# Comparison of Regulatory T-Cell Subpopulations in Antithymocytic Globulin Versus Post-Transplant Cyclophosphamide for Preventing Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation—A Retrospective Study

**Authors:** Bu-Yeon Heo, Jeong Suk Koh, Su-Young Choi, Thi Thuy Duong Pham, Sang-Woo Lee, Jung-Hyun Park, Yunseon Jang, Myung-Won Lee, Seul-Bi Lee, Wonhyoung Seo, Deog-Yeon Jo, Jaeyul Kwon, Ik-Chan Song

PMC · DOI: 10.3390/ijms26062521 · International Journal of Molecular Sciences · 2025-03-11

## TL;DR

This study compares T-cell subpopulations in two GVHD prevention methods after stem cell transplants, finding differences in regulatory T-cells that may predict GVHD severity.

## Contribution

The study identifies effector Tregs as a potential biomarker for predicting acute GVHD severity in transplant patients.

## Key findings

- PTCy group had higher conventional CD25+FOXP3+Treg counts compared to the ATG group.
- Effector Tregs were significantly higher in the PTCy group and inversely correlated with acute GVHD severity.
- No significant differences in overall survival or relapse rates were observed between the two groups.

## Abstract

Antithymocytic globulin (ATG) and post-transplant cyclophosphamide (PTCy) are frequently used regimens for graft-versus-host disease (GVHD) prophylaxis. However, there is a lack of data about the difference in regulatory T-cell (Treg) subpopulations between these two regimens. Peripheral blood samples were collected on day +21 following allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and the Treg subpopulations were analyzed using flow cytometry. The Treg populations were categorized into three distinct subgroups: naïve, effector, and non-suppressive. And we compared overall survival (OS), the cumulative incidence of acute and chronic GVHD, and the relapse rate between the ATG and PTCy groups. We enrolled 45 patients (28 in ATG, 17 in PTCy) in total. In the ATG group, 16 and 12 patients underwent human leukocyte antigen (HLA) matched-sibling donor and unrelated donor HSCT, respectively. In the PTCy group, 12 patients underwent haplo-identical HSCT, and 5 patients underwent HLA-matched unrelated donor HSCT. The cumulative incidence of Grade 2–4 acute GVHD was 18.3% in the ATG group compared to 38.1% in the PTCy group (p = 0.13), while severe chronic GVHD occurred in 19.4% of ATG patients and 41.7% of PTCy patients (p = 0.343). And OS and the relapse rate were not statistically different between the two groups. The conventional CD25+FOXP3+Treg count of CD4 + T cells was higher in the PTCy group than in the ATG group (p = 0.0020). The effector Treg subset was significantly higher in the PTCy group than in the ATG group (p = 0.0412). And the effector Treg cell count had an inverse correlation with the severity of acute GVHD (p = 0.0007). Effector Tregs may be used as a biomarker to predict the severity of acute GVHD after allo-HSCT.

## Linked entities

- **Proteins:** FOXP3 (forkhead box P3)
- **Chemicals:** cyclophosphamide (PubChem CID 2907)
- **Diseases:** graft-versus-host disease (MONDO:0013730), acute GVHD (MONDO:0020546), chronic GVHD (MONDO:0020547)

## Full-text entities

- **Genes:** CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}
- **Diseases:** GVHD (MESH:D006086)
- **Chemicals:** Cyclophosphamide (MESH:D003520), ATG (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11941908/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC11941908/full.md

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Source: https://tomesphere.com/paper/PMC11941908