Tissue Immune Landscape of Graft Versus Host Disease After Allogeneic Stem Cell Transplantation (TIL-GVHD) (TIL-GVHD)

Graft versus Host Disease (GVHD) is frequent after allogeneic stem cell transplantation (alloSCT). GVHD occurs following 2 patterns : acute GVHD (aGVHD) or chronic GVHD (cGVHD). The latter occurs in nearly 50% of patients and its pathogenesis remains poorly understood. Previous translational studies have delineated biological immune dysregulation involved in cGVHD and facilitated the development of new drug and therapeutic strategies. New aspects of T and B cells collaboration in the context of cGVHD using blood description of a key player called TFH, classicaly involved in germinal center reaction, were previously uncovered (Forcade et al, Blood 2016). Previous studies in the context of auto-immune inflammation (lupus nephritis) or organ transplant rejection, suggested that target tissue could contain accessory lymphoid structures (TLS). The description of such structures in cGVHD target tissue would give the opportunity to directly analyze immune key player involved the pathogenesis of cGVHD.

Study Overview

• Status: Recruiting
• Conditions: Chronic Graft Versus Host Disease
• Intervention / Treatment: Biological: Additional blood sample; Biological: cGVHD target tissue biopsy

Detailed Description

Context :

Chronic Graft versus Host Disease (cGVHD) represents the main cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (alloSCT), occurring in 30 and 60%. Translational studies showed that different alloreactive T cell subsets were involved and associated with cGVHD, and regulatory subsets were deficient. Several homeostatic abnormalities of B cell subsets were also shown, which, in the context of high BAFF level, contributed to autoreactive B cell clone emergence.

In alloSCT patients, we observed (Forcade et al, Blood 2016) in the blood, a T cell subset called TFH, with B cell help capacity, similar to germinal center reaction. During cGVHD, blood TFH were highly activated, skewed toward a Th1/Th17 profile, and presented enhanced capacity to provide " help " to B cells, promoting auto-/allo-antibody production in the context of cGVHD. This was associated with increased level of CXCL13 in such patients, suggesting homing of this subset to lymphoid tissues.

Liarski et al (Sci Trans Med 2014) showed that TFH were observed in inflamed tissue sample from patients with lupus, and demonstrated close interaction with B cells, mimicking germinal center structures, such as tertiary lymphoid organs.

Preliminary data, on cGVHD tissue target, showed a CD4+ T cell infiltrate, of which some expressed CXCR5, ICOS, PD1 in single staining.

Hypothesis : cGVHD target tissue contains tertiary lymphoid structures.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edouard FORCADE; Phone Number: +33557656511; Email: edouard.forcade@chu-bordeaux.fr

Study Locations

• France
  • Pessac, France
    • Recruiting
    • CHU de Bordeaux, Service d'Hématologie Clinique et Thérapie Cellulaire
    • Contact: Edouard FORCADE; Email: edouard.forcade@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient > 18 yo ;
• Having undergone an allogeneic stem cell tranplant ;
• 2 groups of patients will be eligible

• showing evidence of primary cGVHD or occuring after Donor Lymphocyte Infusion

  • in the case of first occurrence of cGVHD, in the absence of any new systemic therapy ;
  • in the case of recurrent cGVHD, steroid dose has to be below 15mg/day of Prednisone ;
• Having read, understood and signed an informed consent of the study;
• With social security affiliation;

Exclusion Criteria:

• Patient below 18 yo or unable to give consent ;
• Systemic therapy using steroids over 15mg/d of Prednisone ; and/or the use of other systemic agent introduced in the last month ;
• Haemorrhagic risk of biopsy anticipated ;
• Absence of patient agreement for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with cGVHD	Biological: Additional blood sample; The procedure will consist of an additional blood sample for 3 ETDA tubes collection (NGS analysis) and citrate tube collection (NETose analysis); Biological: cGVHD target tissue biopsy; For chronic GVH patients only, cGVHD target tissue biopsy
Other: Patients without cGVHD	Biological: Additional blood sample; The procedure will consist of an additional blood sample for 3 ETDA tubes collection (NGS analysis) and citrate tube collection (NETose analysis)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To describe immune landscape in chronic GVHDtarget tissuesubsets, especially TFH, within cGVHD tissue target, using flow cytometry and histology	Flow cytometry and multiplex tissue imaging. GVHD evaluation using NIH score	At inclusion visit

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Biopsy; Tertiary lymphoid structures; Chronic GVHD; TFH
• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease
• Other Study ID Numbers: CHUBX 2021/15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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