Abstract
Sickle cell disease (SCD) can result in progressive pulmonary dysfunction. The impact of successful hematopoietic cell transplantation (HCT) on lung function is rarely investigated serially long-term. We describe the trajectory of pulmonary function tests (PFTs) in a large group of SCD patients before and after HCT.
Retrospective data was collected on 130 SCD patients ≥5 years old with follow-up ≥1 year post-HCT at 11 Sickle cell Transplant Advocacy and Research (STAR) Alliance centers. Patients included those that met height and PFT requirements per American Thoracic Society (ATS) criteria. Descriptive analysis of disease, HCT characteristics, pre-HCT (n=123) and most recent post-HCT (n=120) PFT data is presented. Comparison between pre- and post-HCT PFT results is described in 113 patients with complete lung function data.
Median age at HCT was 12.2 years (IQR: 8.4-15.8) and follow up 3.5 years (IQR: 2.1-5.7). Most patients had HbSS (85%) with a severe clinical phenotype (65%). Donor was predominantly HLA-matched (88%) and bone marrow (84%) HSC source, and 65% received myeloablative conditioning. With median follow up of 3.0 years post-HCT (IQR: 1.9-5.0; Table and Figure panels A and B), no significant differences were seen between individual pre- and post-HCT spirometry or lung volume values (% predicted or category). PFT category did not significantly change (p=0.215; Figure panel C), with most patients having normal PFTs pre- and post-HCT. Most patients were bronchodilator (BD) unresponsive both at baseline and post-HCT. Overall BD unresponsiveness also remained unchanged (p=0.698) though a higher proportion of post-HCT patients had small airway BD unresponsiveness. The latter change however, was not significant (p=0.170).
In this pediatric retrospective cohort of children with SCD, pulmonary function remained stable after curative HCT without the anticipated disease-related decline over time. Univariable and multivariable analysis for predictors of pulmonary dysfunction in this cohort is ongoing. This is to date the largest analysis of PFT data in SCD patients undergoing HCT, which notably uniformly involved primary analysis of raw data without reliance on center interpretation. The results demonstrate stabilization of PFTs after HCT in SCD patients and support the intervention to prevent pulmonary decline.