DAH can develop following stem cell transplant

This patient has developed diffuse alveolar hemorrhage (DAH) following autologous hematopoietic cell transplantation (HCT), and a bronchoscopy with BAL should be performed to confirm the suspected diagnosis (choice B is correct). The overall incidence of DAH ranges from 1% to 21%, and DAH is one of the few complications that develops more or equally commonly in recipients of autologous transplantation as compared with allogeneic transplantation. DAH can be associated with peri-engraftment respiratory distress syndrome (PERDS). It is thought to be related to capillary permeability during neutrophil recovery and/or infection. DAH is likely a subclassification of the idiopathic pneumonia syndrome, which occurs in the posttransplant period with the presence of alveolar injury, compromised gas exchange, radiographic changes, symptoms and signs of pneumonia, and the absence of infections or other causes for pulmonary dysfunction, such as heart failure and fluid overload. Although thrombocytopenia is often present, it is not directly associated with the process and is not thought to be causal (ie, it is not more common in patients who develop DAH). Risk factors for DAH include advanced age, renal dysfunction, preconditioning with busulfan/fludarabine and melphalan/fludarabine, and lymphoma patients receiving pretransplant external beam radiation to the chest.

Patients usually present in the first 2 to 4 weeks following HCT with dyspnea and hypoxemia, worsening radiographs with alveolar infiltrates, and sometimes a decrease in hemoglobin and hematocrit. Hemoptysis occurs in less than 15% to 33% of patients. Progression of symptoms is rapid. Radiographically, the central regions of the lungs are usually involved with ground glass and consolidation.

The diagnostic procedure of choice for suspected DAH is bronchoscopy with BAL. Typically, the return of fluid gets progressively bloodier with repeated serial aliquots (Figure 2), and/or BAL analysis reveals ≥20% hemosiderin laden macrophages. This can occur even in areas where there is no apparent blood in the airway. Transbronchial biopsies add little to making this diagnosis and are almost always contraindicated in the setting of thrombocytopenia and coagulopathy. Surgical lung biopsy is also not indicated and could be complicated by significant bleeding (choice A is incorrect).

Treatment for HCT-related DAH includes corticosteroids, although this practice is not based on strong data. In one study, survival rates with and without steroids was 33% vs 9%, respectively. The recommended dose of steroids is unclear since some studies using high-dose steroids had worse outcomes than those treated with lower doses. Unlike other causes of DAH, such as those due to pulmonary renal syndromes, cyclophosphamide and other treatment such as rituximab and plasmapheresis are generally not indicated. Thrombocytopenia is not a clear cause of DAH, and generally platelet transfusion is not indicated and does not impact mortality, although it is often done. Recombinant factor VIIa has been tried both intravenous and endobronchially, but the literature does not currently support this approach, and some studies suggest increased clot formation with this. The antifibrinolytic aminocaproic acid has also been tried without success. Prognosis of DAH in HCT is poor with mortality rates as high as 64% to 100%, particularly if respiratory failure develops.

Both autologous and allogeneic HCT recipients are susceptible to opportunistic infections with bacteria and fungi secondary to neutropenia. Aspergillus is certainly a cause of opportunistic fungal infection in neutropenic patients, but the patient is on voriconazole and has such a diffuse presentation radiographically (usually more nodular with cavitation and the "halo" sign) that aspergillus would be less likely, and a galactomannan would not be the diagnostic test of choice (choice D is incorrect). Reactivation cytomegalovirus (CMV) infection is unlikely in an autologous HCT recipient since they are not on cell-mediated immunosuppressive medications and even if this occurred, would not develop this early following BMT; thus, a serum CMV PCR would not be helpful (choice C is incorrect). Although volume overload is very common in the bone marrow transplantation recipient, the recent diuresis and normal BNP would suggest that volume overload and cardiac dysfunction are not the cause of this clinical scenario. Although patients with malignancy are prone to pulmonary embolism, the diffuse parenchymal disease and thrombocytopenia would make this less likely.