Pleuroparenchymal fibroelastosis after allogeneic hematopoietic stem cell transplantation: Risk factors and longitudinal pulmonary function trajectories in a multicenter cohort.

Pleuroparenchymal fibroelastosis (PPFE) is an uncommon but serious late pulmonary complication after hematopoietic stem cell transplantation (HSCT), frequently resulting in the need for lung transplantation and contributing substantially to mortality. However, its risk factors and prediagnostic pulmonary function trajectory remain poorly defined. This multicenter retrospective cohort study included 1818 patients who underwent allogeneic HSCT between 2005 and 2023. PPFE was diagnosed using established clinical criteria. Cumulative incidence was estimated treating death as a competing event, risk factors were evaluated using cause-specific Cox models, and prediagnostic pulmonary function trajectories were analyzed using mixed-effects and segmented regression models. During a median follow-up of 42.5 months, 306 patients developed late-onset noninfectious pulmonary complications (LONIPCs), including 19 with PPFE. Although the overall incidence of LONIPCs did not differ by graft source, umbilical cord blood transplantation (UCBT) was associated with higher cumulative incidence of PPFE. In an adjusted cause-specific Cox analysis, UCBT remained associated with PPFE, whereas chronic graft-versus-host disease was not significantly associated. PPFE occurred late after transplantation and was preceded by accelerated %FVC decline approximately four years before clinical diagnosis. These findings suggest that extended pulmonary function surveillance may support earlier detection of PPFE in selected high-risk HSCT recipients.