Phase I/II Trials of Donor Regulatory T Cells for the Treatment of Steroid-Refractory Chronic Graft versus Host Disease

Chronic Graft versus Host Disease (cGVHD) remains a major hurdle to the success of hematopoietic stem cell transplantation (HSCT), directly impacting patient morbidity and mortality. Impaired Treg recovery in patients with cGVHD has led to clinical studies aiming to increase peripheral Treg numbers. We performed Phase I dose escalation clinical trials, testing the feasibility and safety of using freshly isolated donor-derived Treg infusions in steroid-refractory/dependent cGVHD. The Phase I was extended to a preliminary Phase II trial, resulting in a total of 33 treated patients. We report that Treg purification from donor leukapheresis using CliniMACS were feasible and that Treg infusions were safe. Importantly, Treg infusions resulted in improved symptoms, particularly at higher Treg doses. Global responses were observed in 71% of patients, and 52% of patients had at least a 2-point improvement in the cGVHD severity scale. Furthermore, improvement in cGVHD symptoms resulted in reductions in corticosteroids, ruxolitinib and mycophenolate (MMF) in 58%, 83% and 33% of patients, respectively, while calcineurin inhibitors were discontinued in 75% of patients. Exploratory analyses revealed the detection of infused Treg clonotypes up to 12 months post-infusion and suggest increased Treg numbers in circulation. We observed increases in serum levels of IL-7, IFN-g, and decreases in sCD13 and ST2 over time, which were not statistically significant following adjustment for multiple comparisons. Although these studies were not powered to assess efficacy, they suggest potential therapeutic benefits of donor-derived Treg in cGVHD treatment and highlight the need for larger Phase II clinical trials. NCT02385019 NCT03683498 (clinicaltrials.gov).

Authors

Institutions

Publication Details

Journal
Blood Advances
Published
2026-02-04
DOI
https://doi.org/10.1182/bloodadvances.2025017996
Primary Topic
Hematopoietic Stem Cell Transplantation
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Phase I/II Trials of Donor Regulatory T Cells for the Treatment of Steroid-Refractory Chronic Graft versus Host Disease

Nuno L. Barbosa‐Morais, Rosa Branca Ferreira, Paulo N. G. Pereira, Mario Arpinati et al.
Blood Advances
Hematopoietic Stem Cell Transplantation
article

Phase I/II Trials of Donor Regulatory T Cells for the Treatment of Steroid-Refractory Chronic Graft versus Host Disease

Nuno L. Barbosa‐Morais, Rosa Branca Ferreira, Paulo N. G. Pereira, Mario Arpinati, Kukatharmini Tharmaratnam, Petra Hoffmann, Clara García-Calderón, Paulo A. Palmela, Raúl Moreno, Ana Quintas, Hans-Jörg Warnatz, Rodríguez-Gil Alfonso, M Edinger, Ana Garção, Carlos Pinho Vaz, John Koreth, Susana Roncón, Ana C. Alho, JEROME RITZ, Ana Pais, Frédéric Baron, Laura Mendes, Marie-Laure Yaspo, António Maria Campos, Fernanda Lourenço, Estefanía García-Guerrero, Carlos Martins, João F. Lacerda, Christopher Paul Cheyne, Rita I. Azevedo, Maria VD Soares, Inês A Cabral, Ana Cláudia Ribeiro, José Antonio Antonio Pérez-Simón, Virginia Escamilla Gómez, Clara Juncal, Hans Rudolf Lehrach, Laura Ward, Marta Garcia-Finana, Eduardo Lima da Silva Espada, Teresa Caballero-Velázquez, Luís Leite, Fernando Campilho, Anabela Rodrigues, Cecília maria franco Caldas
article en

Abstract

Chronic Graft versus Host Disease (cGVHD) remains a major hurdle to the success of hematopoietic stem cell transplantation (HSCT), directly impacting patient morbidity and mortality. Impaired Treg recovery in patients with cGVHD has led to clinical studies aiming to increase peripheral Treg numbers. We performed Phase I dose escalation clinical trials, testing the feasibility and safety of using freshly isolated donor-derived Treg infusions in steroid-refractory/dependent cGVHD. The Phase I was extended to a preliminary Phase II trial, resulting in a total of 33 treated patients. We report that Treg purification from donor leukapheresis using CliniMACS were feasible and that Treg infusions were safe. Importantly, Treg infusions resulted in improved symptoms, particularly at higher Treg doses. Global responses were observed in 71% of patients, and 52% of patients had at least a 2-point improvement in the cGVHD severity scale. Furthermore, improvement in cGVHD symptoms resulted in reductions in corticosteroids, ruxolitinib and mycophenolate (MMF) in 58%, 83% and 33% of patients, respectively, while calcineurin inhibitors were discontinued in 75% of patients. Exploratory analyses revealed the detection of infused Treg clonotypes up to 12 months post-infusion and suggest increased Treg numbers in circulation. We observed increases in serum levels of IL-7, IFN-g, and decreases in sCD13 and ST2 over time, which were not statistically significant following adjustment for multiple comparisons. Although these studies were not powered to assess efficacy, they suggest potential therapeutic benefits of donor-derived Treg in cGVHD treatment and highlight the need for larger Phase II clinical trials. NCT02385019 NCT03683498 (clinicaltrials.gov).

Blood Advances
Harvard University (US), University of Lisbon (PT), University of Liverpool (GB), University of Liège (BE), University of Potsdam (DE), University Hospital Regensburg (DE), Hospital de Egas Moniz (PT), IPO Porto (PT), Dana-Farber Cancer Institute (US), Instituto de Biomedicina de Sevilla (ES), Max Planck Institute for Molecular Genetics (DE), Hospital de Santa Maria (PT), Hospital Universitario Virgen del Rocío (ES), Leibniz Institute for Immunotherapy, Instituto Gulbenkian de Ciência (PT), Universidad de Sevilla (ES), Universidade Nova de Lisboa (PT), University of Bologna (IT)
Amgen, AstraZeneca, Sanofi, Gilead Sciences, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Incyte, European Commission, Swedish Orphan Biovitrum
Good health and well-being
Openalex Percentile: Top 64%
Hematopoietic Stem Cell Transplantation
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.