Front Immunol

This study evaluates the incidence and clinical impact of late- onset non-infectious pulmonary complications (LONIPCs) in adults undergoing allo-HCT with post-transplant cyclophosphamide (PTCy). In addition, it assesses the prognostic value of pre-transplant pulmonary function tests (PFTs) for overall mortality in this population. A total of 317 consecutive adults transplanted between 2014 and 2024 were retrospectively included. LONIPC occurred in 10.6% of patients. The most frequent diagnoses were cryptogenic organizing pneumonia (COP, 4.1%), bronchiolitis obliterans syndrome (BOS, 5.9%), and pulmonary thromboembolism (0.6%). Risk factors for LONIPC included smoking history, pre-existing bronchial asthma, mismatched donors, and grade III-IV acute GVHD. The diagnosis of LONIPC was strongly associated with adverse outcomes in both univariate (OS: HR 9.37, P < 0.001; NRM: HR 4.19, P = 0.001) and multivariate analyses (OS: HR 8.07, P < 0.001; NRM: HR 3.19, P = 0.033). Based on pre-transplant PFTs and the HCT-CI scoring system, patients were classified into low- (24.3%), moderate- (35.0%), or high-risk groups (40.7%). High-risk patients had significantly poorer overall survival (OS) (3-year OS: 58.8% vs. 72.0% and 70.0%, P = 0.027) and higher non-relapse mortality (NRM) (3-year NRM: 19.0% vs. 7.9% and 15.1%) compared with those in the low- and intermediate-risk groups. No differences were observed regarding pre-transplant PFTs between patients developing LONIPC and those who did not. In conclusion, the incidence of LONIPC occurs in 10% of adults undergoing allo-HCT with PTCy. Its diagnosis, as well as the presence of significant pre-transplant PFT abnormalities, were associated with worse outcomes, underscoring their prognostic importance in the contemporary PTCy-based allo-HCT setting.