PTCy-based GvHD prophylaxis and BOS risk: A multicenter cohort study

Results from a retrospective, multicenter cohort study, evaluating the association between post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GvHD) prophylaxis and risk of developing bronchiolitis obliterans syndrome (BOS) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), were published in Chest by Eggleston et al. Outcomes were assessed in 900 patients who were alive at 1 year post-transplant (PTCy, n = 276; non-PTCy, n = 624). The primary objective was to compare BOS incidence between patients receiving PTCy-based and those receiving conventional GvHD prophylaxis. 

 Key data: During a mean follow-up of 3.6 years, BOS occurred in 9.1% of patients. Adjusted BOS incidence was 4.0% with PTCy vs 13.0% with non-PTCy regimens (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.09–0.74; p = 0.012). PTCy was also associated with a lower incidence of extrapulmonary chronic GvHD (cGvHD) vs non-PTCy prophylaxis (44.9% vs 61.7%), while extrapulmonary cGvHD conferred an increased BOS risk (HR, 7.27; 95% CI, 3.13–16.9; p < 0.001). Formal mediation analysis suggested that PTCy’s protective effect against BOS may be mediated through prevention of cGvHD; the HR increased from 0.26 (95% CI, 0.09–0.77; p = 0.014) to 0.41 (95% CI, 0.14–1.21; p = 0.108) following adjustment for extrapulmonary cGvHD, representing a 57% attenuation toward the null. 

Key learning: PTCy-based GvHD prophylaxis is associated with a reduced BOS risk after allo-HSCT, with its protective effect likely mediated by cGvHD prevention. These findings support consideration of PTCy-based regimens for patients at high risk of pulmonary complications.