Abstract Background Pleuroparenchymal fibroelastosis (PPFE) is a rare and fatal late-onset noninfectious pulmonary complications (LONIPCs) following allogeneic hematopoietic stem cell transplantation (HSCT). The clinical characteristics and risk factors for PPFE after HSCT remain unclear. This study aimed to investigate the incidence, clinical course, and potential risk factors of PPFE using a multicenter retrospective cohort in Japan. Methods We analyzed 1,214 HSCT recipients (2005-2023) across four institutions. Patients with a follow-up shorter than 100 days or insufficient data were excluded. LONIPCs, including bronchiolitis obliterans syndrome (BOS), organizing pneumonia (OP), interstitial lung disease (ILD: excluding OP and PPFE), and PPFE, were diagnosed by multidisciplinary review according to established criteria. Cumulative incidence was estimated by Fine-Gray competing risk analysis, with death as a competing event. Time-dependent Cox regression was used to assess the association between chronic graft-versus-host disease (cGVHD) and PPFE onset. Results Among 1,214 HSCT recipients, 197 (16.2%) developed LONIPCs, including 16 (1.3%) PPFE cases. The median time to PPFE onset was 93 months after HSCT, and 63% of patients died or underwent lung transplantation within two years after diagnosis. The cumulative incidence of PPFE was significantly higher in umbilical cord blood transplantation (UCBT) than in bone marrow or peripheral blood stem cell transplantation (Fine-Gray p = 0.002; subdistribution HR 3.66, 95% CI 1.34-9.95). Total body irradiation (≥8 Gy) showed a trend toward increased risk but was not statistically significant. In time-dependent Cox analysis, cGVHD was not significantly associated with PPFE development (HR 0.9, 95% CI 0.3-2.7). Longitudinal analysis of PPFE cases showed accelerated decline in FVC approximately five years before clinical diagnosis (Segmented Regression Analysis p = 0.009). Conclusions PPFE occurred in approximately 1-2% of allogeneic HSCT recipients, typically presenting as a very late-onset complication (median 8 years post-transplantation) and associated with poor prognosis. UCBT was identified as a significant risk factor for PPFE, while cGVHD showed limited involvement. These findings suggest distinct mechanisms in PPFE pathogenesis after UCBT. Regular long-term pulmonary function monitoring may help in early detection among high-risk recipients. This abstract is funded by: None
Kondo et al. (Fri,) studied this question.