Sirolimus and ruxolitinib in progressive Bronchiolitis Obliterans Syndrome due to chronic Graft-Versus-Host disease

Bronchiolitis obliterans syndrome (BOS) is a pulmonary manifestation of chronic graft-versus-host disease (GVHD) that can occur as a complication in up to 14% of hematopoietic stem cell transplantation (HSCT) recipients. First-line therapy for BOS includes inhaled fluticasone, azithromycin, and montelukast (FAM) in combination with systemic corticosteroids, with or without additional immunosuppressive agents. Although ruxolitinib is a promising second-line therapy for GVHD, pulmonary involvement remains difficult to treat. We describe a 24-year-old male with a history of B-cell acute lymphoblastic leukemia (B-ALL) who underwent HSCT and developed skin, oral mucosa, and upper gastrointestinal GVHD. After nine months of treatment with corticosteroid therapy and ruxolitinib, he developed dyspnea, hypoxia, and cough. Pulmonary function testing showed severe obstruction, leading to a diagnosis of BOS. Progressive disease occurred despite treatment with first- and second-line therapies. FAM therapy was continued, and sirolimus was added as an adjunct therapy with ruxolitinib as a third-line therapy, which resulted in improvement in radiologic and clinical parameters such as pulmonary function testing (PFT). This case highlights the use of adjunctive sirolimus with ruxolitinib as a potential third-line treatment option for steroid-refractory and ruxolitinib-refractory BOS associated with GVHD.