A 20-year-old man received Allo-SCT for acute myeloid leukemia in August 2012. Allo-SCT was successful with good engraftment and the patient had no specific symptoms representing acute rejection. Post-transplant GVHD prophylaxis was performed with tacrolimus. His pulmonary function tests (PFT) prior to bone marrow transplantation were normal, as indicated by forced expiratory volume in 1 (FEV₁)/the forced vital capacity (FVC) = 0.94, FEV₁ = 4.69 L (130% predicted), and FVC = 4.97 L (127% predicted). About one year after Allo-SCT, he presented with dyspnea, general weakness, and erythema with erosions on the hard palate and lips. On chest CT during admission, consolidation mixed with ground-glass opacity lesions along the bronchovascular bundles in both sides of the lungs were thought to be a manifestation of bronchiolitis obliterans organizing pneumonia (BOOP); however, he had no fever, and there was no clinical or laboratorial evidence of infection. He had been diagnosed with chronic GVHD-extensive (involving the eyes, mouth, liver, and lung-BOOP). After treatment with high-dose glucocorticoids, the symptoms of chronic GVHD were resolved, enabling his discharge. Six months later, in March 2014, he was hospitalized due to aggravation of dyspnea, and during hospitalization, he complained of sudden chest pain which was thought to be an aggravation of noninfectious pulmonary complications of chronic GVHD. Crepitus was heard over the anterior chest wall and lower neck on physical examination, and PFTs showed a mixed pattern (severe obstruction of the small airways and a restrictive pattern), as indicated by FEV₁/FVC = 0.36, FEV₁ = 1.08 L (25% predicted), and FVC = 3.04 L (59% predicted). Chest radiograph showed pneumomediastinum and subcutaneous emphysema (Fig. 1A). Chest CT scan demonstrated extensive subcutaneous emphysema along both sides of the neck and chest wall, pneumomediastinum extending to the upper, middle, and posterior mediastinum, and pulmonary interstitial emphysema (Fig. 1B-D). Not only multifocal patchy ground-glass opacities along the bronchovascular bundles, but also newly developed bronchiectasis and a mosaic pattern of lung attenuation mixed with paucity of pulmonary vasculature suggesting BO were noted. Because there was no history of trauma and no predisposing factor for pneumomediastinum, in spite of normal esophagography, he was finally diagnosed with thoracic ALS as a late-onset noninfectious pulmonary complication associated with chronic GVHD in an Allo-SCT recipient. The patient was treated with steroid pulse therapy and he underwent conservative treatment including high-flow oxygen and bronchodilators. Subcutaneous emphysema and pneumomediastinum resolved completely, and he was discharged after one month of treatment. However, 8 months after discharge, he presented with severe dyspnea and subsequent PFTs showed worsened findings as indicated by FEV₁/FVC = 0.23, FEV₁ = 0.53 L (12% predicted), and FVC = 2.28 L (44% predicted). Despite intensive treatment for 2 months after hospitalization, he died due to respiratory failure associated with aggravation of GVHD, approximately 27 months after Allo-SCT.

The following is another case of thoracic air-leakage syndrome (ALS) associated with GVHD. A 58-year-old man received allogeneic peripheral blood stem cell transplantation for the treatment of acute lymphoid leukemia in November 2009. Allo-SCT was successful, with good engraftment, and the patient had no specific symptoms representing acute rejection. Post-transplant GVHD prophylaxis was performed with tacrolimus. He was doing well, but approximately three years later he presented with cough, sputum, and dyspnea. He underwent chest CT, and tubular bronchiectasis was detected with bronchial wall thickening in the lobar and segmental bronchi in all five lobes, and a mosaic pattern of lung attenuation suggesting BO was also noted (Fig. 2A). PFTs showed a severe obstructive pattern of the small airways, as indicated by FEV₁/FVC = 0.26, FEV₁ = 0.87 L (29% predicted), and FVC = 3.38 L (82% predicted). He had no fever, and there was no clinical and laboratorial evidence of infection. Clinically, he had been diagnosed with BO as a manifestation of noninfectious pulmonary complications of chronic GVHD and treated with high-dose steroids. One and a half years later, in April 2014, he experienced sudden chest and neck pain, and crepitus could be heard over the neck and anterior chest wall on physical examination. The subsequent PFTs showed worsened findings due to severe obstruction, as indicated by FEV₁/FVC = 0.22, FEV₁ = 0.68 L (23% predicted), and FVC = 3.06 L (75% predicted). Chest radiograph demonstrated subcutaneous emphysema and pneumomediastinum as well as hyperinflation (increased radiolucency) of both sides of the lungs. On chest CT, newly developed pneumomediastinum and subcutaneous emphysema were noted in the lower neck and upper thoracic cage and progression of bronchiectasis in the underlying BO was also noted on follow up chest CT images (Fig. 2B, C). No causes of air leakage were found in the thorax, and he was diagnosed with thoracic ALS as a late-onset noninfectious pulmonary complication associated with chronic GVHD in an Allo-SCT recipient. The patient was treated with steroid pulse therapy and conservative treatments, including high-flow oxygen and bronchodilators. Subcutaneous emphysema and pneumomediastinum completely resolved, and he was discharged after one month of careful treatment. However, seven months later, he presented with sudden, severe dyspnea. Despite intensive treatment for 3 weeks after hospitalization, he died due to respiratory failure associated with aggravation of GVHD approximately 62 months after Allo-SCT.