Toxicity kinetics and clinical potential of subarachnoid lymphocyte infusions

The feasibility of intrathecal lymphocyte infusions was examined since patients with gliomas are known to have circulating, tumor-specific, cytotoxic lymphocytes. Human (xenogenic) and syngenic lymphocytes were infused intrathecally into rabbits, and the toxicity and kinetics of the infused cells evaluated. Cerebrospinal fluid cell counts rose to as high as 70,000 lymphocytes/cu mm 12 hours after infusion and then dropped logarithmically over several days. No infiltration of host cells into the subarachnoid space in response to the lymphocyte infusions was detected. Evidence is presented that intrathecally infused lymphocytes may escape into the systemic circulation. Toxicity was minimal, especially following syngenic intrathecal lymphocyte infusions. A systemic allergic response, characterized by choroid plexitis and pulmonary edema was noted following a second xenogenic but not after a second or even a third syngenic lymphocyte infusion.