Cluster analysis for clinical, radiological, and histopathological profiling in chronic pulmonary graft-versus-host disease

Background: Chronic pulmonary graft-versus-host disease (Pc-GVHD) is a late non-infectious complication of allogeneic hematopoietic stem cell transplantation (HSCT). The aim of the study is to determine whether the application of the International Society for Heart and Lung Transplantation (ISHLT) criteria for chronic STUDY DESIGN AND METHODS: We conducted a retrospective observational study involving patients with hematological disorders who developed late-onset, non-infectious respiratory complications following hematopoietic stem cell transplantation (HSCT). Eligibility criteria were adapted from the guidelines of the International Society for Heart and Lung Transplantation (ISHLT). Chest CT scans were assessed for features indicative of airway disease, interstitial lung disease, and organizing pneumonia-like changes. Cluster analysis was performed using Gower distance. Results: Of the 60 patients initially enrolled, 40 met the inclusion criteria (mean age: 45 years; range: 19-71; 47.5 % male). Pulmonary function tests demonstrated an obstructive pattern in 40 % and a restrictive pattern in 60 % of cases. Chest CT imaging identified airway abnormalities in 60 % and fibrotic-interstitial changes in 30 % of patients. Among the 12 patients with available lung histology, centrilobular pathology was observed, including bronchiolitis obliterans, organizing pneumonia, and peribronchiolar or interstitial fibrosis. Fibrotic changes were more commonly observed in patients with restrictive physiology. Cluster analysis identified two distinct phenotypic groups (silhouette index: 0.4611). Cluster 1 (n = 16) was characterized by obstructive physiology, airway-predominant disease, and limited parenchymal fibrosis. Cluster 2 (n = 24) exhibited restrictive physiology, extensive fibrotic interstitial involvement, and coexisting airway disease. Patients in the restrictive group tended to be younger at the time of HSCT and showed more severe fibrotic changes on both imaging and histology (p < 0.05). Features consistent with organizing pneumonia were similarly distributed between the two clusters. Conclusions: Our findings suggest a substantial overlap between airway and interstitial lung disease phenotypes in late-onset Pc-GVHD, supporting a continuum within its pulmonary manifestations and potentially refining disease classification and management.