First-line treatment with low-dose ruxolitinib, pirfenidone, and low-dose calcineurin inhibitors leads to significant improvement in patients with bronchiolitis obliterans syndrome after allogeneic transplantation

Abstract Introduction Bronchiolitis obliterans syndrome ( BOS ) is a clinical syndrome characterized by new-onset persistent airflow limitation after hematopoietic stem cell transplantation ( HSCT ), which is one of the leading causes of late deaths after HSCT, severely restricting the ability of patients to perform their daily activities and reducing their quality of life. Traditional treatments for BOS rely on glucocorticoids combined with FAM regimens ( fluticasone + azithromycin + montelukast ) and calmodulin phosphatase inhibitors ( CNIs ), but they have limited efficacy with an even lower overall remission rate ( ORR ) and poor prognosis once progression to steroid-refractory cGVHD (SR-cGVHD) is achieved. Therefore, there is an urgent need to explore new treatments and strategies. Methods A retrospective analysis of 14 patients, 11 males and 3 females, with a median age of 19 years (7-54 years), who underwent hematopoietic stem cell transplantation combined with BOS at Henan Cancer Hospital from 2018 to 2025, including 6 cases of mild BOS, 3 cases of moderate BOS, 5 cases of severe BOS, Among them, 6 cases of mild, 3 cases of moderate, and 5 cases of severe BOS were treated with low-dose rucotinib ( 5 mg qd po) combined with piroxicam (200 mg tid po), small-dose CNI (half of the effective therapeutic concentration), and FAM first-line treatment. Patients' lung function was assessed at one and three months after treatment, with first-second forced expiratory volume (FEV1) as the primary study endpoint, and secondary endpoints including best-remission rate (BOR) at three months, no recurrence rate (NRM) at 1 year, overall survival (OS) at 1 year, and treatment-related adverse events. Results After three months of treatment, no patients had worsened according to the NIH scale. 35.7% (5 patients) had stable disease, 14.5% (2 patients) achieved partial remission (PR), and 50.0% (7 patients) achieved complete remission (CR).In terms of lung function, FEV1 improved in 85% of patients, with the largest improvement being 27.5% and the smallest only 2.6%. Only two patients showed a decrease in FEV1 (both patients had severe BOS). the 3-month best-remission rate was 64.5%, the 1-year NRM rate was 7.1% ± 6.9%, and the 1-year OS was 92.9% ± 6.9%. In terms of safety, no serious pulmonary infections occurred and no hematologic adverse events were observed. Conclusions In conclusion, the first-line treatment of BOS patients with low-dose ruxolitinib in combination with pirfenidone, low-dose CNI, and FAM had better efficacy and safety, and improved the overall survival of patients.Keywords Low-dose ruxolitinib, pirfenidone, low-dose calcineurin inhibitors, bronchiolitis obliterans syndrome, allogeneic transplantation