Risk Factors for the Development of Non-Infectious Pulmonary Complications Post-Hematopoietic Cell Transplantation in Sickle Cell Disease

Introduction HCT for SCD is associated with pulmonary complications with significant morbidity and mortality. There is an important knowledge gap in the understanding of the predictive factors for non-infectious pulmonary complications post-HCT. This study aims to assess the impact of various transplant-related risk factors on pulmonary complications post-HCT in patients who underwent transplants between 1990 to 2022 in the US. Methods We queried the HCT for SCD de-identified dataset obtained through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BIOLINCC) of patients undergoing HCT between 1990-2022 which were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. Transplant Essential Data was submitted for all patients. A subset of centers was assigned to the Comprehensive Report Form (CRF) track and submitted SCD-specific data including details on non-infectious pulmonary complications of Interstitial pneumonitis (Ipn), Acute respiratory distress syndrome (ARDS) or Idiopathic pneumonia syndrome (IPS), their treatment requiring intubation or mechanical ventilation. The risk factors of these outcomes were analyzed using univariable and multivariable logistic regression model, which was built using backward AIC selection procedures. Results Of 1718 patients undergoing HCT for SCD, 766 patients had CRFs submitted for Ipn/ARDS/IPS. 39 (5.1%) developed Ipn/ARDS/IPS and 99 patients (13%) required intubation or mechanical ventilation. In multivariable logistic regression, Sß-thalassemia genotype (OR:3.66, p=0.016), transplant before 2013 (OR:4.72, p=0.006), HLA mismatch relative (OR: 2.93, p=0.016) and matched unrelated donor (OR: 2.95, p=0.013) showed an increased risk for Ipn/ARDS/IPS. An increased risk for intubation or mechanical ventilation was seen in patients with HCT before 2013 (OR:3.49, p=0.004), HLA mismatch relative (OR:2.38, p=0.008), matched unrelated donor (OR:1.87, p= 0.059), graft failure (OR:1.95, p= 0.014), AGVHD (OR:4.50, p=<0.0001), and TMA post-HCT (OR:6.23, p=<0.0001). Of 725 patients on whom CRFs were available on the occurrence of other non-infectious pulmonary complications, 47 (6.48%) developedthese abnormalities post-HCT. The risks were increased with AGVHD (OR:2.91, p=0.003) and h/o ACS pre-HCT (OR:2.87, p=0.018). The use of ATG (OR:0.33, p=0.025) was a protective factor. Conclusions Non-infectious pulmonary complications of HCT for SCD are associated with disease-related factors such as the genotype, history of ACS in the two years prior to HCT; transplant-related factors such as donor type, year of transplant, use of ATG; and post-HCT complications such as AGVHD, GF, and TMA. Further study of pulmonary complications and their prediction can inform shared decision-making and help in better management and prevention of these complications.