Increased Programmed Death-1 Molecule Expression in Cytomegalovirus Disease and Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

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Increased Programmed Death-1 Molecule Expression in Cytomegalovirus Disease and Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation Ghislaine M. Gallez-Hawkins, Lia Thao, Joycelynne Palmer, Andrew Dagis, Xiuli Li, Anne E. Franck, Bernard Tegtmeier, Simon F. Lacey, Don J. Diamond, Stephen J. Forman, John A. Zaia Biology of Blood and Marrow Transplantation Volume 15, Issue 7, Pages 872-880 (July 2009) DOI: 10.1016/j.bbmt.2009.03.022 Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 PD-1 expression in CD4+T cells in the CD, PV, and NV groups. A, MFI of PD-1 at indicated time post-HCT for each group. B, Number of CD4+/PD-1+T cells/L at the same time intervals. The median value in each group is shown as a horizontal line. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001 using the Kruskal-Wallis test comparing the 3 groups at each time interval post-HCT. Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 ROC analysis of CD4+/PD-1+ MFI in the NV and PV groups versus the CD group. An MFI scatterplot and ROC curve are shown for each group at day 40 (A) and day 90 post-HCT (B). Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 PD-1 expression in CD8+T cells in the CD, PV, and NV groups. A, MFI of PD-1 at indicated times post-HCT for each group. B, Number of CD8+/PD-1+T cells/L. The median value in each group is shown as a horizontal line.∗P < .05; ∗∗P < .01; ∗∗∗P ≤ .001 using the Kruskal-Wallis test comparing the 3 groups at each time interval post-HCT. Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 ROC analysis of CD8+/PD-1+ MFI in the NV and PV groups versus the CD group. An MFI scatterplot and ROC curve are shown for each group at day 40 (A) and day 90 post-HCT (B). Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 Proportion of subjects with an PD-1 MFI value<200 or>200, controlling for aGVHD grade 0-I and grade II-IV for each CMV group. MFI values > 200 are shown above the axis; values<200 are shown below the axis. Results of a Cochran-Mantel-Haenszel test between the 2 aGVHD groups are shown for CD4+T cells (P=.0009) (A) and for CD8+T cells (P=.01) (B). Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 PD-1 MFI in CD4+ and CD8+T cells of NV subjects with or without GVHD. A and C, MFI for patients with GVHD grade 0-I (designated “no aGVHD”). B and D, MFI for patients with GVHD grade II-IV (designated “aGVHD≥II”). The Mann-Whitney test was used to establish the association between MFI in CD4+/PD-1+T cells and aGVHD grade II-IV (P=.01 at day 40 and .001 at day 90) and between MFI in CD8+/PD-1+T cells and aGVHD II-IV on day 90 post-HCT (P=.01). Biology of Blood and Marrow Transplantation 2009 15, 872-880DOI: (10.1016/j.bbmt.2009.03.022) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions