The use of interleukin 2 (IL-2), either alone or in combination with lymphokine activated killer-cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma who died after receiving IL-2 based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death, unrelated to the presence of metastatic tumor, was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: 2 patients with acute myocardial infarction, one with and one without significant coronary artery disease; 2 cases of unexplained lymphocytic myocarditis; and 1 case of fatal pulmonary capillary plugging following an infusion of LAK cells. Thus, not unlike other forms of therapy for cancer, IL-2 based immunotherapy does not appear to be without significant toxicity.
