Comparative longitudinal analysis of pulmonary function post-pediatric Allo-HSCT: benign vs. malignant diseases and early predictors

Abstract

Pulmonary complications are a major cause of morbidity following pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, longitudinal pulmonary function test (PFT) trajectories and early predictors of dysfunction, particularly the interplay between underlying disease, PFTs, and graft-versus-host disease (GVHD), remain poorly understood. In this retrospective single-center study, we analyzed 233 children undergoing their first allo-HSCT with ≥ 100-day survival. Patients were categorized into benign (acquired aplastic anemia, n = 142) and malignant (leukemia/lymphoma, n = 91) groups. We assessed longitudinal PFTs over 24 months and used Kaplan-Meier and multivariate logistic regression analyses to identify early predictors (including 3-month PFT values and GVHD) for subsequent Obstructive (OVD) and Restrictive Ventilatory Disorders (RVD). Over a median follow-up of 33.1 months, the malignant group exhibited significantly slower FEV1 recovery, greater severity of RVD (P = 0.006) and diffusion impairment (P = 0.040), and higher cumulative incidences of OVD (HR = 3.34, P = 0.013) and RVD (HR = 2.16, P = 0.013). The malignant group also had significantly higher rates of acute (P < 0.001) and chronic GVHD (P < 0.001). In multivariate analysis, the strongest independent predictors for RVD were lower 3-month FVC%pred (OR = 0.85, P < 0.001) and the presence of chronic GVHD (OR = 5.97, P = 0.027). For OVD, predictors were lower 3-month MEF50%pred (OR = 0.95, P = 0.030), acute GVHD (OR = 4.24, P = 0.014), and chronic GVHD (OR = 4.20, P = 0.018). Children with malignant diseases face a higher burden of post-HSCT pulmonary dysfunction, driven by both the underlying disease/treatment intensity and a higher incidence of GVHD. Early post-transplant PFTs (FVC%pred, MEF50%pred) and the development of GVHD are powerful, independent predictors of long-term ventilatory disorders. These findings underscore the need for routine, stratified longitudinal monitoring to facilitate early risk stratification and intervention.