Retrospective Analysis of Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation

Objective: To explore the incidence, clinical features,risk factors and survival prognosis of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by using large samples form a single center.Provide a prerequisite for improving the early diagnosis of BOS after allo-HSCT.

Methods: We retrospectively investigated the case data of 802 patients who underwent allo-HSCT in our institute in petiod of January 1, 2015 to December 31, 2019 and survived more than 100 days. Adopt a multidisciplinary discussion method in the Department of Hematology, Respiratory and Radiology,according to the 2014 National Institutes of Health (NIH) ,diagnose and assess the severity of patiencts with BOS.Describe the clinical characteristics of BOS, and then analyze the risk factors and survival prognosis.

Result: Among the 802 patients，46 patients（5.74%), 26males and 20 females with a median age of 32 years was diagnosed BOS.The median time to first appearance of respiratory symptoms was 13.5 months after transplantation, and the median time to diagnosis was 14.4 months.The cumulative incidence rate for 1- year, 2- year, and 5 -year after allo-HSCT is 3.7%, 6.5%, and 8.4%,while the cumulative incidence rate for patients already diagnosed with cGVHD is 7.5%、12.4% and 15.0% . Univariate analysis showed several risk factors associated with the onset of BOS,including the presence of preoperative or postoperative pneumonia,free of ATG ,use of DLI,peripheral blood stem cell transplantation, occurrence of GVHD and the severity and number of these episodes .And multivariate analysis denotes :free of ATG ,use of DLI,and number of organs affected by cGVHD were the variables correlated with increased incidences of BOS. At the onset of BOS, FEV1, FEV1%pred, FEV1/FVC ,FEV1/FVC %pred were significantly lower than those before transplantation. Compare before and after onset, the average decrease rate of FEV1 is 0.17L/month, while FEV1%pred is 5.15%/month.We also recorded the last follow-up lung function to evaluate the treatment efficacy : after treatment, the average FEV1 was 2.46L, the average of FEV1%pred was 36.61%, the average of FEV1/FVC was 45.80%, and the average of FEV1/FVC%pred was 56.36%, before and after treatment., FEV1%pred has no statistical difference (P=0.455).Not only that, there was no statistical difference in the treatment effect among different severity of BOS.The median follow-up time after the diagnosis of BOS was 19 months, and there was no statistical difference in the survival rate between the BOS and non-BOS groups at the end of the follow-up. The analysis result shows that early-onset BOS is a independent risk factors for poor survival time of BOS.Compare BOS with other non-infectious lung complications,the severity of BOS and cGVHD involving extrapulmonary organs are statistically different.

Conclusion: BOS is a serious refractory complication after allo-HSCT.Early detection of potential patients with BOS is very difficult , and because most of the BOS patients did not respond to the therapy well, eventually lead to the irreversibility of deterioration of PFT. Compared with other non-infectious lung complications, strong association with severe cGVHD and deterioration of lung function characterized by obstructive ventilation disorder，etc.It suggests that the clinical need to deepen the recognition of BOS, continue to explore the early diagnosis method of BOS , more importantly , strive to give effective treatment at the early stage to improve the prognosis.

KEYWORDS Bronchiolitis obliterans Allogeneic hematopoietic stem cell transplantation Risk factors Non-infectious pulmonary complications