Pulmonary complications after allogeneic hematopoietic cell transplantation: Evaluation

INTRODUCTION — Allogeneic hematopoietic cell transplantation (HCT, also called hematopoietic stem cell transplantation) is the treatment of choice for many hematologic disorders. Pulmonary complications are a common cause of morbidity and occasionally mortality following this procedure [1-5].

The pulmonary complications of allogeneic HCT will be reviewed here. The determination of eligibility for HCT, infectious complications of HCT, supportive care following HCT, and pulmonary complications of autologous HCT are discussed separately. (See "Determining eligibility for allogeneic hematopoietic cell transplantation" and "Overview of infections following hematopoietic cell transplantation" and "Early complications of hematopoietic cell transplantation" and "Survival, quality of life, and late complications after hematopoietic cell transplantation in adults" and "Pulmonary complications after autologous hematopoietic cell transplantation".)

OVERVIEW AND DEFINITIONS — Hematopoietic cell transplantation (HCT) is a general term for a variety of procedures in which the patient is treated with chemotherapy and/or irradiation (ie, the "preparative regimen") followed by the infusion of hematopoietic progenitor cells. Progenitor cells can come from a variety of sources (eg, bone marrow, peripheral blood, cord blood). (See "Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells".)

Allogeneic versus autologous HCT — Allogeneic HCT refers to the use of hematopoietic progenitor cells collected from a relative (which can be human leukocyte antigen [HLA] identical, haploidentical, or mismatched) or an unrelated donor (volunteer or umbilical cord donor). Autologous HCT refers to a collection of hematopoietic progenitor cells from the patient prior to the administration of high-dose chemotherapy designed to target an underlying malignancy, followed by reinfusion of these cells.

Many of the pulmonary complications of allogeneic HCT also occur with autologous HCT, but there are some important differences. Prevention of graft rejection and graft-versus-host disease (GVHD) in allogeneic HCT necessitates more intense immunosuppression than that required for autologous HCT, which does not have these complications. Allogeneic grafts may be associated with development of potentially detrimental GVHD. On the other hand, some allogeneic HCT patients may benefit from a graft-versus-tumor effect. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes" and "Biology of the graft-versus-tumor effect following hematopoietic cell transplantation".)

Autologous HCT is discussed separately. (See "Multiple myeloma: Use of hematopoietic cell transplantation" and "Pulmonary complications after autologous hematopoietic cell transplantation" and "Determining eligibility for autologous hematopoietic cell transplantation".)

Preparative conditioning regimen — Preparative conditioning regimens are designed to ablate or suppress the host bone marrow and thereby prevent graft rejection, but have the potential to cause pulmonary toxicity. Preparative regimens for HCT have been termed myeloablative (eg, total body irradiation ≥5 Gy, high dose busulfan), nonmyeloablative (fludarabine, cyclophosphamide, antithymocyte globulin, irradiation ≤2 Gy), and reduced intensity (eg, low-dose busulfan, melphalan). The various preparative conditioning regimens are discussed in greater detail separately. (See "Preparative regimens for hematopoietic cell transplantation".)

Engraftment — Engraftment after HCT is defined as the attainment of an absolute neutrophil count (ANC) of 1000/microL, or three consecutive days with a count greater than 500. Time to engraftment is variable and dependent on multiple variables, including cell source, graft composition, and type of conditioning.

At the time of engraftment of donor hematopoietic cells, patients may develop a cytokine-driven engraftment syndrome. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Engraftment syndrome'.)

Maintenance immunosuppression — After allogeneic HCT, maintenance immunosuppression is administered to prevent graft rejection and GVHD. A commonly used regimen is the combination of methotrexate and a calcineurin inhibitor such as cyclosporine or tacrolimus; alternative or additional agents include post-transplant cyclophosphamide, glucocorticoids, sirolimus, mycophenolate mofetil, and also agents targeting T-cell depletion. These agents contribute to the risk of pulmonary toxicity and opportunistic infections. (See "Prevention of graft-versus-host disease".)

Graft-versus-host disease — Graft-versus-host disease (GVHD) occurs when immune cells transplanted from a nonidentical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. Hyperacute GVHD, which is very rare with current HLA typing, occurs in the first 14 days post-HCT, acute GVHD in the first 100 days, and chronic GVHD after the first 100 days, although the specific timing is approximate. Despite preconditioning and maintenance immunosuppression to prevent GVHD, a substantial proportion of allogeneic HCT recipients are affected by GVHD. GVHD in turn may increase the risk of certain pulmonary complications, such as the idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, bronchiolitis obliterans, and late-occurring infections. (See "Biology of the graft-versus-tumor effect following hematopoietic cell transplantation".)

APPROACH TO THE PATIENT WITH RESPIRATORY SYMPTOMS OR SIGNS — The approach to evaluating pulmonary complications that occur after allogeneic hematopoietic cell transplantation (HCT) begins with considering the timing of onset of the pulmonary disease (eg, before or after engraftment), the appearance of the chest radiograph (eg, clear, focal opacities, diffuse opacities), and the particular features of the individual patient (table 1 and table 2).

The acuity of illness (eg, fever, tachypnea, hypoxemia, leukocyte counts) should guide the rapidity of the evaluation and the need for empiric antibiotics. Almost all febrile HCT recipients are treated empirically with broad-spectrum antibiotics until a causative organism is identified or an alternate diagnosis is confirmed. The choice of empiric therapy should depend upon the risk for specific infections, the potential sites of infection, and the susceptibility patterns at a given institution (figure 1). (See "Overview of infections following hematopoietic cell transplantation".)

Features that may help direct the evaluation include the following:

●Presence of a maculopapular rash, gastrointestinal symptoms, and a rising serum bilirubin can help identify graft-versus-host disease as a cause of interstitial lung disease. (See "Cutaneous manifestations of graft-versus-host disease (GVHD)" and "Clinical manifestations, diagnosis, and grading of acute graft-versus-host disease".)

●The risk for certain infections can be predicted based on pretransplant serostatus (eg, cytomegalovirus, herpes simplex virus, HIV, varicella-zoster virus, Epstein-Barr virus, toxoplasmosis), prior exposures (eg, cats, birds, mycobacteria, endemic fungi) of the recipient and donor, and also the history of prophylaxis for infectious agents. (See "Overview of infections following hematopoietic cell transplantation", section on 'Risk of infection'.)

●History of timing, dose, and field of radiation therapy delivered to the chest to treat the underlying malignancy or as part of the conditioning regimen, as radiation pneumonitis is a potential cause of respiratory symptoms and signs. (See "Radiation-induced lung injury".)

●Exposure to drugs that cause pulmonary or cardiac toxicity during the pretransplant treatment of the primary disease. (See "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment" and "Pulmonary toxicity associated with antineoplastic therapy: Cytotoxic agents" and "Cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines" and "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity".)

●Knowledge of the current and previous immunosuppressive and chemotherapeutic agents (eg, methotrexate, cyclophosphamide, busulfan, glucocorticoids) helps in assessing the risk of opportunistic infection and the likelihood of lung toxicity due to the agents given. (See "Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and treatment".)

EVALUATION — The initial evaluation of pulmonary complications of allogeneic hematopoietic cell transplantation (HCT) typically includes laboratory testing (eg, complete blood counts, blood cultures, peripheral blood and urine tests for bacterial, viral, and fungal antigens or sequences), pulmonary function testing, and imaging studies (table 1 and table 2). Additional testing is based on the timing of symptom onset, acuity of illness, and the appearance of the chest radiograph.

Laboratory testing — Laboratory testing generally includes assessment of complete blood counts and differential to assess the severity of neutropenia and lymphocytopenia, and also the possibility that anemia is contributing to dyspnea. D-dimer and brain natriuretic peptide levels are sent when thromboembolism or cardiogenic pulmonary edema are suspected.

●Microbiologic tests – Blood cultures are obtained for bacteria and fungi in all HCT recipients with a fever. Nasopharyngeal swabs are sent for polymerase chain reaction (PCR) testing for respiratory viruses (eg, influenza, parainfluenza, respiratory syncytial virus, adenovirus, coronavirus, and others). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the virus that causes coronavirus disease 2019 [COVID-19]) is among the group of respiratory viral pathogens that can cause pneumonia in the post-HCT period. Urinary Legionella and pneumococcal antigen tests are also obtained. (See "Overview of infections following hematopoietic cell transplantation" and "Parainfluenza viruses in adults", section on 'Diagnosis' and "COVID-19: Diagnosis" and "Seasonal influenza in adults: Clinical manifestations and diagnosis".)

Cytomegalovirus (CMV) pneumonitis can occur in the post-engraftment phase, so blood is tested for CMV replication (eg, viral load by PCR) in most patients with fever and radiographic opacities after engraftment. (See "Overview of infections following hematopoietic cell transplantation", section on 'Pneumonia'.)

Serum assays for aspergillus galactomannan, beta-D-glucan, and cryptococcus antigen can be obtained, particularly if nodular opacities are noted on imaging. A more detailed discussion of the evaluation for infection following HCT is provided separately. (See "Overview of infections following hematopoietic cell transplantation" and "Approach to the immunocompromised patient with fever and pulmonary infiltrates".)

Lower respiratory tract sampling may be necessary if the above tests are unrevealing and the patient does not respond to empiric therapy. (See 'Bronchoscopy' below.)

●Autoantibody testing is obtained when rheumatic disease (eg, systemic sclerosis, polymyositis, Sjögren's disease, vasculitis) is suspected on the basis of compatible clinical findings developing late after HCT, Autoimmune disease is rarely reported as a late complication of HCT, most often in patients who received a myeloablative conditioning regimen. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Autoimmune disease'.)

Imaging — A conventional chest radiograph is obtained in virtually all HCT recipients with fever and/or pulmonary symptoms or signs, as the radiographic appearance can help guide the evaluation of pulmonary complications of HCT (table 1 and table 2).

In addition, most patients undergo computed tomography (CT), which is more sensitive than a conventional chest radiograph and may identify subtle abnormalities missed on the conventional chest radiograph [6,7]. Chest CT is also used to characterize the patterns of abnormalities (eg, ground glass versus reticular, nodular versus diffuse) and the exact location [8]. However, the specific radiographic pattern is rarely diagnostic, and many of the pulmonary diseases that follow allogeneic HCT can have multiple radiographic appearances.

●Diffuse pulmonary opacities – After allogeneic HCT, diffuse pulmonary opacities can be caused by a broad spectrum of disease processes, including bacterial, viral (eg, CMV, influenza), or fungal (eg, Pneumocystis) infection, the engraftment syndrome, the idiopathic pneumonia syndrome, diffuse alveolar hemorrhage, interstitial pneumonia due to connective tissue disease, and pulmonary alveolar proteinosis (table 2) [9,10]. Many of these disorders are associated with diffuse ground glass opacities, although CMV, Aspergillus, Pneumocystis, organizing pneumonia, and pulmonary cytolytic thrombi can present with diffuse small nodular opacities.

●Focal pulmonary opacities – Focal or lobar opacities in febrile, allogeneic HCT recipients are often caused by bacterial or fungal infection (eg, Nocardia, aspergillus), but can also be caused by pulmonary thromboembolism or organizing pneumonia. Invasive pulmonary fungal infection should be particularly suspected when there are nodular abnormalities on chest radiograph or CT scan [8,11]. Less common causes of focal radiographic opacities include organizing pneumonia, irradiation pneumonitis (localized to a field of treatment), and recurrent lymphoma.

Nodular opacities without associated fever can be caused by processes such as recurrent lymphoma, posttransplant lymphoproliferative disease, and lung cancer [8]. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Malignancy'.)

●Clear chest radiograph – Following allogeneic HCT, the disease processes that cause dyspnea and a clear conventional chest radiograph include anemia, early Pneumocystis pneumonia, thromboembolic disease, cardiac dysfunction, and airways disease such as bronchiolitis obliterans (BO) [12,13]. Pneumocystis pneumonia and pulmonary veno-occlusive disease may present with a normal chest radiograph, but the chest CT is not normal. Pulmonary thromboembolism (rare) can present with a clear chest radiograph, but the presence of hypoxemia and/or or a positive D-dimer should lead to additional imaging studies. (See "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV", section on 'Radiographic findings' and "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Pulmonary veno-occlusive disease'.)

●Additional imaging studies – When pulmonary thromboembolic disease or pulmonary veno-occlusive disease is suspected (eg, due to a positive D-dimer test, a characteristic pulmonary function test or radiographic pattern, or a degree of hypoxemia out of proportion to the radiographic opacities), either a computed tomography pulmonary angiogram (CTPA) or conventional pulmonary angiogram is obtained. (See "Epidemiology, pathogenesis, clinical evaluation, and diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis in adults", section on 'Venous congestion on chest imaging' and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Catheter-based pulmonary angiography'.)

Pulmonary function testing — The evaluation of dyspnea in stable allogeneic HCT recipients without significant hypoxemia or radiographic opacities usually includes full pulmonary function testing with exercise oximetry and/or arterial blood gas analysis [14]. The results are compared with pretransplant values. (See "Overview of pulmonary function testing in adults" and "Diffusing capacity for carbon monoxide" and "Pulse oximetry".)

The combination of a restrictive pattern and a gas transfer abnormality on pulmonary function testing suggests that interstitial lung disease may be present. These findings should be further evaluated with imaging studies. An HRCT may be necessary to ensure that findings that are too subtle to identify on a conventional chest radiograph are not missed. (See 'Imaging' above.)

The combination of normal lung volumes with a pulse oxygen saturation and diffusing capacity (DLCO) that are lower than expected based on the HRCT findings suggests processes such as pulmonary hypertension, thromboembolic disease, pulmonary cytolytic thrombi, or veno-occlusive disease.

An obstructive pattern with forced expiratory volume in one second (FEV₁) <70 percent may be a nonspecific finding following HCT or may be a manifestation of BO. For patients with suspected BO, spirometry is monitored at one- to three-month intervals; if spirometry is stable for a year, the frequency can be decreased to 6- to 12-month intervals (table 3) [15]. The management of BO is described separately. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Airflow obstruction and bronchiolitis obliterans'.)

Echocardiography — An echocardiogram is obtained when cardiac dysfunction is suspected (eg, diffuse opacities consistent with pulmonary edema) or to assess pulmonary artery pressures when pulmonary veno-occlusive disease or pericardial disease are suspected. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Pulmonary veno-occlusive disease' and "Transthoracic echocardiography: Normal cardiac anatomy and tomographic views" and "Tissue Doppler echocardiography".)

Skin biopsy — The accuracy and predictive value of skin biopsy in the differentiation of engraftment versus GVHD is unclear. (See "Cutaneous manifestations of graft-versus-host disease (GVHD)", section on 'Skin biopsy'.)

Bronchoscopy

Patients with diffuse pulmonary opacities — Bronchoscopy with bronchoalveolar lavage (BAL) is usually performed when imaging shows diffuse or widespread opacities, unless cardiogenic pulmonary edema is strongly suspected or the patient has contraindications to the procedure [5,16,17].

Bronchoalveolar lavage is performed in an area that appears involved based on the radiographic evaluation. To detect alveolar hemorrhage, three sequential lavages (30 to 60 mL aliquots) are obtained to look for progressively more hemorrhagic returns. Samples of BAL fluid are routinely sent for cell count, white blood cell differential, immunofluorescence studies (eg, Pneumocystis), stains (eg, gram, acid-fast), culture (eg, bacterial, mycobacterial, viral, fungal), and multiplex polymerase chain reaction (PCR) for respiratory viruses. Aspergillus galactomannan antigen is sent when there is concern for fungal infection, especially Aspergillus fumigatus, and cytologic evaluation can help define inflammatory processes and malignancy. Cytology can also quantify the amount of hemosiderin laden macrophages if there is concern for diffuse alveolar hemorrhage. If recurrence of disease is suspected, the BAL can be sent for flow cytometry. (See "Basic principles and technique of bronchoalveolar lavage".)

Polymerase chain reaction (PCR) testing of BAL fluid is another highly sensitive technique for identifying CMV but may not be specific for active disease. (See "Overview of infections following hematopoietic cell transplantation", section on 'Pneumonia'.)

The additional diagnostic value of transbronchial lung biopsy (TBLB) in conjunction with BAL is controversial [18,19]. We base the decision to obtain a TBLB on how well the patient is tolerating the bronchoscopy, whether they have risk factors for bleeding from a TBLB, and how well they would tolerate iatrogenic pneumothorax. Often, TBLB cannot be performed due to thrombocytopenia.

Focal opacities — For stable patients with focal opacities on lung imaging, bronchoscopic evaluation may be delayed pending the results of noninvasive cultures, laboratory tests, and empiric antibiotics directed at the most likely infection(s) based on the patient's post HCT phase (figure 1). If the initial cultures and other tests are negative and the patient hasn’t responded to empiric therapy, bronchoscopy is usually performed to obtain BAL and brushing samples from the affected area for cultures, cytology, and possibly flow cytometry. The studies performed on the BAL fluid and endobronchial brushing samples are described above. (See 'Patients with diffuse pulmonary opacities' above.)

Lung biopsy — Rarely, a surgical lung biopsy is performed when the above blood, imaging, and bronchoscopic studies do not yield an explanation for diffuse pulmonary opacities and the patient is not improving with empiric therapy (eg, antibiotics, diuresis, glucocorticoids) [10,16]. The decision to pursue lung biopsy must weigh the likelihood of identifying a treatable diagnosis with risks of the procedure; multidisciplinary discussion can be invaluable in this setting [5]. Lung biopsy may be performed via video-assisted thoracoscopic surgery (VATS) or open thoracotomy. Samples are obtained from an area of disease activity, as determined by computed tomography and sent for histopathologic analysis and bacterial, mycobacterial, fungal, and viral culture. Special stains for mycobacteria and fungi are performed. (See "Role of lung biopsy in the diagnosis of interstitial lung disease", section on 'Surgical lung biopsy'.)

In a case series of 35 hematopoietic stem cell recipients with diffuse pulmonary opacities who underwent open lung biopsy, the most common causes were idiopathic interstitial pneumonia (40 percent), cytomegalovirus pneumonia (20 percent), and organizing pneumonia (14 percent) [10]. Drug reactions were diagnosed in 30 percent, some of whom had organizing pneumonia. The idiopathic interstitial pneumonias found in these patients were diffuse alveolar damage (ie, acute interstitial pneumonia) or nonspecific interstitial pneumonia. (See "Acute interstitial pneumonia (Hamman-Rich syndrome)" and "Treatment and prognosis of nonspecific interstitial pneumonia".)

For patients with lung toxicity due to chemotherapeutic agents or radiation therapy, biopsy findings are nonspecific and include diffuse alveolar damage, type II alveolar epithelial cell atypia and hyperplasia, interstitial pneumonitis, and thickening of the interstitium with early fibrosis. There is usually minimal acute inflammation.

SUMMARY AND RECOMMENDATIONS

●Overview – Several aspects of allogeneic hematopoietic cell transplantation (HCT) contribute to the development of pulmonary disease, including previous treatment of the underlying disease, the pretransplant conditioning regimen (chemotherapy with or without irradiation), engraftment of donor cells, graft-versus-host disease (GVHD), and ongoing immunosuppression. Thus, the pulmonary complications of allogeneic HCT include a broad spectrum of infectious, inflammatory, and neoplastic disorders (table 1 and table 2). (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes".)

●Approach – The approach to evaluating pulmonary complications begins with considering the timing of onset of the pulmonary disease (eg, before or after engraftment), the appearance of the chest imaging studies (eg, clear, focal opacities, diffuse opacities), and certain patient- and donor-specific features such as cytomegalovirus (CMV) serologic status, exposure to animals and endemic fungi, exposure to pneumotoxic drugs and radiation therapy, the underlying disease, and degree of immunosuppression. (See 'Approach to the patient with respiratory symptoms or signs' above and 'Imaging' above.)

●Empiric antibiotics – The acuity of illness (eg, fever, tachypnea, hypoxemia, leukocyte counts) should guide the rapidity of the evaluation and the need for empiric antibiotics. Empiric antibiotics are chosen based on the patient's risk for specific infections, the potential sites of infection, the susceptibility patterns at a given institution, and the cost of the various regimens (figure 1). (See 'Approach to the patient with respiratory symptoms or signs' above.)

●Initial evaluation – The initial evaluation of pulmonary complications of allogeneic HCT typically includes laboratory testing (eg, complete blood counts, brain natriuretic protein [BNP], blood cultures, and also nasopharyngeal swabs, peripheral blood, and urine tests for viral, fungal, pneumococcus and Legionella infection), and a chest radiograph. Additional testing is based on the timing of symptom onset, acuity of illness, and the appearance of the chest radiograph and, in most patients, computed tomography. (See 'Evaluation' above.)

●Heart failure - Cardiac dysfunction may be suspected in the absence of fever, chills, or night sweats, but can present concomitantly with infection; initial assessment includes measurement of brain natriuretic peptide (BNP) and echocardiography. Atrial arrhythmias are very common in this patient population, especially among older adults who undergo transplantation. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Pulmonary edema' and 'Echocardiography' above.)

●Diffuse opacities on lung imaging – For HCT recipients with diffuse opacities on lung imaging, bronchoscopy with bronchoalveolar lavage (BAL) is usually performed, preferably in an area of radiographic abnormality. Samples are obtained to look for alveolar hemorrhage, to identify potential infectious agents, and for cytologic analysis. The additional diagnostic value of transbronchial biopsy in conjunction with BAL is controversial. (See 'Imaging' above and 'Patients with diffuse pulmonary opacities' above.)

●Focal opacities on lung imaging – For HCT recipients with focal opacities on lung imaging, the most likely diagnosis is infection, although organizing pneumonia, radiation pneumonitis, and recurrent lymphoma are included in the differential. After noninvasive cultures and laboratory tests are obtained, empiric antibiotics are initiated based on the infections considered likely for that patient's post-HCT phase (figure 1). If the initial cultures and other tests (eg, PCR of nasopharyngeal swabs for viral infection and microbiologic testing of sputum) are negative and the patient hasn't responded to empiric therapy, flexible bronchoscopy is usually performed to obtain samples from the affected area for microbiologic and cytologic studies. (See 'Imaging' above and 'Focal opacities' above.)

●Surgical lung biopsy for opacities of unclear origin – If the etiology of focal or diffuse radiographic opacities remains unclear after the above testing and the patient is not responding to empiric antimicrobial therapy, a surgical lung biopsy may be needed to secure a diagnosis. (See 'Lung biopsy' above.)

●Dyspnea and chest radiographs without new opacities – Patients with dyspnea and chest radiographs without new opacities following allogeneic HCT may have anemia, pulmonary thromboembolic disease, bronchiolitis obliterans, pulmonary veno-occlusive disease, or cardiac dysfunction. Full pulmonary function testing with arterial blood gas analysis or exercise oximetry can help guide the evaluation. High-resolution computed tomography of the chest is more sensitive than the plain chest radiograph and may detect interstitial disease that was not apparent on the chest radiograph. Echocardiography is often performed to assess for pulmonary vascular disease. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Airflow obstruction and bronchiolitis obliterans' and "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes", section on 'Pulmonary veno-occlusive disease'.)

●Treatment – The treatment of pulmonary complications of allogeneic HCT depends on the specific cause, as described separately. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation: Causes" and "Approach to the immunocompromised patient with fever and pulmonary infiltrates", section on 'Selection of initial therapy'.)