Can Posttransplant Cyclophosphamide Reduce Bronchiolitis Obliterans Syndrome Risk Through Chronic Graft vs Host Disease Prevention?: A Multicenter Cohort Study.

BACKGROUND

Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of pulmonary chronic graft vs 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 < 50%. Posttransplant 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 among patients undergoing allogeneic HCT?

STUDY DESIGN AND

METHODS

We conducted a retrospective multicenter cohort study across 3 US centers between 2015 and 2023 comparing BOS incidence between patients receiving PTCy vs non-PTCy GvHD prophylaxis. BOS was defined as either meeting strict National Institutes of Health 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 with PTCy, 624 without PTCy), PTCy was associated with a 75% reduction in BOS risk (adjusted hazard ratio [HR], 0.25; 95% CI, 0.09-0.74; P = .012) when adjusted for age, immunologic matching status, and baseline FEV1 and stratified by conditioning strategy. Mediation analysis demonstrated that when cGvHD was added to the model, the PTCy HR attenuated from 0.26 to 0.41 (57% attenuation toward the null; P = .108), indicating that cGvHD prevention mediates PTCy's protective effect. Results remained robust after excluding haploidentical transplants (HR, 0.24; 95% CI, 0.07-0.77; P = .016).

INTERPRETATION: Our results show that 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 posttransplant monitoring.