Post-Transplantation B Cell Activating Factor and B Cell Recovery before Onset of Chronic Graft-versus-Host Disease Caron A. Jacobson, Lixian Sun, Haesook.

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Post-Transplantation B Cell Activating Factor and B Cell Recovery before Onset of Chronic Graft-versus-Host Disease Caron A. Jacobson, Lixian Sun, Haesook T. Kim, Sean M. McDonough, Carol G. Reynolds, Michael Schowalter, John Koreth, Corey S. Cutler, Vincent T. Ho, Edwin P. Alyea, Philippe Armand, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz, Stefanie Sarantopoulos Biology of Blood and Marrow Transplantation Volume 20, Issue 5, Pages 668-675 (May 2014) DOI: 10.1016/j.bbmt.2014.01.021 Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 BAFF levels and B cell recovery after allogeneic HSCT. Patients who received either MAC or RIC are shown separately according to subsequent development of cGVHD. (A) BAFF levels (squares) and B cell numbers (triangles) after MAC in patients in the no cGVHD cohort. (B) BAFF levels (squares) and B cell numbers (triangles) after MAC in patients in the cGVHD cohort. (C) BAFF levels (squares) and B cell numbers (triangles) after RIC in patients in the no cGVHD cohort. (D) BAFF levels (squares) and B cell numbers (triangles) after RIC in patients in the cGVHD cohort. *Statistically significant differences (P < .05). Note that blood samples obtained after the clinical onset of cGVHD were excluded from the analysis. Biology of Blood and Marrow Transplantation 2014 20, 668-675DOI: (10.1016/j.bbmt.2014.01.021) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Patterns of BAFF levels, B cell numbers, and BAFF/B cell ratios after HSCT before development of cGVHD. Serial values during the first year after HSCT for patients who received either MAC (A, C, and E) or RIC (B, D, and F) before HSCT. Patients who developed cGVHD (triangles) are compared with those who did not develop cGVHD (squares). *Statistically significant difference (P < .05). Median values for those that were significantly different after MAC were as follows: 6 months: cGVHD, 9.79 ng/mL (range, 0.62 to 58.43 ng/mL) versus no cGVHD, 5.71 ng/mL (range, 0.08 to 34.49 ng/mL), P = .025; 9 months: cGVHD, 12.3 ng/mL (range, 1.75 to 37.38 ng/mL) versus no cGVHD, 3.99 ng/mL (range, 0.83 to 31.82 ng/mL), P = .004; 12 months: cGVHD, 8.68 ng/mL (range, 2.37 to 22.17 ng/mL) versus no cGVHD, 4.3 ng/mL (range, 3.48 to 25.3 ng/mL), P = .02. Median values for those that were significantly different after RIC are as follows: 6 months: cGVHD, 7.09 ng/mL (range, 0 to 26.01 ng/mL) versus no cGVHD, 9.92 ng/mL (range, 0 to 80.49 ng/mL); P = .05. Significant differences in median total B cell numbers were seen at 3 months after MAC: cGVHD, 10 cells/μL (range, 0 to 631.41 cells/μL) versus no cGVHD, 37 cells/μL (range, 0 to 434.64 cells/μL); P = .008. BAFF/B cell ratios were calculated as described previously and are depicted on a log scale. A significant difference in median values was seen at 3 months after MAC: cGVHD, 1.11 (range, 0.05 to 20.07) versus no cGVHD, 0.37 (range, 0.03 to 10.75); P = .01. Biology of Blood and Marrow Transplantation 2014 20, 668-675DOI: (10.1016/j.bbmt.2014.01.021) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Changes in BAFF levels and B cell recovery in patients receiving sirolimus for GVHD prophylaxis after HSCT. Serial median BAFF levels (left y-axis, squares) are compared with B cell numbers (right y-axis, triangles) in patients at 1, 3, 6, 9, and 12 months post-transplantation. (A) Patients who received sirolimus after HSCT. (B) Patients who did not receive sirolimus after HSCT. Note: All patients studied after HSCT and before cGVHD onset were combined in this analysis. Biology of Blood and Marrow Transplantation 2014 20, 668-675DOI: (10.1016/j.bbmt.2014.01.021) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions