C47-28 Impact of PFT Parameters on Survival in a Contemporary Multicenter Cohort of Patients With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell Transplant

Rationale Bronchiolitis obliterans (BOS) following allogeneic hematopoietic cell transplant (allo-HCT) is a highly morbid pulmonary manifestation of chronic-graft-versus-host disease (cGVHD). Historical single-center retrospective studies have reported survival of less than 50% at 5-years post-diagnosis. The aim of this study was to characterize BOS outcomes in a contemporary cohort and assess the association of post-BOS pulmonary function test (PFT) parameters with overall survival (OS). Methods We conducted a multicenter retrospective study of allo-HCT recipients from the Fred Hutch Cancer Center, MD Anderson Cancer Center, and Stanford University. Patients who met NIH criteria for BOS from 2000-2024 were included. All post-BOS PFTs were analyzed. Percent predicted (pp) values were calculated using the 2022 Global Reference Equations. Cox proportional hazards models were used to evaluate associations between PFT parameters (each modeled as a continuous linear time-varying covariate) and outcome, with hazard ratios (HR) presented in terms of an absolute decrease of 10 percentage points of pp. Results From 2000-2024, 433 patients were diagnosed with BOS. Median ppFEV1 at time of diagnosis was 57% overall, and 54% among patients diagnosed pre-2010 vs 59% for those diagnosed from 2010-2024 (CI for difference, 0-11%). Point estimates of OS were 69% (CI 65-73%) and 54% (CI 49-59%) at 2- and 5-years following BOS diagnosis, respectively. The HR of death in the 2010-2024 cohort was 29% less than the pre-2010 cohort (HR 0.71, CI 0.55-0.92; p = 0.009). Survival curves are presented in Figure 1. In univariate analyses, HRs for mortality for each absolute decrement of 10% were: ppFEV1 (HR 1.46, CI 1.35-1.57), ppFVC (HR 1.45, CI 1.36-1.55), ppFEF25-75 (HR 1.31, CI 1.18-1.44), ppDLCO (HR 1.35, CI 1.26-1.45), and ppTLC (HR 1.09, CI 1.01-1.17). An absolute increase of 10% in ppRV led to HR 1.05 (CI 1.03-1.06). When considering pairs of PFT parameters, multivariable Cox models identified meaningful statistical interactions among spirometric parameters, indicating that the mortality risk associated with a given parameter varies across values of other parameters. No interaction was observed between ppDLCO and ppFEV1 and, after adjustment for other parameters, HRs for mortality ranged from 1.13-1.36 (lower confidence limits 1.04-1.27). Conclusions OS following BOS diagnosis in allo-HCT recipients has improved. Declines in PFT parameters are associated with elevated mortality risk and ppDLCO remains a risk factor, even after adjusting for other parameters. Interactions between spirometric measures indicate that the relationship between a given parameter and mortality varies according to the values of other spirometric measures. This abstract is funded by: NIH - R01HL161037