Pulmonary Complications Post Haematopoietic Stem Cell Transplant

Introduction

In recent years, a variety of complex illnesses can be treated by haematopoietic stem cell transplantation (HSCT, also called bone marrow transplantation or stem cell transplantation). Lung complications occur in approximately 25% of paediatric HSCT recipients. Complications can be due to infections or non-infectious causes in different phases after transplantation. Chronic graft-versus-host diseases (cGVHD) of the lung is one of the late phase non-infectious complications developed from around 100 days to two years after allogenic HSCT. Lung cGVHD can be serious contributing to significant transplant-related morbidity and mortality.

Causes and Risk Factors

Due to the preparatory procedures for the transplant, the body’s immunity is weakened. In the early phase after transplantation, complications related to lung infections may be caused by bacteria, fungi, or viruses. In later phases after transplantation, pulmonary complications are more commonly caused by non-infection-related conditions.

Chronic GVHD is one of the complications after HSCT that can affect multiple body systems and organs like the skin, gut and lungs. In cGVHD, the donated bone marrow or peripheral blood stem cells view the recipient’s body as foreign and often attack multiple organs including the lungs, leading to serious lung injury. The damage causes fibrosis and progressive narrowing of small airways manifested as a condition called bronchiolitis obliterans syndrome (BOS). Some of the risk factors for lung cGVHD include non-related donor, history of acute GVHD, radiotherapy and certain drugs in chemotherapy. The following information mainly focuses on lung cGVHD.

Signs and Symptoms

In the early stage of lung cGVHD, patients can be asymptomatic or present with nonspecific symptoms such as dry cough and mild shortness of breath on exertion. When the disease progresses, patients may experience considerable breathing difficulty, decreased exercise tolerance, and persistent cough. Physical activities are limited and there may be a need to use oxygen. Death will eventually occur mainly in association with infectious complications in very severe cases. It is thus important to anticipate and diagnose the condition early to prevent irreversible lung injury.

Diagnosis

The most definitive way to diagnose lung cGVHD is by histopathological confirmation of lung biopsy which is rarely performed due to its invasive nature. Current recommendations for diagnosis are primarily based on abnormalities of lung function testing and high-resolution computed tomography (HRCT) lung scans. Other investigations are performed to exclude infections. These may include blood tests, nasal swabs, sputum cultures or bronchoscopy for bronchoalveolar lavage to collect samples from the lower respiratory tract for tests.

• Lung function tests: They are non-invasive tests performed in our respiratory medicine unit. Most children over 5 to 6 years old can perform the tests. Your child will be given instructions to perform a series of blowing tests with the lung function machine. The complete set of tests take around 60 to 120 minutes. These tests are performed before HSCT as baseline assessment and done regularly after transplantation in order to detect abnormalities early for any features of lung cGVHD.
• High-resolution CT scans (HRCT) of the lungs: Radiological imaging with CT scan of the lungs will be done if there are lung function abnormalities or clinical symptoms and signs suggestive of lung cGVHD. HRCT is helpful in determining the likelihood of an infectious versus non-infectious etiology or identifying characteristic findings associated with cGVHD.

Management

Treatment options for pulmonary cGVHD are considered based on the extent of lung involvement. The aim is to maintain the patients lung function as much as possible and prevent further decline.

Medical treatment

• With mild to moderate severity of lung disease, your child may be prescribed a triple combination medications to decrease inflammation of the airways, known as “FAM” therapy, which includes Fluticasone, Azithromycin, and Montelukast.
• Inhaled Fluticasone is an inhaled corticosteroid commonly used in asthma, usually taken twice a day (other types of inhaled corticosteroids combined with long-acting bronchodilators may be prescribed).
• Azithromycin an antibiotic with anti-inflammatory effects to be taken once a day, three times a week.
• Montelukast is an oral drug also used for allergic diseases like allergic rhinitis and asthma, to be taken once every evening.
• For those with more severe condition, systemic immunosuppressive therapy and more advanced medications specific to the patient and condition (outside the scope of this article) may also be considered after discussion with the oncology team.

Follow-up Care

• After initiation of treatment, there will be follow-up in the clinic to monitor compliance, drug administration techniques, and drug-related adverse effects.
• Our respiratory nurses will provide education on techniques for using inhaler therapy and ensure medication compliance, which is essential to prevent further irreversible damage to the lungs.
• Serial monitoring with pulmonary function tests will be arranged, initially in shorter intervals and subsequently spaced out when the condition is stable.
• Your child will be referred to the physiotherapist for breathing exercises to maintain good respiratory status and for regular evaluation of functional status with the six-minute walk test.
• Children are encouraged to participate in regular school activities and exercise as tolerated.
• For those with treatment response and stable pulmonary function over subsequent visits, weaning of FAM therapy can be considered after 6-12 months.
• Patients with severe lung cGVHD may require oxygen or other respiratory equipment. The respiratory team, together with multiple parties, will provide support on arrangement of home equipment and follow-up.

Special Treatment Options available in HKCH

• HKCH provides respiratory services to treat patients with lung conditions holistically. Patients are attended to by a multidisciplinary paediatric team comprising paediatric respiratory specialist, respiratory nurses, pharmacists, and physiotherapists for their acute and long-term respiratory care and rehabilitation.
• The progress of the disease will be closely monitored, and if necessary, multidisciplinary assessments and discussions will be conducted to decide the most appropriate treatment options for each patient.

Acknowledgement

Principal author: Dr Tammy Cheung on behalf of Respiratory Team, HKCH
Initial posting: Mar 2024

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