Analysis of cardiac-specific toxicity. (A) Pathologic and immunohistochemical analysis of myocardium from both patients. Hematoxylin and eosin (H&E) stained sections of myocardium shown at two magnifications for each patient (top panels), demonstrating lymphocytic infiltrate and diffuse myocyte necrosis. Immunohistochemical (IHC) staining with anti-CD3 (lower panels) demonstrates that lymphocytic infiltrates are T cells, shown at two magnifications. (B) Cytokines in the peripheral blood and the pericardial fluid in Case 2 obtained post mortem show evidence of T-cell activation. Thirty cytokines were assayed; each cytokine level shown is normalized to the concentration of that cytokine in a peripheral blood sample obtained at baseline. The patient was given injections of filgrastim (G-CSF) as per standard of care post-ASCT. Baseline levels of cytokines in blood were VEGF, 1.73 pg/mL; IL-1β, 0.5 pg/mL; G-CSF, 10.51 pg/mL; epidermal growth factor (EGF), 23.13 pg/mL; IL-10, 2.54 pg/mL; HGF, 357.83 pg/mL; FGF-basic, 4.45 pg/mL; IFN-α, 70.76 pg/mL; IL-6, 3.42 pg/mL; IL-12, 93.34 pg/mL; regulated upon activation, normal T-cell expressed and secreted (RANTES), 12 717 pg/mL; eotaxin, 76.1 pg/mL; IL-13, 0.53 pg/mL; IL-15, 59.94 pg/mL; IL-17, 0.16 pg/mL; macrophage inflammatory protein 1 alpha (MIP-1α/CCL3), 14.85 pg/mL; GM-CSF, 0.77 pg/mL; MIP-1β, 36.44 pg/mL; MCP-1, 953 pg/mL; IL-5, 0.34 pg/mL; IFN-γ, 2.49 pg/mL; tumor necrosis factor alpha (TNF-α), 1.26 pg/mL; IL-1Rα, 37.66 pg/mL; IL-2, 0.56 pg/mL; IL-7, 15.36 pg/mL; IP-10, 23.14 pg/mL; IL-2R, 205.81 pg/mL; MIg, 10.51 pg/mL; IL-4, 9.91 pg/mL; and IL-8, 10.68 pg/mL.