Graft-versus-host disease (GVHD) is a serious condition that can occur after a person with a
hematopoietic malignancy, such as leukaemia, undergoes a stem cell transplant from a
donor. This disease mainly affects tissues that act as barriers in the body, like the skin and
intestines. Although steroids can help reduce the symptoms of GVHD, about one-third of
patients do not respond to this treatment and develop a more severe form called steroid-
refractory GVHD (SR-GVHD), which has poor outcomes. This situation highlights the urgent
need for new treatments.
We discovered that a protein called BCL2, which prevents cell death, might interfere with
how steroids work and is linked to higher risks after transplants. We believe that using a
drug called venetoclax, which inhibits BCL2, could improve the treatment of GVHD. Our goal
is to see if targeting BCL2 with venetoclax can alleviate the symptoms of GVHD and prevent
the development of SR-GVHD.
To explore this, we will conduct a clinical trial using venetoclax in GVHD patients. This trial is
innovative because it repurposes a cancer drug for a new use in GVHD treatment. We will
combine experimental and computational methods to study tissue samples from study
participants. Advanced technologies will help us understand how SR-GVHD develops and
how BCL2 inhibition works at the cellular and molecular levels.
Our project is unique because it combines different scientific approaches and uses a cancer
drug in a new way to prevent GVHD from becoming treatment-resistant. We will move from
clinical observations back to laboratory studies to gain detailed insights into the disease
mechanisms.
The study is led by experts in transplant immunology and clinical research in stem-cell
transplantation. By integrating a clinical trial with deep knowledge of BCL2 biology and
cutting-edge technologies, we aim to advance precision medicine for treating this
devastating disease.