Pulmonary toxicity following hematopoietic cell transplantation: Is the lung a target organ of graft-versus-host disease?

Purpose of review: Hematopoietic cell transplantation is the only curative option for many patients with malignant and nonmalignant diseases. Noninfectious lung disease occurring early and late after hematopoietic cell transplantation is frequently fatal, responds poorly to standard therapy, and limits the efficacy of this procedure. A clearer understanding of the mechanisms responsible for this complication is paramount to improving outcomes after hematopoietic cell transplantation. Recent findings: Historically, approximately 50% of all pneumonias seen after HCT are attributed to noninfectious causes. Transplantation of cells from allogeneic donors significantly exacerbates the severity of pulmonary toxicity, suggesting that the immunologic dysregulation that occurs in this setting contributes to lung damage and dysfunction. Insights generated from animal modeling suggest that the mechanisms contributing to lung inflammation after allogeneic hematopoietic cell transplantation are similar to those responsible for graft-versus-host disease in other organs. Summary: Experimental and clinical data support the concept that noninfectious pulmonary damage after hematopoietic cell transplantation is related to two distinct but interrelated pathways of immune-mediated injury. Further research into mechanisms of lung injury after hematopoietic cell transplantation should improve our understanding of this disease process and ultimately lead to novel strategies to prevent or treat this frequently fatal complication.