John Murray is Nurse Clinician in BMT at The Christie NHS Foundation Trust. He’s been working with patients post-transplant since qualifying as a nurse in 1991, and has a special interest in GvHD.
Here he talks us through what it means to live with GvHD, why it affects some people and not others, and how long it can last.
For more information, you can read Part 2 of John’s Q&A, Looking after yourself in the long-term, which includes his advice on dealing with GvHD, taking care of your health, and how current research could improve treatment.
GvHD is a complicated side effect of transplant. Could you explain what it is and why it happens?
John: After a transplant, your body is still your body; your hair is still your hair. Your teeth and kidneys and other organs, they’re all still you. Attached to the outside of the cells throughout your whole body are little cell markers that let your immune system know they belong to you. They’re the ‘self’.
But with a transplant, we clear out all of the bone marrow with conditioning therapy (chemotherapy with or without total body irradiation) and then transplant in new marrow – so you have a new immune system developing in your bone marrow space. These new donor cells are slightly different to yours. Their cell markers are slightly different, even when they’re fully matched with sophisticated equipment in the laboratory.
The donor’s cells recognise that the other cells in your body are different, and your body recognises the differences too. When you get a virus, your body recognises that it’s not ‘self’ – it’s not a part of you – and it tries to destroy it. It’s the same process after a transplant – the graft attacks the host because it thinks it doesn’t belong there. And that’s graft versus host disease.
Is there anything my team can do to prevent this from happening?
John: Yes! To stop this reaction, you’ll be given an immunosuppressive drug before you have your stem cell or bone marrow transplant. The drug used most often is ciclosporin.
The ciclosporin acts like a minder between the two sides (your own cells and the new donor cells) – it tells both of them to calm down, and it keeps the systems apart. Then, over a period of time, it allows them to tolerate each other. The ciclosporin dose will gradually be reduced, and if there aren’t any problems they’re usually stopped completely within three to six months.
GvHD can happen at any time after transplant, but it can often be when the ciclosporin is being reduced. The first sign could be that you have a rash, or an upset stomach with nausea, vomiting or diarrhoea, or it could affect your liver, causing signs of jaundice. You should report anything unusual to your team straight away so that they can assess whether you have GvHD and start treatment to control the symptoms.
Why do some people get GvHD while others don’t?
John: Well, there are a number of factors that can increase the risk of GvHD – for instance, it’s more common if your transplant is from an unrelated donor rather than a sibling. A mismatch in your donor tissue typing, having an older donor, having a female donor if you’re a male patient, having a female donor who’s had multiple pregnancies, having higher doses of peripheral blood stem cells, and having certain types of conditioning therapy can all make GvHD more likely.
Infections after a transplant can lead to GvHD, because they put the immune system on high alert. And if you need an infusion of lymphocytes (DLI) from your donor because you still have some of your own bone marrow – this is called mixed Chimerism – this will increase the risk of GvHD.
But sometimes, we just don’t know why one person will develop GvHD, and another person who’s had the same kind of treatment won’t – although there are lots of theories! [For more on the research being done to find the answers, see Part 2 of John’s Q & A ]
Why do some doctors say that a little bit of GvHD isn’t a bad thing?
John: Your body developed cancer because of one bad cell that multiplied, then took over. Your transplant gives you a new immune system from a healthy donor which looks for cancerous cells and destroys them, much like your body did in the past. A little GvHD enhances this ability, because it puts your immune system on high alert. Grade One or Grade Two GvHD means you’ll have a good immunity, and protection from relapse.
However, if you’re taking immunosuppressive drugs, such as steroids, that could lead to a higher risk of infection. So it’s a constant balancing act between the original blood disorder, the GvHD, and your medications. If you don’t have GvHD, it doesn’t mean you have a higher risk of relapse – it just means the balancing act is different.
Can GvHD happen at any time? How long after a transplant could it appear?
John: There are different types of GvHD that happen at different times. Acute GvHD appears within 100 days. It could clear up with first-line treatment, or it could change and develop over time and become a chronic form.
For example, you could have a rash on your skin. It’s itchy, and raised, and it spreads to different areas. It fades over time with steroids, but then it changes in nature and becomes a chronic condition. It could become scleroderma – firm and thickened skin, so quite a different thing.
Chronic GvHD is more likely if you’ve had acute GvHD, but it can just suddenly appear. If you’re going to get it, it normally happens within two years. How long it lasts depends on how bad it is and how well you respond to treatment, and it can sometimes eventually burn out. Chronic GvHD (cGvHD) is different from acute GvHD, in that it causes more serious changes, typically to the skin, lung, mucous membranes, gastrointestinal tract or musculoskeletal system.
And then there’s overlap GvHD, which has some features of chronic and acute GvHD at the same time - so it can be difficult to figure out what’s going on!
Finally, late onset GvHD looks like acute GvHD, but it starts after 100 days. For example, if you’ve had a boost of lymphocytes from your donor, when you come off your immunosuppressive drugs you might get GvHD a month or so later – more than 100 days after your transplant.
What does ‘burn out’ mean?
John: Sometimes GvHD just goes away – the two sides become tolerant of each other, and that’s the end of it.
However, even when the disease goes away, the symptoms can remain. So, for example, your skin could feel tight, which means your joints wouldn’t bend properly. So it can have an impact on your day-to-day life.
Which parts of the body does GvHD usually affect? Does that make a difference to how it’s treated?
John: It can affect anywhere. Blood goes everywhere, so the two systems of the graft and the host can meet anywhere in the body, at a cellular level and an immune level. The skin, gut and liver are the most common places to get acute GvHD – because they’re all large organs for your blood to reach – and the eyes and mouth are fairly common in cGvHD.
And depending on the area of the body, the GvHD will be treated in slightly different ways. If you’re on ciclosporin and you develop GvHD, steroids are usually the first line treatment. They take away the inflammation and calm things down. Then we can add other treatments in combination, depending on where your symptoms are.
But it’s difficult to know what will work for different people, as we don’t have enough really good research evidence – although this is improving with time. There’s research happening around the use of ECP (extracorporeal photopheresis, or light therapy) for treating skin, liver, mouth and lung GvHD, so we could see this being used more widely over the next few years.
We hope you found these answers useful.
For information and advice on living with GvHD and how you can take care of yourself, see Part 2 of John’s Q&A, Looking after yourself in the long-term
For more information about GvHD and life after transplant, you can download our free publication ‘The Seven Steps: the next steps’
If you’re a partner or family member read our page about supporting someone through a transplant.
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DISCLAIMER: At Anthony Nolan we take great care to provide up-to-date and accurate facts about stem cell transplant. We hope the information here will help you to look after yourself. Each transplant centre will do things differently, so this blog is just a general guide and isn’t intended to replace advice from your doctor and transplant team. Please speak to your transplant team for more details about your own situation as they will be able to give you personalised, specific advice.