Background: Hematopoietic stem cell transplantation (HSCT) remains the only definitive treatment for many benign and malignant hematologic disorders. Despite advances in transplant medicine, HSCT still carries a significant risk of serious complications, including idiopathic pneumonia syndrome (IPS). IPS is characterized by diffuse alveolar injury that is not due to infection or fluid overload. IPS affects 2-17% of patients who have undergone HSCT and has a mortality rate of over 60%. Thus, it is important to identify high-risk patients and develop methods for prevention and early intervention. This study examined the incidence and risk factors of IPS in a national cohort of patients who underwent HSCT in Taiwan.

Methods: This was a retrospective cohort study on patients who underwent hematopoietic stem cell transplantation in Taiwan from January 2009 to February 2019 as documented in the Taiwan Society of Blood and Marrow Transplantation database. To identify possible risk factors for IPS, univariate logistic regression was performed for various demographic and clinical characteristics. Variables with significant between-group differences (p-value < 0.2) were included in the final multivariate Cox proportional hazard model. We plotted Kaplan-Meier survival curves stratified by IPS to examine the impact of IPS on survival. A P-value < 0.05 was deemed significant.

Results: A total of 3,924 patients were included. 43 (1.1%) developed IPS after HSCT. Table 1 shows the characteristics associated with IPS following univariate analysis. Following multivariate analysis, characteristics associated with IPS were total body irradiation (TBI)-based conditioning regimens (HR 2.51; 95% CI, 1.17-5.36; p=0.018) and hyperacute graft vs host disease of the upper GI tract (HR 12.46; 95% CI, 1.68-92.64; p=0.014). 58% of patients who developed IPS after HSCT died within 2 years. The Kaplan-Meier curve (Figure 1) estimates survival in patients with and without IPS. The overall survival probability at two years following stem cell transplantation was 64% in patients without IPS vs 49% in patients with IPS.

Conclusions: In conclusion, while the incidence of IPS was relatively low in this cohort compared to previous studies, IPS was still associated with increased mortality. The strongest independent risk factors for development of IPS after HSCT were conditioning regimens of TBI (which is consistent with recent studies) and hyperacute GVHD of the upper GI tract. Future studies should examine risk factors for IPS in more heterogenous populations.

IMAGE 1: Table 1. Univariate analysis of characteristics between patients with and without idiopathic pneumonia syndrome after HSCT

IMAGE 2: Figure 1. Kaplan-Meier curves showing probability of survival for patients with and without IPS after hematopoietic stem cell transplantation