Patterns of B Cell Activating Factor (BAFF) Levels, B Cell Recovery, and BAFF/B Cell Ratios Correlate with the Development of Chronic Graft-Versus-Host Disease (cGVHD) Following Hematopoietic Stem Cell Transplantation (HSCT)

There is evidence that B cells play a role in the development of chronic graft-versus-host disease (cGVHD), a major cause of non-relapse morbidity and mortality following hematopoeitic stem cell transplantation (HSCT). Elevated levels of B cell activating factor (BAFF) relative to the number of circulating B cells have been associated with the development of cGVHD as well as its response to treatment. To better define the relationship between BAFF levels, the recovery of CD19 B cells, and BAFF/CD19 B cell ratios and cGVHD following HSCT, we prospectively analyzed 440 hematologic malignancy patients who underwent HSCT. Two hundred and fifty four patients (58%) underwent a reduced intensity HSCT; 375 (85%) received filgrastim-mobilized peripheral blood stem cells. Sixty-one percent developed cGVHD, with a median time to development of cGVHD of 221.5 days. Whole blood and plasma samples were collected at 1, 3, 6, and 12 months after HSCT and analyzed by flow cytometry and enzyme linked immunosorbent assay for CD19 B cells and BAFF levels respectively. Results in patients who developed cGVHD were compared to patients who did not develop cGVHD. At 1 month after HSCT, BAFF levels were significantly higher in the no cGVHD cohort compared to the cGVHD cohort (14.78 versus 11.31ng/ml, p=0.003)(see figure below). BAFF levels gradually fell in the no cGVHD cohort while remaining stable in the cGVHD cohort such that they were significantly lower in the no cGVHD cohort by 12 months after HSCT (5.63 versus 9.11ng/ml, p=0.018). In contrast, CD19 B cell count was similar between the two cohorts through 6 months after which point it was higher in the no cGVHD cohort (279.0 versus 119.0 cells/μL at 12 months, p=0.062). This correlated to a significantly decreased BAFF/CD19 B cell ratio in this cohort at 12 months after HSCT (0.03 versus 0.15, p=0.01). Prednisone is known to lower BAFF levels so each cohort was further analyzed based on the concurrent use of prednisone at the time of sample collection. BAFF levels were lower in patients who received prednisone at the time of analysis. BAFF levels fell sharply in both the cGVHD and no cGVHD cohorts on prednisone between 1 and 3 months after HSCT such that there was no significant difference between the two groups. However, within the group of patients who received prednisone at 3 months, patients who did not develop cGVHD had a significantly higher CD19 B cell count at this time than those who subsequently developed cGVHD (88.0 versus 20.5 cells/μL, p=0.037). These results suggest that patients who do not develop cGVHD achieve higher BAFF levels early after HSCT followed by more rapid B cell recovery, which in turn results in the normalization of BAFF levels and BAFF/CD19 B cell ratios. In contrast, B cell recovery is delayed and high BAFF/CD19 B cell ratios persist in patients who develop cGVHD.