Chest. 2026 Mar 16:S0012-3692(26)00306-5. doi: 10.1016/j.chest.2026.01.031. Online ahead of print.
ABSTRACT
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of pulmonary chronic graft-versus-host disease (cGvHD) that occurs in around 10% of allogeneic hematopoietic cell transplant (HCT) recipients and confers poor prognosis with survival rates at 5-years of less than 50%. Post-transplant cyclophosphamide (PTCy) has emerged as an effective GvHD prophylaxis that reduces overall cGvHD incidence, but its specific impact on BOS risk remains unclear.
RESEARCH QUESTION: How does PTCy affect the rate of BOS amongst patients undergoing allogeneic HCT?
STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study across three U.S. centers between 2015-2023 comparing BOS incidence between patients receiving PTCy-based versus non-PTCy GvHD prophylaxis. BOS was defined as either meeting strict National Institutes of Health (NIH) criteria (4 of 4) or meeting 3 of 4 criteria with clinical BOS diagnosis. We used competing risk regression accounting for death and performed mediation analysis to evaluate whether cGvHD reduction mediates PTCy's protective effect.
RESULTS: Among 900 patients (276 PTCy, 624 non-PTCy), PTCy was associated with a 75% reduction in BOS risk (adjusted HR 0.25, 95% CI: 0.09-0.74, p=0.012) when adjusted for age, immunologic matching status, and baseline forced expiratory volume in 1 second (FEV1) and stratified by conditioning strategy. Mediation analysis demonstrated that when cGvHD was added to the model, the PTCy hazard ratio attenuated from 0.26 to 0.41 (57% attenuation toward the null, p=0.108), indicating that cGvHD prevention mediates PTCy's protective effect. Results remained robust after excluding haploidentical (HID) transplants (HR: 0.24, 95% CI: 0.07-0.77, p=0.016).
INTERPRETATION: PTCy significantly reduces BOS risk through prevention of cGvHD, expanding current evidence of PTCy's benefits beyond overall cGvHD reduction to include protection against this often fatal pulmonary complication. These findings support consideration of PTCy-based regimens for patients at high risk of BOS and may inform risk stratification strategies in post-transplant monitoring.
PMID:41850483 | DOI:10.1016/j.chest.2026.01.031