Treating pulmonary chronic graft-versus-host disease in adults

Who is this document for and what is it about?

This document explains the recommendations in the European Respiratory Society (ERS) and European Society for Blood and Marrow Transplantation (EBMT) clinical guidelines for pulmonary chronic graft-versus-host disease (cGvHD, also called lung cGvHD) in adults. It focuses on a form of lung cGvHD known as bronchiolitis obliterans syndrome (BOS). It is for people living with BOS in cGvHD, or their family or carers. This guideline does not cover children with the condition, or other types of cGvHD, such as acute GvHD. It also did not include people who develop the condition after lung transplantation.

What are clinical guidelines?

Clinical guidelines are produced after a scientific process used to gather the latest evidence on a condition or symptom. Guidelines also consider the opinions of experts and the priorities of patients and carers who have experience of a condition. Clinical guidelines are written for healthcare professionals. They use them as a best practice document on how to diagnose, manage and treat a condition.

What does this document include?

This document summarises the key points from the clinical guideline on lung cGvHD. It explains them in a way that is easier to understand for people who do not work in a medical field. It will include recommendations for how BOS should be treated.

By providing this information in an accessible way, this document aims to help people with lung cGvHD understand more about the care they should receive. This can help them to feel informed when making decisions about their treatment options.

There is currently no standard approach to managing this condition. This guideline aims to provide suggestions for a treatment plan, based on the latest available evidence and expert opinion. The recommendations from this guideline are classed as “conditional” because there is a lack of evidence on the topic. This means that healthcare professionals may suggest different treatment options in discussion with individuals.

Conditional recommendations from the full guideline are shown with this icon.

Graft-versus-host disease is a complication that can occur after allogeneic haematopoietic stem cell transplantation.

Allogeneic haematopoietic stem cell transplantation is a treatment option for a range of conditions affecting the blood. It involves the transfer of cells from one person to another. This type of stem cell transplant involves the transfer of cells that are able to make new blood cells in the recipient’s body. It can be used to treat a range of conditions including anaemia and blood cancers such as leukaemia, lymphoma and myeloma.

It can affect any organ. In this disease, transplanted cells (the graft) recognise the patient’s body (the host) as ‘foreign’ and attack the patient’s organs such as the skin, stomach, liver and lungs, leading to organ damage. The disease may occur soon after stem cell transplantation (acute) or develop later (chronic), in which case more organs can be affected. This guideline looks at chronic GvHD (cGvHD) that often occurs later.

The guideline focuses on cGvHD affecting the lungs. It focuses on a form of lung cGvHD known as bronchiolitis obliterans syndrome (BOS).

BOS can occur after stem cell transplantation but also after lung transplantation. It is a form of the body rejecting the transplant. It is caused by swelling (inflammation) and damage (scarring) of the airways. This causes the airways to narrow, leading to shortness of breath. It can also reduce a person’s ability to exercise or carry out day-to-day activities.

The narrowing of the airways may worsen over time, eventually leading to a person’s lungs failing. This can mean that a person needs to receive oxygen throughout the day, or in the worst case, it can cause death. About 5-14% of people who receive a stem cell transplant develop BOS within five years of the transplant procedure, although experts believe this is an underestimation.

Immediately after stem cell transplantation, medication, known as immunosuppressants, are given to help stop the body rejecting the new cells. These are usually gradually reduced and eventually stopped, to prevent side effects such as infection. In case of short-term or long-term GvHD, these immunosuppressants are started again. This guideline looked at what other medication could be used alongside the immunosuppressant treatments.

Medication

Inhaled corticosteroids and bronchodilators

Corticosteroids are drugs that reduce swelling (inflammation). Bronchodilators work by relaxing the muscles in the airways to make breathing easier. Both corticosteroids and bronchodilators are usually taken as a spray or powder that you breathe in (inhale) using an inhaler device. Corticosteroids are often given together in a combined inhaler with bronchodilators, to make them more effective. Both these medications are commonly used to treat lung conditions, such as asthma or chronic obstructive pulmonary disease (COPD).

Inhaled corticosteroids with or without bronchodilators can be considered to treat BOS in lung cGvHD in adults. It is important to select the best device to deliver the medication for each individual. Training can also be given on using inhalers to make sure the medication is taken properly.

For more information on how to use an inhaler properly, Asthma + Lung UK have a selection of videos you can watch.

Fluticasone, azithromycin and montelukast (FAM therapy)

Fluticasone, azithromycin and montelukast are three separate medications. Fluticasone is an inhaled corticosteroid. Azithromycin and montelukast are tablets that reduce swelling (inflammation). They can be used together in different combinations to treat BOS. If the medications are used together, it is known as FAM therapy.

Fluticasone, azithromycin and/or montelukast can be considered to treat BOS in lung cGvHD in adults. People at high risk of developing cancer should be careful taking azithromycin. Healthcare professionals should discuss the risks with these patients.

Medications commonly used for cancer and graft-versus-host disease

Imatinib is a medication used to treat cancer and GvHD. It is a targeted therapy, which means it works by finding and attacking cancerous cells. In cGvHD, it works by stopping the transplant cells (graft) from attacking the recipient’s (host) immune system.

There is no substantial benefit of imatinib to treat BOS in lung cGvHD in adults over conventional immunosuppressant treatments. Healthcare professionals should look at what other organs are affected by cGvHD, as imatinib can improve or worsen other cGvHD symptoms. Imatinib might be an option in patients with BOS and relapse of some cancer types (chronic myeloid leukaemia).

Ibrutinib is another targeted therapy used to treat cancer and GvHD. It works by blocking the growth of some cancers. In cGvHD, it works by stopping the transplant cells (graft) from attacking the recipient’s (host) immune system.

In general, ibrutinib should not be considered to treat BOS in lung cGvHD in adults. This is because ibrutinib is not very effective and can give many side effects, although it could work in a select group of people where other treatment options are not available.

Ruxolitinib is a targeted therapy used for cancer and GvHD. It is used when the body makes too many blood cells or when there is scarring of the bone marrow. In cGvHD, it works by stopping the transplant cells (graft) from attacking the recipient’s (host) immune system.

There is currently not enough evidence to suggest the benefit of ruxolitinib to treat BOS in lung cGvHD in adults over conventional immunosuppressant treatments. Healthcare professionals should use it carefully, particularly for people who have a history of repeated infections or conditions affecting the blood cells.

Medication designed to treat chronic graft-versus-host disease

Belumosudil is a type of targeted therapy that aims to treat cGvHD. The medicine works by treating the inflammation that occurs in graft-versus-host disease and leads to organ damage. This treatment was approved for patients in the USA in 2021 but is not yet approved in Europe at the time of writing.

There is currently not enough evidence to suggest the benefit of belumosudil to treat BOS in lung cGvHD in adults over conventional immunosuppressant treatments.

Extracorporeal photopheresis

Extracorporeal photopheresis is a non-surgical procedure to treat cGvHD. The treatment targets lymphocytes, a type of white blood cell that is part of the immune system and is responsible for transplant rejection. During the procedure, the patient’s blood passes through a machine to separate the white blood cells from the rest of the blood. The white blood cells are combined with a drug, then exposed to ultraviolet light to ‘activate’ the drug and finally transferred back into the patient.

The extracorporeal photopheresis procedure is often done over two days and repeated every couple of weeks (often less frequent after a few weeks).

Read about Sam’s experience of ECP treatment

Extracorporeal photopheresis can be considered to treat BOS in lung cGvHD in adults. It is a highly specialist treatment and only certain hospitals have the equipment and expertise needed to perform the procedure.

Lung transplantation

Lung transplantation is an operation to remove and replace a diseased lung with a healthy lung from a donor. It can be a treatment option for people living with cGvHD.

In a select group of adults who are at the end stages of BOS in lung cGvHD, lung transplantation can be considered as a treatment option. There needs to be specific criteria produced outlining who this treatment option would be best for.

Lung function tests

Lung function tests are used to measure how well the lungs are working. They can help to diagnose and monitor a range of lung conditions.

A commonly used lung function test to monitor cGvHD is spirometry. Spirometry is performed by deeply inhaling and forcefully breathing out into a device called a spirometer. The test measures the amount of air in the lungs and how fast a person can breathe out. It can help to indicate whether a person’s airways are narrowed, which can be a sign of BOS, and to monitor the effect of treatment.

Other lung function tests include a lung volume test and a gas transfer test.

Spirometry tests every three months should be considered for BOS in lung cGvHD.

A combination of all lung function tests can be considered for monitoring. It is suggested that they are carried out at the time BOS is diagnosed, every year after this and also when the disease progresses.

CT scans

A chest CT scan uses X-rays and a computer to create detailed images of the inside of the lungs. CT scans can be used to detect diseases such as infection, rejection or tumours.

It is suggested that high-resolution chest CT scans are carried out at the time of diagnosing BOS, and if there is a change in symptoms moving forwards.

There are other measures that could help people living with BOS in lung cGvHD. These include prevention steps, such as vaccinations, quitting smoking and pulmonary rehabilitation.

A range of other therapies can be considered to help people living with BOS in lung cGvHD:

• Flu vaccinations taken each year, according to existing recommendations for stem cell transplant recipients.
• Pneumococcal vaccination, which protects against pneumonia, according to existing recommendations for people living with cGvHD.
• COVID-19 vaccination with repeated booster vaccinations, according to local policies and existing recommendations for stem cell transplant recipients.
• Medication, known as antimicrobial prophylaxis, to lower the risk of certain infections, according to existing advice for people living with cGvHD.
• Immunoglobin therapy, which can help people with weakened immune systems to fight off infections. This should be offered according to existing advice for people living with cGvHD.
• Exercise and activity, including formal pulmonary rehabilitation programmes, for people with reduced levels of exercise.
• Long-term oxygen therapy for people who experience extreme breathlessness, according to existing recommendations for patients with chronic obstructive pulmonary disease.

Matthew Rutter has lived experience of pulmonary chronic graft-versus-host disease. In the video below, which helps explain the guidelines to professionals, he shares his story of the condition.

If you have experience of a lung condition, you can share your story with us to support other people with similar experiences.

This guideline was produced by the European Respiratory Society, the European Society for Blood and Marrow Transplantation (EBMT) and the European Lung Foundation. You can find out more about these organisations and access the full professional guideline using the links below:

Full clinical guideline – published in the European Respiratory Journal in March 2024.

About ERS

The European Respiratory Society (ERS) is an international organisation that brings together physicians, healthcare professionals, scientists and other experts working in respiratory medicine. It is one of the leading medical organisations in the respiratory field, with a growing membership representing over 140 countries. The ERS mission is to promote lung health in order to alleviate suffering from disease and drive standards for respiratory medicine globally. Science, education and advocacy are at the core of everything it does. ERS is involved in promoting scientific research and providing access to high-quality educational resources. It also plays a key role in advocacy – raising awareness of lung disease amongst the public and politicians.

About EBMT

The European Society for Blood and Marrow Transplantation (EBMT) is a non-profit medical and scientific organisation established in 1974 which hosts a unique patient registry providing a pool of data to perform studies and assess new trends. They aim to be the connection between patients, researchers and other stakeholders to anticipate the future of cellular and stem cell-based therapies. Their community of healthcare professionals is focused on innovation, research and the advancement of these fields to save and improve the lives of patients with blood-related disorders.

About ELF

The European Lung Foundation (ELF) was founded by ERS to bring together patients and the public with professionals. ELF produces public versions of ERS guidelines to summarise the recommendations made to healthcare professionals in Europe, in a simple format for all to understand. These documents do not contain detailed information on each condition and should be used in conjunction with other patient information and discussions with your doctor. More information on lung conditions can be found on the ELF website.