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Background: Interleukin-2 (IL-2) is used in the treatment of solid tumors and hematologic malignancies. Sudden death is a rare complication of IL-2 treatment., Methods: A patient with lymphoma underwent chemoradiotherapy myeloablation and autologous stem cell transplantation. The stem cells were cultured in IL-2 (6000 IU/mL) for 24 hours prior to infusion. After engraftment, treatment with IL-2 (1.8 x 10(6) IU/m2/day administered subcutaneously) was begun. After 4 days of treatment, the patient suddenly died. An autopsy was performed., Results: Histologic examination of the myocardium revealed a diffuse, lymphocytic infiltrate with scattered, multinucleated giant cells and foci of myocardial degeneration consistent with giant cell myocarditis. The lymphocytes were predominantly CD4 positive T cells, and the majority of these cells stained with antibodies for perforin, suggesting an unusual cytolytic role for these lymphocytes. DNA end-labeling of myocardial tissue sections revealed numerous apoptotic myocytes within the lymphocytic infiltrate., Conclusions: To the authors' knowledge, this is the first report of giant cell myocarditis in association with high dose chemotherapy, transplantation, and IL-2 immunomodulation. The authors suggest that the cytokine imbalance produced by IL-2 may have initiated a preferential activation of T helper cells and an autoimmune phenomenon manifesting as giant cell myocarditis.