Bronchiolitis obliterans complicating bone marrow transplantation

A 19-year-old woman with extensive, persistent chronic graft versus host disease (GVHD), following an HLA-identical bone marrow graft for acute leukemia, developed rapidly progressive airflow obstruction 140 days post-transplantation (PT) and presented clinically with persistent cough, inspiratory rales, bronchospasm and exertional dyspnea. Pulmonary function tests (PFT) showed rapidly evolving severe airflow obstruction and hypoxemia without restrictive ventilatory defect. Open lung biopsy on the 204th day PT confirmed focal bronchiolitis obliterans. On the 381st day PT, she remained clinically stable. Chest x-ray film showed mild overinflation, but was otherwise unremarkable. PFT's continued to show very severe airflow obstruction without restrictive ventilatory defect. The etiology of the obliterative bronchiolitis might be explained on the basis of a direct immunologic reaction mediated by GVHD or possibly a joint viral-GVHD interaction. Awareness and further detailed documentation and analysis of this unusual respiratory syndrome associated with marrow transplant recipients may help clarify the role of GVHD in the development of lung disease in recipients of marrow grafts.