# Low Dose of IL‐2 Application for Graft‐Versus‐Host Disease Prophylaxis Following Haploidentical Stem Cell Transplantation

## TL;DR

Low-dose IL-2 treatment after stem cell transplants boosts immune cells and lowers chronic GVHD risk.

## Contribution

Demonstrates that early low-dose IL-2 promotes NK and Treg cell reconstitution, reducing chronic GVHD after haploidentical HSCT.

## Key findings

- Low-dose IL-2 treatment reduced chronic GVHD incidence and improved GVHD progression-free survival.
- IL-2 increased NK cell counts and activation markers like CD122, DNAM-1, and NKG2D.
- Treg cells and plasma cytokines (IFN-γ, TNF-α, IL-10) were elevated following IL-2 administration.

## Abstract

Graft‐versus‐host disease (GVHD) are still key obstacles of haploidentical transplantation. Interleukin‐2 (IL‐2) could promote natural killer (NK) cells and T‐regulatory cells (Tregs) cells expansion in vitro and in vivo. We explored whether low‐dose IL‐2 administration at an early stage could promote NK cells and Tregs reconstitution and reduce GVHD after haplo‐HSCT. This cohort trial included 10 recipients of accepting IL‐2 treatment and case‐pairing 30 recipients without IL‐2 treatment post haplo‐HSCT. In contrast to the control group, the 5‐year incidence of chronic GVHD (cGVHD) was lower (p = 0.018), and GVHD progression‐free survival (GPFS) was better (p = 0.025) in the IL‐2 group. Blood NK‐cells, Treg cells, conventional T cells (Tcon) cells, and the expression of CD62L+ on Tregs and Tcon cells reconstitution were increased post‐IL‐2 treatment. NKG2A expression on NK cells increased significantly post‐IL‐2 treatment. Meanwhile, IL‐2 administration shortly increased the plasma levels of IFN‐Ƴ, TNF‐a, IL‐10, and IL‐2 in subjects post haplo‐HSCT. Relative to the control group, low‐dose IL‐2 increased NK cell counts and the expression of CD122, DNAM‐1, and NKG2D on NK cells post transplantation. Administration of low‐dose IL‐2 after haplo‐HSCT correlated with reduced cGVHD, which should be explored further with randomized trial.

Early low‐dose IL‐2 administration after haploidentical HSCT promotes the reconstitution of NK cells and regulatory T cells (Tregs), enhances their activation (CD122+, DNAM‐1+, NKG2D+, CD62L+), and increases plasma cytokines (IFN‐γ, TNF‐α, IL‐10, IL‐2). These immune modulations are associated with reduced chronic GVHD incidence and improved GVHD progression‐free survival.