Long Term Follow-Up Post Allogeneic HSCT
Pulmonary Complications

Updated: October 2010

Significant numbers of patients (15-40%) develop late respiratory complications post allogeneic HSCT. These include infectious complications of the immunocompromised host (not discussed here) and noninfectious complications of the lung. The most common obstructive noninfectious complications include bronchiolitis obliterans (BO), bronchiolitis obliterans organizing pneumonia (BOOP) and idiopathic pneumonia syndrome (IPS). The risk factors for developing respiratory compromise include abnormal pulmonary function pre-transplant, chemotherapy received during the course of the disease, chemo/radiotherapy used in pre-transplant conditioning, immune mediated lung injury (CGVHD), infections and smoking.

The most common sub-type of chronic obstructive pulmonary disease (with reduction of FEV1/FVC) seen in this patient group is Bronchiolitis obliterans (BO) which occurs in up to 14% of this population and is associated with significant morbidity and mortality (up to 50%). BO is characterized by a nonspecific inflammatory injury affecting mainly the small airways. In the early stages it is an obstructive respiratory disease but in the advanced stages has both restrictive and obstructive functional changes. Risk factors include CGVHD, recurrent infections, reduced serum immunoglobulin levels, older age of donor/recipient, busulphan in pre-transplant conditioning and GVHD prophylaxis with Methotrexate. The median onset of symptoms is 1 year post-HSCT. Symptoms include a non-productive cough, wheeze, dysnoea and recurrent respiratory tract infections. Patients may be asymptomatic with abnormal PFTs in 20% of cases. The progress is associated with a gradual decline in respiratory function. CXR is often normal in the early stages and in the later stages reveals changes of hyperinflation. High resolution CT (HRCT) scan in the expiratory phase reveals air-trapping (characteristic mosaic image). Small airways thickening and bronchiectasis may also be seen. The diagnosis of BO can be made when the following diagnostic criteria are met: (1) FEV1/FVC ratio <0.7 and FEV1<75% of predicted value; (2) evidence of air trapping or small airway thickening or bronchiectasis on HRCT; (3) absence of infection in the respiratory tract. Management is based on treatment of CGVHD with immunosuppressive therapy including with corticosteroids (1-1.5 mg/day for 2- 6 weeks) followed by a slow taper over 6-12 months and CSA/FK. The addition of a third immunosuppressive agent such as azathioprine, MMF, thalidomide, infliximab, ATG or the use of Azithromycin (250 mg three times/week has been associated with improvement of pulmonary function in some cases. Prompt treatment of infections and replacement of immunoglobulins (with IVIg when IgG levels <4g/L) may help delay progress of the respiratory compromise. Bronchodilators and inhaled corticosteroids can be used. ECP has been found to be useful in small studies.

BOOP occurs earlier in the course of HSCT, between 1-12 months post transplant with an incidence of <2%. Patients present acutely with fever cough, dysnoea. The CXR reveals patchy peripheral consolidation, ground glass attenuation and nodular opacities PFTs reveal a restrictive pattern with reduced TLC and DLCO. Bronchoscopy and biopsy helps to rule out infection and confirm diagnosis. Despite the lack of evidence systemic or inhaled corticosteroids are considered first line therapy and can result in improvement of the condition.

An idiopathic pneumonia syndrome can be seen within 3 months post transplant. The etiologies include infections (bacterial and viral), radiotherapy, chemotherapy (e.g. Busulfan, bleomycin, BCNU) and CGVHD.

Restrictive defects (with reduction of TLC and possibly DLCO) occur in the early (3-6/12 post-transplant) and are often stable and can improve in the subsequent years post-transplant.

Recurrent sino-pulmonary infections can occur. Replacement of immunoglobulins and smoking cessation can help in the management of these infections.

Recommendations:

• Regular clinical evaluations at least 6 monthly or more frequently in the presence of CGVHD should be performed.
• Smoking cessation should be advocated.
• Pulmonary function testing at 3 months and subsequently yearly post transplant in the presence of CGVHD or symptoms.
• Radiology (CXR, HRCT) to be done based on symptoms or abnormal PFT.
• Referral to respirology is recommended in the presence of abnormal PFT and/or symptoms for management and consideration of BAL and biopsy.

The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use.