Hemodynamic effects of the administration of tumor-infiltrating lymphocytes to cancer patients

Abstract

Tumor-infiltrating lymphocytes (TILs) can mediate tumor regression in selected patients with advanced cancer. To study some of the physiological changes associated with TIL administration, hemodynamic effects were measured while 2 x 10(10) to 20 x 10(10) TILs (mean 10 +/- 1 x 10(10)) were infused into 22 patients. In 10 patients, the first bag of TILs was administered without any interleukin-2 (IL-2) in the infusion bag; subsequent bags in the same patients and all bags in the next 12 patients contained IL-2 in low concentrations (300,000 IU). Two hours following infusion (as compared with baseline), patients developed tachycardia (110 +/- 3.3 vs. 76 +/- 3.5 beats/min; p < 0.001), increased cardiac index (4.9 +/- 0.2 vs. 3.2 +/- 0.13 L/min/m2; p < 0.001), decreased systemic vascular resistance (677 +/- 37 vs. 1185 +/- 63 dyn/s/cm5; p < 0.001), and increased pulmonary artery diastolic pressure (15.9 +/- 1.4 vs. 10.6 +/- 1.1 mm Hg; p = 0.002). No significant changes in systemic blood pressure were noted. Analysis of data obtained in the 10 patients after infusion of the first bag of TILs (4.5 +/- 0.4 x 10(10)) without IL-2 present in the infusate revealed similar, though less severe, changes. No significant correlation was noted between in vitro production of tumor necrosis factor-alpha, interferon-gamma, and granulocyte-macrophage colony-stimulating factor by TILs and hemodynamic effects when administered to patients. These results indicate that TIL infusion can cause hemodynamic changes similar to those previously reported in patients undergoing IL-2 therapy.