Current therapeutics for sclerotic and fibrotic manifestations of chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) is a long-term, heterogeneous immunologic complication of allogeneic hematopoietic cell transplantation. A subset of patients with cGVHD develop progressive fibrosis with highly morbid manifestations, including sclerodermatous skin and lung involvement, classically considered bronchiolitis obliterans syndrome. The fibrosis observed with cGVHD involves a complex interplay between immune dysregulation and aberrant tissue repair that is incompletely understood, although the mechanisms of other fibrotic diseases inform our understanding of the pathways involved and likely hold key insights for future therapeutic targets. Current treatment options for cGVHD are broadly approved for all manifestations. Data regarding the efficacy of these therapies for specific fibrotic complications are limited, although more recent trials have begun to specifically evaluate the efficacy and safety of these treatments for lung and sclerotic cGVHD. Furthermore, current methods of evaluating treatment effectiveness in sclerotic or fibrotic disease are generally subjective, and partial responses can vary substantially. Given these challenges, new techniques and technologies are needed to improve assessments of clinical response. Prospective studies adapted and dedicated to these high-risk organ-specific manifestations of cGVHD should be a research priority.