The Efficacy of Mesenchymal Stem Cells in Bronchiolitis Obliterans Syndrome after Allogeneic HSCT: A Multicentre Prospective Cohort Study

Background: Bronchiolitis obliterans syndrome (BOS) after allo-HSCT is a devastating complication with limited therapeutic options. We aimed to assess the efficacy and safety of mesenchymal stem cells (MSCs) in BOS after allo-HSCT. Methods: Eighty-one allo-HSCT recipients with BOS diagnosed within 6 months were enrolled in this multicentre prospective cohort study. The choice of prednisone and azithromycin combined with or without MSCs was based on patient preferences (MSC n=49, non-MSC n=32). The primary endpoint was response rate at 3 months, defined as the proportion of patients achieving FEV1 improvement or steroid sparing. Findings: Response rate was 35/49 patients (71%, 95% CI 59 to 84%) and 14/32 (44%, 27 to 61%) in MSC and non-MSC group, respectively (p=0*013). The addition of MSCs was associated with a better difference for change in FEV1 rate of decline, compared to non-MSC group (53 ml/months, 2 to 103; p=0*040). The 3-year overall survival post-diagnosis was 70*6% (55*9 to 85*3%) and 58*2% (36*1 to 78*5%) in MSC and non-MSC group, respectively (p=0*21). Clinical improvement was accompanied by a significant increase of interleukin (IL)-10-producing CD5+B cells. Infections and leukemia relapse were no significant difference between two groups. MSCs were well-tolerated with no serious adverse events. Interpretation: MSCs might be an effective and safe therapy for BOS after allo-HSCT. These data also offer insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials. Our study strengthens evidence for clinical practice of MSC therapy in BOS. Trial Registration: This trial was registered at ClinicalTrials.gov, NCT02543073. Funding Statement: This study was supported by the National Key R&D Program of China (2017YFA105500 and 2017YFA105504), the National Natural Science Foundation of China (81770190 and 81700176), the Health Collaborative Innovation Major Projects of Guangzhou City (201508020254), the Science and Technology Planning Project of Guangdong Province (2014B020226004). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The protocol was approved by institutional review board at each centre. Written informed consents were obtained from all participants in accordance with the Helsinki Declaration.