A High Proportion of Abnormal Pulmonary Baseline Investigations in Pediatric BMT Patients: Prospective, Multi-Center Results from the Transpire Study.

Background Pulmonary complications after allogeneic bone marrow transplant (BMT) are significant sources of morbidity and mortality. Pre-BMT pulmonary status may be a predictor of patient outcome, and can be affected by underlying diagnosis, age and prior therapy received. Methods Patients enrolled on TRANSPIRE (a multi-center, prospective cohort of pediatric and young-adult allogeneic BMT patients) underwent uniform pre-BMT pulmonary testing with pulmonary function tests (PFTs) (spirometry, diffusing capacity, 6-minute walk test (6MWT)), chest CT and bronchoscopy/BAL if clinically indicated. Investigation results and clinical history were reviewed by local pulmonologist PI to classify patient as normal or abnormal baseline pulmonary status. Results 146 patients were enrolled at 3 centers over a 20-month period; 147 transplants were received. The median age at BMT was 7 years (0.25-24yo). The most common indication for transplant was malignancy (n=55, 37.7%), followed by immunodeficiency (24%) and marrow failure (17.1%) (Table 1).63 patients (43%) were classified as abnormal baseline pulmonary status. There patients were older (median age 10yo vs 6yo, p-value=0.036 (two-tailed t-test)) (Table 1). There was no difference by gender. The underlying diagnosis type with the highest rate of abnormal baseline was immunodeficiency, with 54% of patients identified as abnormal baseline, p-value 0.17 (Fisher's exact test)) (Table 1, Fig 1A). Only 9% of patients with underlying genetic/metabolic diagnosis had an abnormal baseline, and 40%, 44% and 45% for malignancy, bone marrow failure and benign hematology respectively. Of the immunodeficiency patients with abnormal baseline (n=19), 16 had abnormalities on CT (84%), 11 had abnormal clinical history (57%) and 5 had abnormal BAL/bronchoscopy findings (positive gram stain, positive culture (H.infl), bronchitis, neutrophilia) (Fig 1B).On review of the patients who were classified as abnormal baseline pulmonary status, the most common abnormal finding was on CT (71%), followed by history (54%) and 6MWT (44%), spirometry (31%), and diffusing capacity (15%) (Table 2). Abnormal baseline spirometry was mostly restrictive pattern (50%). Four patients (17%) had severe PFT abnormalities, 9 (37%) moderate and 11 mild (46%) (Table 2).A total of 136 baseline CT scans were performed. 69 (51%) were abnormal. This includes patients with milder abnormalities who were not classified by their pulmonary PI as ‘abnormal’. Common CT abnormalities include atelectasis and nodules. 23 CT scans were performed under general anesthetic (17%); of these, 15 (65%) were reported abnormal, 12 due to atelectasis (Table 2). Conclusion A high proportion of children and young adults have abnormal pulmonary function before the start of BMT conditioning. Future studies will include assessing the impact of these baseline findings on transplant outcome.