Pulmonary Function Outcomes in a Prospective Cohort of Pediatric Allogenic Hematopoietic Cell Transplant Recipients

RATIONALE Pulmonary complications following pediatric allogenic hematopoietic cell transplantation (allo-HCT) are a major cause of morbidity and mortality, but longitudinal lung function data are lacking in this population. We aimed to address this knowledge gap. METHODS We analyzed pulmonary function tests (PFTs) from a prospective cohort of pediatric allo-HCT recipients enrolled between 2015 and 2018. PFTs were obtained prior to and after allo-HCT at day 100; at six, nine, and twelve months; and yearly through five years post-transplant. PFT values were interpreted using race-neutral Global Lung Function Initiative Global reference equations. We defined low forced vital capacity (FVC) and low diffusing capacity of the lungs for carbon monoxide (DLCO) as values below the fifth percentile of predicted normal. We defined obstruction as a value below the fifth percentile of predicted normal of the ratio of forced expiratory volume in one second to FVC (FEV1/FVC). We corrected DLCO values for hemoglobin levels obtained at the time of PFT measurement. RESULTS Of the 83 pediatric allo-HCT recipients in the study, 65 (78%) participants had at least one interpretable PFT during the study period (Table 1). Sixty-three (97%) received myeloablative chemotherapy prior to allo-HCT. Of the 50 participants who underwent PFTs prior to allo-HCT, six (12%) had low FVC values, eight (16%) met criteria for obstruction, and eight (16%) had low corrected DLCO values, demonstrating that prior to transplantation, a substantial burden of pulmonary disease exists in this population. Forty-four (68%) children had abnormal spirometry and/or DLCO at any point during the study period. Low DLCO was the most common PFT abnormality among study participants (43%), followed by low FVC (40%) and obstruction (22%). In multivariable logistic regression models, hematologic malignancy was associated with a decreased odds of low FVC and older age was associated with an increased odds of obstruction at any time point. Self-reported Black race and older age were associated with increased odds of low DLCO at any time point. Twelve (18%) children died within 5 years of transplant, five of whom died of pulmonary complications. CONCLUSIONS In a longitudinal cohort of pediatric allo-HCT recipients at a single institution, PFT abnormalities before and after HCT were common. Age, race, and indication for allo-HCT were associated with the odds of lung function abnormalities. Pulmonary causes contributed to over 40% of deaths within five years of transplant. Further research to understand factors affecting lung function loss in this cohort is underway.

Duke Scholars

Author Sweta Patel Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Kris Mahadeo Pediatrics, Transplant and Cellular Therapy

Author Sarah Mabrey Heston Pediatrics, Infectious Diseases