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

Background:

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (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 multicenter 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. This trial was registered at ClinicalTrials.gov, NCT02543073.

Results:

Response rate was 35/49 patients (71%, 95% confidence intervals [CI] 59 to 84%) (FEV1 improvement n=10, steroid sparing n=25) and 14/32 (44%, 95% CI 27 to 61%) (FEV1 improvement n=3, steroid sparing n=11) in the MSC and non-MSC group, respectively (p=0.013). The adjusted odds ratio of response in the MSC group compared with the non-MSC group was 3.32 (95% CI 1.21-9.11; p=0.02). 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% (95% CI 55.9 to 85.3%) and 58.2% (95% CI 36.1 to 78.5%) in the 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. The incidences of infection and leukemia relapse were no significant difference between two groups. Multiple infusions of MSCs were well-tolerated with no serious adverse events.

Interpretation:

MSCs might be an effective and safe therapy for BOS patients after allo-HSCT. Our study strengthens evidence for clinical practice of MSC therapy in BOS. These data also offer insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials.