Understanding the Role of Large Extracellular Vesicles in Lymphomas and Lymphoproliferative Disorders: the "Off the Beaten Track" Liquid Biopsy

Understanding the Role of Large Extracellular Vesicles in Lymphomas and Lymphoproliferative Disorders: the "Off the Beaten Track" Liquid Biopsy - A Prospective Monocentric in Vitro Study on Human Tissues

This study aims to investigate the role of extracellular vesicles as diagnosic and prognostic biomarkers in patients with lymphomas or lymphoproliferative disorders. In particular, circulating extracellular vesicles, thanks to their cargo of proteins, lipids, and nucleic acids, play a role in the communication between cells. Since it has been described that these vesicles are able to influence also immune cells, the study of their functions may lead to the discovery of new mechanisms underlying this type of diseases.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Diffuse Large B-Cell Lymphoma; Mycosis Fungoides; Chronic Lymphocytic Leukemia; T Cell Lymphoma; Hairy Cell Leukemia (HCL); Marginal Zone Lymphoma(MZL); Multiple Mieloma

Detailed Description

It is a 3-year monocentric in vitro study on human tissue. 50 patients with aggressive and indolent Non-Hodgkin Lymphomas (Diffuse Large B-Cell Lymphoma (DLBCL; Group A; n=10), Follicular Lymphoma (FL; Group B; n=10), Marginal Zone Lymphoma (MZL; Group C; n=10), Peripheral T-Cell Lymphoma (PTCL; Group D; n=10), Mycosis Fungoides (MF; Group E; n=10)), and patients with Chronic Lymphocytic Leukaemia (CLL; N=10; Group F; n=10), Hairy Cell Leukemia (HCL; Group G; n=10), and Multiple Myeloma (MM; N=10; Group H; n=10) will be enrolled over a period of 24 months. Follow-up: 12 months. Patients will be enrolled at the Complex Operative Unit of Haematology-IRCCS Azienda Ospedaliero-Universitaria di Bologna. The peripheral blood samples of patients (40 ml) will be collected only at diagnosis within normal clinical practice, outside of clinical study protocols, and following the treatment guidelines in use at the Centre. The analysis of the samples will be performed at the Unità Operativa Complessa di Ematologia-IRCCS Azienda Ospedaliero-Universitaria di Bologna in collaboration with the Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori' - IRST IRCCS and with the University of Perugia.

• Study Type: Observational
• Enrollment (Actual): 102

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients at diagnosis (Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Peripheral T-Cell Lymphoma, Mycosis Fungoides, Chronic Lymphocytic Leukemia, Hairy Cell Leukemia, Multiple Myeloma) will be enrolled over a 24 month period. Follow-up 1 year.

Sex/age matched healthy donors will be recruited for peripheral blood collection among volunteers of a no profit organization called Bologna AIL.

Description

Inclusion criteria for patients:

• Age ≥ 18 years.
• Patients with WHO 2017-defined diagnosis of indolent and aggressive Non-Hodgkin Lymphoma (specifically Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Peripheral T-Cell Lymphoma, Mycosis Fungoides) or Chronic Lymphocytic Leukemia or Hairy Cell Leukemia or Multiple Myeloma.
• Signed informed consent.

Exclusion criteria for patients:

- Concomitant secondary neoplasia.

Inclusion criteria for healthy donors:

• Age ≥ 18 years.
• Signed informed consent.

Exclusion criteria for healthy donors:

- Healthy donors with neoplasia.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular vesicle characterization	Comparison of concentration (particles/ml), phenotype, and cargo of extracellular vesicles from patients and healthy donors.	2 years
Validation of extracellular vesicles as biomarker	Correlation of extracellular vesicles' characterization results with biomarkers of disease aggressiveness and short-term response to standard therapy.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional effects of extracellular vesicles	Comparison of functional effects of extracellular vesicles from patients and healthy donors on selected immune cells. The isolated vesicles will be used to treat the immune cells (T cells, B cells, monocytes) to evaluate viability, phenotype, migration ability, and inflammatory cytokine production of the target cells.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular vesicles' cell of origin	Correlation of extracellular vesicles' phenotype with the corresponding cells of origin.	1 years

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Lucia Catani, PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2022
• Primary Completion (Actual): February 20, 2023
• Study Completion (Actual): November 17, 2024

Study Registration Dates

• First Submitted: December 30, 2024
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Infections; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Bacterial Infections and Mycoses; Leukemia, Lymphoid; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Leukemia; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoproliferative Disorders; Mycoses; Mycosis Fungoides; Leukemia, Hairy Cell
• Other Study ID Numbers: EVs-Lympho; RC-2024-2790168 (Other Grant/Funding Number: Italian Ministry of Health)

Drug and device information, study documents

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