Evidence for a Bidirectional Relationship between Cytomegalovirus Replication and acute Graft-versus-Host Disease Nathan Cantoni, Hans H. Hirsch, Nina.

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Evidence for a Bidirectional Relationship between Cytomegalovirus Replication and acute Graft-versus-Host Disease Nathan Cantoni, Hans H. Hirsch, Nina Khanna, Sabine Gerull, Andreas Buser, Christoph Bucher, Jörg Halter, Dominik Heim, André Tichelli, Alois Gratwohl, Martin Stern Biology of Blood and Marrow Transplantation Volume 16, Issue 9, Pages 1309-1314 (September 2010) DOI: 10.1016/j.bbmt.2010.03.020 Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Summary representation of transitions analyzed in time-dependent Cox models. All patients start in the “No CMV/No GVHD” state at day of transplant, and transition to another state on the day they develop CMV replication, or GVHD, or die. Arrows indicate possible transitions: (1) CMV replication in patient without GVHD; (2) CMV replication in patient with GVHD; (3) GVHD occurring in patient without CMV replication; (4) GVHD occurring in patient with CMV replication. Biology of Blood and Marrow Transplantation 2010 16, 1309-1314DOI: (10.1016/j.bbmt.2010.03.020) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Impact of aGVHD on duration and severity of CMV reactivation. Duration of CMV reactivation (A), first antigenemia during CMV replication episode (pp65-positive cells/500,000 cells, B), and maximal CMV antigenemia (pp65-positive cells/500,000 cells, C) in episodes of CMV replication during which GVHD occurred (left bar), episodes of CMV replication that initiated during established GVHD (middle bar), and isolated episodes of CMV occurring in patients without GVHD (right bar). Lines represent medians, boxes interquartile ranges, and whiskers represent ranges. Biology of Blood and Marrow Transplantation 2010 16, 1309-1314DOI: (10.1016/j.bbmt.2010.03.020) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Impact of CMV replication on aGVHD incidence. Forest plots representing the impact of CMV replication on GVHD incidence. Each row represents a separate Cox model. Boxes represent the hazard ratios derived from the Cox model, whiskers the 95% confidence intervals. Hazard ratios were adjusted for patient age, disease, disease stage, donor type, stem cell source, conditioning regimen, degree of HLA match, and type of pharmacological GVHD prophylaxis. Biology of Blood and Marrow Transplantation 2010 16, 1309-1314DOI: (10.1016/j.bbmt.2010.03.020) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Severity and organ distribution of GVHD episodes occurring during CMV replication (black bars) and in the absence of CMV replication (gray bars). Biology of Blood and Marrow Transplantation 2010 16, 1309-1314DOI: (10.1016/j.bbmt.2010.03.020) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions