Transpire: Lung Injury in a Longitudinal Cohort of Pediatric Hematopoietic Stem Cell Transplant Patients

Background Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and non-malignant diseases in pediatric patients but comes with significant risk of toxicity. Pulmonary morbidity affects as many as 25% of children receiving transplant. Better diagnostic and treatment modalities for pulmonary complications are greatly needed as survival after HSCT improves. Methods TRANSPIRE is a multi-institutional prospective cohort of pediatric and young-adult patients receiving allogeneic-HSCT (allo-HSCT). Our objective is to identify risk factors and mechanisms of lung injury and test new diagnostic strategies and treatments to reduce morbidity/mortality from lung injury. We are comparing traditional pulmonary function testing to research testing including oscillometry (OS) for patients ≥3 years old, multiple breath washout (MBW) for patients ≥6 years old, home spirometry for patients ≥6 years old and hyperpolarized 129Xenon magnetic resonance imaging (129XeMRI) for patients ≥5 years old. We present our study's progress to date. Results We have enrolled 229 patients across all sites since study opening. Patient characteristics are described in Figure 1. Malignancy was the most common indication for allo-HSCT (n=94, 42.7%). Median age at HSCT was 8.2 years old (range 0.2-24.8 years). We have collected 94.5% of baseline blood samples, 93.6% of day 30 samples and 90.2% of day 100 samples. To date, we have identified 124 pulmonary injury events. The most common events include: viral pathogen identified on nasopharyngeal testing (n=44, 35.4%), clinically significant oxygen supplementation (n=33, 26.7%), and radiologic evidence of pulmonary injury (n=18, 14.5%). We have 108 (95.4%) eligible patients with baseline PFTs, 69 (85.5%) patients with day 100 PFTs and 21 (95.2%) patients with 1-year PFTs. For sites conducting OS, we have 60 (84%) patients who have completed OS at baseline, 32 (82%) patients at day 100 and 14 (74%) patients at 1-year post-HSCT. Fourteen (62.3%) patients have completed MBW testing at baseline, 13 (62.3%) patients at day 100 and 3 (75%) patients at 1-year post-HSCT. For home spirometry, 37 eligible patients were initiated at the day 100 timepoint. Twenty-two (81.4%) patients have completed home spirometry requirements, and 3 (11.1%) patients are still actively completing study requirements. Currently, one site is performing 129XeMRI imaging. Fifteen patients have completed at least one 128XeMRI imaging protocol. We have completed 12 (80%) at baseline, 11 (73.3%) at day 100 and 6 (40%) at the one-year post-HSCT time point. Conclusions Our study demonstrates feasibility of prospective enrollment a large number of pediatric and young adult allo-HSCT patients on a prospective, multi-institutional study. Our study provides an ideal platform to test novel methods of measuring pulmonary function and to trial novel therapies in the future.