiologic, immunologic, and genomic data longitudinally for up to 3 years. Participants will complete standardized surveys assessing demographics, military history, occupational/environmental exposures, medical history, and family history. Additional military exposure data may be obtained from the Department of Defense Individual Longitudinal Exposure Record (ILER). Clinical data abstracted from the electronic medical record will include lymphoma subtype, staging, pathology, treatment history, laboratory values, infectious complications, immune phenotyping, treatment response, recurrence, second malignancies, and survival outcomes. Biospecimens may include peripheral blood, skin fibroblasts, residual tumor tissue, bone marrow aspirate, and archived serum samples from the Department of Defense Serum Repository (DODSR). Germline and somatic genomic analyses will be performed using next-generation sequencing platforms, including whole genome sequencing. Immunologic analyses may include lymphocyte subsets, B-cell phenotyping, T-cell phenotyping, activation markers, cytokine profiling, and functional immune assays. The primary objectives are to characterize toxin exposures and immune dysregulation in B-cell NHL, identify germline pathogenic variants associated with lymphoma susceptibility, and establish a comprehensive longitudinal database and biospecimen repository for future translational research. Exploratory analyses will evaluate relationships among environmental exposures, genomic variants, immune phenotypes, lymphoma subtype, and clinical outcomes.

Arms & interventions

Outcome measures

Primary

  • Aim 1: Characterize occupational exposures and their impact on health outcomes and immune health of ADSMs and other MHS beneficiaries with B-cell NHL.

    1. Characterize and determine the prevalence of various toxin and occupational exposures in ADSMs and other MHS beneficiaries with B-cell NHL (Cohorts 1-3). 2. Characterize the B-cell NHL subtypes and health outcomes of NHL in ADSMs and other MHS beneficiaries (Cohorts 1-3). 3. Characterize immune dysregulation in ADSMs and other MHS beneficiaries with B-cell NHL. Immune dysregulation could be characterized by humoral vs cellular defects as well as innate vs adaptive defects among others (Cohorts 2-3).

    Time frame: 3 years

  • Aim 2: Identify and interpret germline variants in ADSMs and other MHS beneficiaries with B-cell NHL.

    1\. Determine the relative frequency of germline pathogenic/likely pathogenic variants in MHS beneficiaries with B-cell NHL (Cohorts 1-3).

    Time frame: 3 years

  • Aim 3: Create a comprehensive database and biorepository of ADSMs and other MHS beneficiaries with B-cell NHL.

    1. Create a database compiling clinical information, toxin exposure, military history (if applicable), and health outcomes (Cohorts 1-3). 2. Create a biorespository of peripheral blood (Cohorts 1-3).

    Time frame: 3 years

Secondary

  • Exploratory Endpoints

    Time frame: 3 years

Eligibility criteria

Sex: AllAge: 4 Years and olderHealthy volunteers: No
Inclusion Criteria: * Age 4 years old and older with a clinical diagnosis of B-cell NHL. * Must be willing to undergo phlebotomy and/or skin punch biopsy. * Must be willing to undergo whole genome sequencing, which includes return of primary and secondary findings. Exclusion Criteria: * Has any condition that, in the opinion of the Principal Investigator, contraindicates participation in this study. Examples of situation that may contraindicate participation include but are not limited to a) some cases of cerebral vascular accidents where an individual no longer has the capacity to make their own medical decisions and a conservator or responsible family member is not available and b) an individual has active suicidal ideation and is a danger to themselves at the time of enrollment. * Does not have access to health care and primary care clinician. * Actively undergoing induction treatment for NHL.

Study locations (3)

Uniformed Services University of the Health Sciences

Bethesda, Maryland, 20814

Active Not Recruiting

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814

Recruiting
Christin B Destefano · Contact
(301) 295-3190christin.destefano@usuhs.edu
Annika Hamann, RN, BSN, BS · Contact
(301) 295-4198annika.hamann.ctr@usuhs.edu
Jeremy Perkins, MD, FACP, COL, US Army (ret) · Principal Investigator

Naval Medical Center Portsmouth

Portsmouth, Virginia, 23708

Active Not Recruiting

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