Pulmonary complications of allogeneic hematopoietic cell transplantation: Preengraftment

Disease process	Risk factors	Associated manifestations	Radiographic findings	Useful diagnostic tests	Lung biopsy needed
Bacterial pneumonia	Mucositis, neutropenia	Fever, cough, sputum	Usually focal consolidation; becomes diffuse in acute lung injury	Broad microbiologic testing; response to empiric antibiotics	Generally not
Fungal pneumonia	Prolonged neutropenia; exposure to endemic fungi; prior treatment for invasive fungus	Fever	Focal nodular and consolidative opacities, "halo sign," "reverse halo sign"	Broad microbiologic testing including BAL; β-D-glucan of the blood; Aspergillus galactomannan EIA of the blood and BAL fluid; response to empiric antifungal therapy	Sometimes
Aspiration pneumonia	Impaired swallowing due to mucositis; opiate therapy	Fever, dyspnea	Diffuse or focal ground glass or consolidative opacities	Cultures are often negative	No
Permeability pulmonary edema	Aspiration, engraftment syndrome, hyperacute GVHD, sepsis syndrome	Fever, dyspnea	Diffuse ground glass opacities	Normal BNP, normal LV function on echocardiogram	No
Cardiogenic pulmonary edema	Cardiotoxic medications; copious intravenous fluid administration	Dyspnea, weight gain, peripheral edema	Perihilar opacities in butterfly distribution, septal thickening, pleural effusion, cardiomegaly	Elevated BNP; echocardiogram showing reduced LV function	No
Engraftment syndrome		Erythematous maculo-papular rash, fever >38.3°C, weight gain	CT: bilateral ground-glass opacification, hilar or peribronchial consolidation, and thickening of interlobular septa	Skin biopsy; BAL to exclude infection	Sometimes to exclude other treatable causes, lung biopsy shows diffuse alveolar damage
Hyperacute GVHD*	HLA mismatch	Rash, abdominal cramps, diarrhea, elevated bilirubin	Diffuse ground glass consistent with acute lung injury	Skin biopsy; BAL to exclude infection	Sometimes to exclude other processes
Diffuse alveolar hemorrhage			CT: patchy or diffuse opacities, may have air bronchograms	BAL to exclude infection and to identify increasingly bloody return in sequential lavages and >20 percent hemosiderin-laden macrophages	No

BAL: bronchoalveolar lavage; EIA: enzyme immunoassay; BNP: brain natriuretic protein; LV: left ventricular; CT: computed tomography; GVHD: graft-versus-host-disease; HLA: human leukocyte antigens; CTPA: computed tomography pulmonary angiogram.
* Hyperacute GVHD is very rare preengraftment, but may rarely occur at the time of engraftment and overlaps clinically with engraftment syndrome.

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Pulmonary complications of allogeneic hematopoietic cell transplantation: Preengraftment