Extended Abstract: Lung Injury after Allogeneic Hematopoietic Cell Transplantation

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly utilized in the treatment of hematologic malignant and non-malignant diseases. Therapy-related toxicity and graft versus host disease (GVHD) remain major challenges as they significantly contribute to treatment related morbidity and mortality. The pathophysiology of noninfectious lung injury is not completely understood and relates to airway disease, interstitial disease, and vessel disease. Bronchiolitis obliterans (BO) and bronchiolitis obliterans syndrome (BOS) are the only accepted diagnostic or distinctive forms of chronic GVHD of the lung in the most recent National Institutes of Health Consensus Development Project. Raised attention to noninfectious lung injury has led to the development of clinical recommendations to include pulmonary function testing in the standard of care follow-up after transplant (1). Earlier studies from our group demonstrate a correlation between the development of clinical GVHD, pulmonary GVHD, and impaired ventilation after allo-HCT, emphasizing that respiratory dysfunction after transplant is partially due to alloreactive tissue injury to the lung (2-7). While acute lung injury potentially sets the stage for chronic lung injury after HCT, additional second hits and involvement of other compartments of the adaptive immune system are probably needed for the progression to BOS/BO as well as to restrictive lung injury and fibrosis. As recently shown, B cells, macrophages as well as profibrotic pathways /BOS, all together likely are involved with each presenting potential therapeutic targets. (8-14).