Pulmonary Function before and after Hematopoietic Cell Transplant in People Living with Sickle Cell Disease

Background People living with sickle cell disease (SCD) have increasing access to hematopoietic cell transplant (HCT). However, there are insufficient data on the effects of HCT, and other curative therapies, on pulmonary function in this population. Unlike patients with cancer, individuals with SCD have a lifelong genetic condition with recurring vaso-occlusive events and inflammatory processes known to cause significant pulmonary morbidity. Therefore, studies that report lung function after transplant in cancer survivors may not apply to individuals with SCD. Indeed, data are needed to evaluate the late lung health effects of HSCT in the SCD population. We hypothesized that percent predicted forced expiratory volume in one second (FEV-1), a pulmonary function outcome measure which has been found to be associated with early death in SCD, would be stable one-year post HCT.

Methods People living with SCD who underwent first-time HCT, including HLA-matched sibling and haploidentical HCT, at the NIH Clinical Center from 2004 to 2019 with Hgb SS, SC, Sbeta⁺ thalassemia, and Sbeta⁰ thalassemia with available pulmonary function data were included in this study. Global Lung Function Initiative reference equations were used, and descriptive statistics were calculated for FEV-1, forced vital capacity (FVC), FEV-1/FVC, total lung capacity (TLC), and diffusing capacity of the lungs for carbon monoxide (DLCO) for patients with pre- and one-year post-HCT. Generalized estimating equations were employed to evaluate inter-individual changes in percent-predicted FEV-1 pre- and one-year post-HCT.

Results Seventy-seven people living with SCD (HgbSS n=69 [90%], HgbSC 2 [3%], HbSbeta⁺ 2 [3%], HbSbeta⁰ 4 [5%]) underwent non-myeloablative HCT (HLA-matched sibling n=53 [69%%] and haplo-identical n=24 [31%]) . Of these, 42 (42%) were female with median (25^th, 75^th percentile) age 31.0 (24.0, 37.0) years; there were four patients less than 18 years old. Median (25^th, 75^th) percent predicted forced expiratory volume in one second (FEV-1) was 68.4% (61.3%, 79.1%) at baseline and 69.9% (60.5%, 78.2%) one-year post-HCT; baseline median (25^th, 75^th) percent predicted DLCO was 48.0 (43.0, 54.0) and 48.0 (45.0, 56.0) one-year post-HCT. There was no significant change in percent predicted FEV-1 (0.88 (0.78, 2.55; p=0.30) one-year post-HCT.

Conclusion Pulmonary function remained stable in people living with SCD one-year post-HCT. Allogeneic HCT for SCD may cease the cycle of vaso-occlusive injury to the lung tissue and airway system and prevent continued damage. In addition, it is possible that without the ongoing injury, lung healing may also occur over time. Multicenter studies with longer follow-up are needed to evaluate the long-term lung health effects of HCT on individuals with SCD.

No relevant conflicts of interest to declare.