Breathing New Life into an Old Problem: Pulmonary Complications after Autologous Hematopoietic Stem Cell Transplant

Background Pulmonary complications are a major cause of morbidity and mortality in children undergoing autologous and allogeneic hematopoietic stem cell transplant (HSCT). Pulmonary complications are likely underreported in pediatric patients. Our goal was to describe the incidence and spectrum of pulmonary complications after autologous HSCT (auto-HSCT) in a large cohort of pediatric patients. Methods We completed a retrospective cohort analysis cohort study evaluating a consecutive cohort of pediatric patients who receiving auto-HSCT at the University of Minnesota (UMN) and Cincinnati Children's Hospital Medical Center (CCHMC) between January 2012 and June 2022 and had at least 1 year of post-transplant follow-up. Patient records were reviewed to determine the incidence of non-infectious and infectious pulmonary complications after auto-HSCT. Results We identified 252 patients receiving auto-HSCT at UMN and CCHMC. Patient demographics and transplant characteristics are described in Figure 1. Median age at last HSCT was 5.4 years (range 0.7-39.1 years). Fifty-three (29.4%) patients had abnormal findings in their chest imaging prior to their first auto-HSCT. Only 71 (31.5%) patients had baseline pulmonary functional testing (PFT), with the most common reason for not completing PFTs being age. Twenty-six (11.9%) patients had a baseline pulmonary issue preceding first transplant. A significant proportion of patients had at least one abnormal finding imaging (n=105, 49.7%) seen on baseline pulmonary imaging before first transplant. All pulmonary complications are outlined in Figure 2. Twenty-eight (11.1%) patients required intensive care unit admission for respiratory failure. Mechanical ventilatory support was required by 26 (10.3%) patients. Pulmonary hypertension was identified in 9 (3.6%) patients with all cases being diagnosed after day 100 from last transplant. Diffuse alveolar hemorrhage was identified in 7 (2.8%) patients, with the majority of cases identified as a late complication (n=5, 71.4%). Cryptogenic organizing pneumonia was identified in five (2%) patients and idiopathic pneumonia syndrome in four (1.6%). Veno-occlusive disease was diagnosed in 13 (5.2%) patients, with all cases occurring in the early period. We identified numerous respiratory viral pathogens within this cohort, likely at least in part due to young age. Rhinovirus was the most frequent viral pathogen (n=44, 34.6%), followed by influenza (n=14, 11%). Bacterial infections were less common (n=8, 6.2%). Fungal infections were frequent in the early period after last transplant (n=18, 31.6%). Conclusions Pulmonary complications are common in pediatric patients after autologous HSCT. Patients receiving auto-HSCT require consistent routine baseline and follow-up pulmonary surveillance after auto-HSCT, similar to patients who complete allogeneic-HSCT.