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Using donated cells to treat acute Graft vs Host Disease (GvHD)

Jonathan in the Patient Services team discusses recent research into the use of cell therapies to treat Graft versus Host Disease (GvHD), which is a common side effect of stem cell transplant. He also looks at the implications this may have for patients whose symptoms have not responded to standard treatments.

 

Graft vs Host Disease (GvHD) is a very common side effect of having a stem cell transplant that can affect patients at different times in their recovery. It’s caused when the donor’s immune cells recognise the patient’s own cells as different and start to attack them.

GvHD can often be successfully managed using a combination of drugs and steroids that suppress the immune system. However, some patients experience GvHD which doesn’t respond to steroids. At the moment, further treatment options for these patients are limited, but research is currently underway to develop alternatives.

One of the most promising new areas of research uses ‘cell therapies’, where cells from a donor, or even the patient’s own cells, are given as treatment. These cells act as a ‘living drug’ because we take advantage of their natural function in the body. When they are put in the patient’s bloodstream, they either stop the problematic cells from working or remove them completely.

It’s even possible to alter the DNA of these cells before they are given to the patient, to make them more effective. This approach has already shown great promise by using modified T cells (a type of white blood cell), called CAR-T cells, to treat certain types of leukaemia. You can read more about this treatment in our blog on CAR-T cells.

 

How can cell therapy treat GvHD?

GvHD is caused when a donor’s T cells start to target the patient’s own cells, rather than destroy blood cancer cells or foreign invaders, like bacteria. If we can find a type of cell in the body that can control these T cells, they could be used as a cell therapy to treat GvHD.

Mesenchymal stromal cells (MSCs) are found in the bone marrow and have the potential to develop into many different cells types, but they don’t make blood cells. They help to control the immune system and inflammation following an infection or injury. They do this by stopping T cells from doing their normal job.

The idea of using MSCs to treat GvHD has been around for over a decade with very mixed results, but the treatment seems to work better in children. MSCs are only found in very small numbers in the blood, so they need to be collected and grown in the lab before they can be used as a treatment.

It’s thought that the lack of a standard method for doing this has caused some studies to be less successful than others. Scientists at the Frankfurt University Hospital in Germany have now developed a new way of growing these cells, after they have been isolated from donor blood samples. These cells have produced very promising and consistent results when given to patients with GvHD.

 

What did the study involve?

51 children and 18 adult patients with mainly high grade (III and IV) acute GvHD were given MSC therapy once a week for four weeks. Each of the patients had GvHD that didn’t react to steroids, and over 70% of them had also not responded to at least one other type of GvHD treatment.

After 28 days, the patients were assessed to see their response to the treatment. Then, over an average of eight months, patients attended follow-ups to see how well the treatment continued to work.

 

How successful was it?

Overall, this cell therapy was well-tolerated by the patients and worked as well in adults as it did in children. After 28 days, over 80% of patients showed an improvement in their GvHD symptoms. At the time of their last follow-up appointment, 61% of them showed no signs of acute GvHD and 25% showed signs of improvement.

Although some patients did die due to their illnesses, the study was able to show that following MSC therapy, the chance of surviving after six months was increased by just over 70%. This was compared to similar patients who did not have the therapy.

 

What does this mean for the future?

Although this was a relatively small study, it has shown that this new technique for collecting and growing MSCs can be used to develop cell therapies for treating GvHD.

The treatment gave patients relief from their symptoms, where they had very few options left because their GvHD had not reacted to standard treatments.

The cell therapy will now need to be tested on a larger scale before going into clinical trials, but at the moment it looks to be producing very promising results.

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