Diffuse Alveolar Hemorrhage in Hematopoietic Cell Transplantation

Diffuse alveolar hemorrhage (DAH) is a morbid syndrome that occurs after autologous and allogeneic hematopoietic cell transplantation in children and adults. DAH manifests most often in the first few weeks following transplantation. It presents with pneumonia-like symptoms and acute respiratory failure, often requiring high levels of oxygen supplementation or mechanical ventilatory support. Hemoptysis is variably present. Chest radiographs typically feature widespread alveolar filling, sometimes with peripheral sparing and pleural effusions. The diagnosis is suspected when serial bronchoalveolar lavages return increasingly bloody fluid. DAH is differentiated from infectious causes of alveolar hemorrhage when extensive microbiological testing reveals no pulmonary pathogens. The cause is poorly understood, though preclinical and clinical studies implicate pretransplant conditioning regimens, particularly those using high doses of total-body-irradiation, acute graft-versus-host disease (GVHD), medications used to prevent GVHD, and other factors. Treatment consists of supportive care, systemic corticosteroids, platelet transfusions, and sometimes includes antifibrinolytic drugs and topical procoagulant factors. Therapeutic blockade of tumor necrosis factor-α showed promise in observational studies, but its benefit for DAH remains uncertain after small clinical trials. Even with these treatments, mortality from progression and relapse is high. Future investigational therapies could target the vascular endothelial cell biology theorized to contribute to alveolar bleeding and pathways that contribute to susceptibility, inflammation, cellular resilience, and tissue repair. This review will help clinicians navigate through the limited evidence to diagnose and treat DAH, counsel patients and families, and plan for future research.