Graft versus Host Disease (GvHD)

Graft versus Host Disease (GvHD)

Some people with blood cancer can be cured through stem cell transplants.

People are given very high doses of chemotherapy, and can also have whole body radiotherapy. Although this has a good chance of killing the cancer cells, it also kills the stem cells in the bone marrow, which give rise to the different types of blood cells. So after high dose treatment, stem cells or bone marrow from a matched donor (also called a donor or an allogenic transplant) are given into a vein to replace those that the cancer treatment has killed. Donor cells make their way to the bone marrow and go on to produce healthy blood cells.

Graft versus host disease (GVHD) is a complication that can happen after a stem cell transplant from another person. It is still hard to predict who will develop GvHD after a stem cell transplant, but around 20 to 80% of will develop some degree of GVHD.

GvHD occurs when the white blood cells in the donated stem cells or bone marrow attack the recipient’s cells in the body. Areas affected can vary, but are mainly skin, liver and gut. Symptoms of GvHD can also vary in severity, and include rash, jaundice and diarrhoea. People who have GvHD are usually given drugs that suppress the immune system, such as corticosteroids. 

Although GvHD can be severe and may even be life-threatening, there is also a beneficial aspect to this immune response, which is a necessary part of the curative effect of stem cell transplants. Donor cells are able to unleash an immune cascade that destroys any residual leukaemia cells very effectively. This is known as the graft versus tumour (GvT) or graft versus leukaemia effect (GvL). 

Our research is looking for new treatments for GvHD, and finding ways to optimise current treatments. And we want to find ways to boost the GvT/GvL effect, whilst dampening down GvHD.

Harnessing the immune system to fight leukaemia

When someone with blood cancer receives a stem cell transplant, often the immune system of the donor attacks blood cancer cells in the patient, preventing relapse. This is called the graft versus leukaemia (GvL) effect and is extremely beneficial.

But not all people have a strong GvL response, and our research wants to find out why. 

Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation

Lead researcher - Professor Paul Moss, University of Birmingham
Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation
Researchers led by Professor Moss want to investigate exactly how donor immune cells recognise and kill cancer cells. The aim of this research is to find new ways to increase the strength of GvL so that transplant treatments can be modified to the needs of individual people.

Improving the outlook of people living with Graft versus Host Disease

People who have chronic GvHD are usually given steroids, which damp down the immune system. But this course of treatment does not always work as people can become dependent on steroids, or their steroid treatment may no longer work. 

We are funding the AZTEC trial that wants to find out if using a chemotherapy called azacitidine helps people with GvHD. Azacitidine has a complicated mechanism of action, but in GvHD, it is thought to modulate the immune system, allowing the graft cells to establish themselves.

AZTEC trial

Chief investigator - Dr Ram Malladi, University of Birmingham
A Phase II study of the use of azacitidine for the treatment of patients with chronic graft versus host disease who have failed therapy with corticosteroids
People with GvHD are usually given steroids, but this course of treatment does not work for everyone. Researchers want to see if using a chemotherapy called azacitidine can help people with GvHD who are dependent on steroid treatment, or who are no longer responding to steroids. 

New treatments for people with Graft versus Host Disease

People who have GvHD are usually given drugs that suppress the immune system. But this course of treatment does not always work as people can become dependent on steroids, or their steroid treatment may no longer work. 

Cytokines are groups of proteins that act as cell signalling molecules, allowing cells to communicate with each other when generating immune responses. They perform a series of tasks, including instructing cells to move towards sites of inflammation and infection.

We are supporting research that is looking at cytokines as a new form of therapy for people with GvHD.

Optimising current Graft versus Host Disease treatments

During the last few years, Professor Francesco Dazzi and his team of researchers have developed a way to treat severe GvHD with mesenchymal stromal cells (MSC). MSCs are a rare population of stem cells found in the bone marrow, which can suppress immune responses that cause GvHD. 

The team have discovered that MSC injected into GvHD recipients are killed by host immune cells. The dying MSC are fundamental to produce the control of GvHD.

We are supporting further research that is looking to maximise the effects of MSC treatment.

Predicting who will respond to GvHD therapy

Lead researcher - Professor Francesco Dazzi, Kings College London
Molecular and phenotypic characterisation of a mechanistic biomarker predictive of clinical responses to mesenchymal stromal cells in graft-versus-host disease
Professor Dazzi and his team want to fully characterise the host killer cells in people with GvHD. Using this information, they will select the people who are more likely to respond to MSC therapy, and learn which drugs may interfere with the killer cells.

Preventing Graft versus Host Disease from happening in the first place

We are supporting trials that want to prevent GvHD from developing. 

A trial called ProT4 is looking at giving extra T cells after a “mini transplant” – a stem cell transplant from a sibling - for cancers of the blood or lymphatic system. People who have these transplants are given immunosuppressants to prevent GvHD, but this treatment also increases the risk of getting an infection.

A specific set of T-cells called CD4 cells can recognise and kill cancer cells, causing a beneficial graft versus lymphoma (GvL) effect. Researchers think that giving CD4 cells from the donor may help boost the immune system of people who receive transplants, reduce the risk of infection and prevent blood cancer returning in people undergoing mini transplants. 

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