Low dose of IL-2 application for graft-versus-host disease prophylaxis following haploidentical stem cell transplantation

Abstract

Abstract Graft-versus-host disease (GVHD) are still major obstacles of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Natural killer (NK) and T-regulatory cells (Tregs) could regulate alloreactive T cells function to prevent GVHD occurrence. Interleukin-2 (IL-2) could promote NK and Treg cells expansion in vivo and in vitro. We tested whether administering low-dose IL-2 at 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 recipient without IL-2 treatment post haplo-HSCT. Compared to the control group, the 5 years incidence of chronic GVHD was lower (P=0.018) and GVHD progression-free survival (GPFS) was higher (P=0.025) in the IL-2 arm. Incidence of acute GVHD, CMV viremia, EBV viremia and relapse were comparable between two groups. Blood NK-cells, Treg cells, conventional T cells (Tcon) cells, as well as the expression of CD62L+ on Tregs and Tcon cells reconstitution were increased post IL2 treatment. The expression of NKG2A expression on NK cells were significantly increased post IL2 treatment. Meanwhile, IL2 administration shortly increased the plasm levels of IFN-Ƴ, TNF-a, IL-10 as well as IL2 in subjects post haplo-HSCT. NK-cell cytotoxicity against K562 cells were comparable before and post IL2 treatment. Compared to the control group, low dose IL-2 increased the absolute numbers of NK cells as well as the expression of CD122, DNAM-1, NKG2D on NK cells post transplantation. Low-dose IL-2 post haplo-HSCT period was associated with a lower chronic GVHD, which should be explored further with randomized trial.