Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping by David C. Johnson, Sophie Corthals,

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Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping by David C. Johnson, Sophie Corthals, Christine Ramos, Antje Hoering, Kim Cocks, Nicholas J. Dickens, Jeff Haessler, Harmut Goldschmidt, J. Anthony Child, Sue E. Bell, Graham Jackson, Dalsu Baris, S. Vincent Rajkumar, Faith E. Davies, Brian G. M. Durie, John Crowley, Pieter Sonneveld, Brian Van Ness, and Gareth J. Morgan Blood Volume 112(13):4924-4934 December 15, 2008 ©2008 by American Society of Hematology

Simplified treatment arms of ECOG EA100, Hovon-50, and Myeloma IX studies. David C. Johnson et al. Blood 2008;112:4924-4934 ©2008 by American Society of Hematology

Venn diagram showing overlapping VTE-associated genes between thalidomide Myeloma IX, non-thalidomide Myeloma IX, and thalidomide Hovon-50/ECOG EA100 analyses. Venn diagram showing overlapping VTE-associated genes between thalidomide Myeloma IX, non-thalidomide Myeloma IX, and thalidomide Hovon-50/ECOG EA100 analyses. David C. Johnson et al. Blood 2008;112:4924-4934 ©2008 by American Society of Hematology

Forest plots showing distribution of validated SNPs associated with thalidomide-related VTEs across the Myeloma IX, Hovon-50, and ECOG EA100 trials. Forest plots showing distribution of validated SNPs associated with thalidomide-related VTEs across the Myeloma IX, Hovon-50, and ECOG EA100 trials. Error bars indicate upper and lower 95% CIs. David C. Johnson et al. Blood 2008;112:4924-4934 ©2008 by American Society of Hematology

Predictive tree of thalidomide-related thrombosis in myeloma patients following recursive partitioning analysis. Predictive tree of thalidomide-related thrombosis in myeloma patients following recursive partitioning analysis. David C. Johnson et al. Blood 2008;112:4924-4934 ©2008 by American Society of Hematology

Thalidomide treatment in combination with alkylating agents in myeloma promotes prothrombotic conditions at the endothelium surface via a combination of mechanisms. Thalidomide treatment in combination with alkylating agents in myeloma promotes prothrombotic conditions at the endothelium surface via a combination of mechanisms. Mechanisms include rapid apoptosis of myeloma cells leading to circulating tissue factor (TF), exposed TF by endothelium cells salvaged from apoptosis, increased circulating cytokines (eg, TNFα) with T-cell activation by antigen-presenting cells (APCs), and activated platelets in response to increased circulating cytokines. David C. Johnson et al. Blood 2008;112:4924-4934 ©2008 by American Society of Hematology