Risk Factors for Alloimmune Lung Syndromes after Allogeneic Hematopoietic Cell Transplantation in Children

The non-infectious pulmonary complications idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS) are important causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). To identifying risk factors for these complications, we retrospectively analyzed baseline characteristics and longitudinal data from 633 pediatric and young adult allo-HCT recipients. Risk factors for IPS included non-malignant diagnosis (HR 2.97; 95% CI 1.27–6.97; P=0.01) and adenovirus reactivation (HR 2.75; 95% CI 1.24–6.14; P=0.01). Conditioning with busulfan-cyclophosphamide ±melphalan (BuCy ±Mel) associated with increased IPS risk compared to busulfan-fludarabine ±clofarabine (HR 5.15; 95% CI 2.36–11.24; P<0.001) and non-myeloablative regimens (HR 9.78; 95% CI 2.48–38.61; P=0.001). BuCy ±Mel conditioning also related to increased BOS risk relative to total body irradiation (TBI)(HR 5.11; 95%CI 1.65–15.83; P=0.005) and non-myeloablative regimens (HR 19.68; 95% CI 2.53–155.76; P=0.005). Moreover, elevated endothelial activation and stress index (EASIX), white blood cell, and lymphocyte counts before day 100 post-transplant correlated with IPS. For BOS, high EASIX and increased activated or effector memory CD4+ T-cells were additional significant correlates. In conclusion, IPS and BOS were associated with both distinct and overlapping risk factors in this study. These findings may inform future strategies to identify high-risk patients and develop targeted preventive interventions.