RESUMEN
RATIONALE: Sickle cell disease (SCD) is a monogenetic condition with recurring vaso-occlusive events causing lifelong pulmonary morbidity and mortality. There is increasing access to curative therapies, such as hematopoietic cell transplant (HCT), for people living with SCD. However, more information on pulmonary function in adults with SCD after HCT is needed in order to best guide decisions for HCT and post-HCT care. OBJECTIVE: To test the hypothesis that forced expiratory volume in one second (FEV1), and other pulmonary function testing (PFT) parameters, remain stable three years post-HCT. METHODS: People living with SCD undergoing non-myeloablative HCT in a prospective cohort at the NIH Clinical Center from 2004 - 2019 were evaluated for enrollment. Global Lung Function Initiative reference equations and descriptive statistics were calculated prior to HCT and annually for three years. Six-minute walk distance (6MWD) testing was performed. Generalized estimating equations (GEE) were employed to evaluate inter-individual changes in PFT parameters and 6MWD. RESULTS: Of 97 SCD patients undergoing HCT, 41 (42%) were female with median (25th, 75th percentile) age 31.8 (24.8, 38.0) years. Each year of measurement included the following numbers of subjects available for analysis with PFTs: baseline (97), year 1 (91), year 2 (72), year 3 (55); and the following numbers of subjects available for analysis with 6MWD: baseline (79), year 1 (73), year 2 (57), year 3 (41). Pre-HCT FEV1 was median (25th, 75th percentile) 68.3% (61.3%, 80.3%) and 69.2% (60.8%, 77.7%) three years post-HCT; pre-HCT DLCO 60.5% (53.0%, 66.3%) and 64.6% (55.1%, 73.4%) three years post-HCT. GEE estimated that DLCO %-predicted increased significantly 3.7% (95% confidence interval, 1.0%, 6.3%) and the 6MWD significantly increased by 25.9 (6.6, 45.2) meters three years post-HCT, while there was no significant change in %-predicted FEV1 or FVC compared to pre-HCT. CONCLUSIONS: Overall, PFTs remained stable and there was an improvement in DLCO and 6MWD in this predominantly adult cohort undergoing non-myeloablative HCT for SCD. Allogeneic HCT for SCD may cease the cycle of vaso-occlusive pulmonary injury and prevent continued damage. Multicenter studies are needed to evaluate the long-term lung health effects of HCT for SCD in adults and children.