High donor regulatory B cells (Bregs) and their rapid recovery are associated with protection from the development of acute graft‐versus‐host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation

Summary This study aimed to evaluate the peripheral blood donor CD19 + CD24 hi CD38 hi regulatory B‐cell (Breg) content and the Breg recovery rates during 90 days following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and their correlation with the development of acute graft‐versus‐host disease (aGVHD). Twenty‐four donor–recipient pairs with hematological malignancies who underwent unmanipulated, fully HLA‐matched allo‐HSCT from related siblings were enrolled. The frequency of Bregs and their absolute number were significantly lower in donors whose recipients developed aGVHD (* p = 0.005 and * p = 0.016, respectively). Acute GVHD (+) patients had a significantly diminished percentages of Bregs recovered at days 60 and 90 compared to the aGVHD (−) ones (* p < 0.001 and * p = 0.002, respectively). A median donor Breg <1.85 as well as median Breg <1.92, <1.45, and <1.36 recovered on days 30, 60, and 90 were associated with a greater cumulative incidence of aGVHD (* p = 0.036, * p = 0.004 and * p = 0.006, respectively). Multivariate analysis revealed that infusion of grafts with a median Breg >1.85% decreased the risk of grades II–IV aGVHD (hazard ratio (HR) = 0.033, 95% confidence interval [CI] = 0.002–0.477; * p = 0.012). Our results revealed, for the first time, that high donor Breg content and their rapid recovery within 90 days after allo‐HSCT were associated with a decreased risk of aGVHD.