Yadav, H.

Abstract RATIONALE: Allogeneic hematopoietic stem cell transplant (alloHSCT) is the only curative therapy for multiple hematological malignancies and bone marrow failure syndromes. Graft versus host disease (GvHD), remains one of the leading causes of morbidity and mortality. Bronchiolitis obliterans syndrome (BOS) is the canonical manifestation of chronic GvHD of the lungs, occurring in 3-10% of alloHSCT recipients and conferring poor prognosis. There has been a recent paradigm shift towards using post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis resulting in dramatic decreases in both acute and chronic GvHD compared to traditional regimens using methotrexate and tacrolimus. The effect of PTCy on the development of BOS is not well-studied. METHODS: We performed a retrospective cohort study comparing the cumulative incidence of BOS between 93 patients receiving PTCy and 154 patients receiving non-PTCy containing regimens for GvHD prophylaxis between 2015 and 2023 at a single center (Mayo Clinic, Rochester, MN). Patients were included if they were ever diagnosed with BOS or if they survived and were followed for at least 1 year. BOS was diagnosed using 2014 National Institutes of Health criteria. Patients who met 3 of 4 diagnostic criteria were included if a clinical diagnosis of BOS was made. We performed a competing risks time-to-event analysis to compare the incidence of BOS (or death) between the two cohorts. Outcomes were not adjusted for HSCT type (related, unrelated, or haploidentical [HID]) due to a high degree of collinearity with GvHD prophylaxis strategy. RESULTS: Combined cohorts were median age 55 (40-63), 56% male, and 43% ever smokers. Transplants involved HID donors (59% of PTCy cohort, zero non-PTCy), matched related (10% of PTCy, 44% of non-PTCy), matched unrelated (20% of PTCy, 51% of non-PTCy), and mismatched unrelated donors (11% of PTCy, 5% of non-PTCy). Three-year cumulative incidences of BOS among PTCy and non-PTCy recipients were 7% and 14%, respectively (subdistribution HR 0.52 [95% CI 0.21-1.29], P=0.159). For those who received PTCy, incidence of GvHD was smaller (subdistribution HR 0.64 [95% CI 0.46-0.99], P=0.006) with fewer organs involved (1 versus 2, P=<0.0001) and fewer immunosuppressive therapies employed for treatment (2.0 versus 2.5, P=0.01). CONCLUSION: PTCy may reduce risk of BOS among patients undergoing HSCT. Findings are limited by important differences between the cohorts, such as HCT type, and by small sample size. As PTCy is now increasingly used for non-HID transplants, future studies are needed to examine the effect of PTCy on the development of BOS.