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Background. The median survival for adults with glioblastoma multiforme (GBM) is 12 months, despite surgery, radiation, and chemotherapy. Regimens using interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cells have been beneficial against systemic cancers, albeit with significant toxicity. Methods. Nineteen adults with recurrent malignant glioma (5 GBMs, and 4 anaplastic astrocytomas (AA)), Karnofsky performance status 60 or greater, were treated with intracavitary autologous LAK cells plus IL-2 after reoperation. Lymphokine-activated killer cells and IL-2 were given on day 1, and IL-2 alone was given 5 times during a 2-week cycle. This cycle was repeated at 2 weeks to constitute one 6-week course of therapy. Each two-cycle course of treatment was repeated at 3-month intervals for patients with stable disease or response to therapy. At the conclusion of immunotherapy, all patients were offered chemotherapy, generally carmustine or procarbazine, including responders. Corticosteroids were strictly limited during immunotherapy. Sequential reservoir aspirates were obtained for microbiologic and cytologic analyses. Results. The maximal tolerated dose for a 12-dose course of therapy was 1.2 million international units (MIU) per dose. Dose-limiting, cumulative IL-2-related central nervous system (CNS) toxicity was observed at 2.4 MIU per dose. Three responses were confirmed by computed tomography scan during therapy: one complete response (CR) (1 AA), and two partial responses (PR) (2 GBM); as well as a significant increase in GBM survival. One additional CR (GBM) was observed at 17 months. The median survival for immunotherapy patients with GBM was 53 weeks after reoperation (N = 15) (mean, 87.9 [+ or -] 21.4 weeks, standard error for the mean), with 8 of 15 surviving more than 1 year (53%). The median survival for 18 contemporary patients with GBM reoperated and treated with chemotherapy was 25.5 weeks (mean, 27.4 [+ or -] 3.7 weeks), with 1/18 alive at 1 year (>6%). Six of the 15 patients with GBM had additional surgery or biopsy, and chemotherapy after immunotherapy. The contribution of subsequent chemotherapy to survival cannot be discounted. Conclusions. Lymphokine-activated killer cells and IL-2 can be administered safely within the CNS resulting in improved long term survival in patients with recurrent glioblastoma. Increased survival was associated with significant biologic changes characterized by a regional eosinophilia, and extensive lymphocytic infiltration. A prospective randomized clinical trial is warranted. Cancer 1995; 76:840-52. Key words: interleukin-2, lymphokine-activated killer cells, glioma, glioblastoma, astrocytoma, brain, immunotherapy, eosinophil, survival, biologic response modifiers.

We used quantitative autoradiography (QAR) to evaluate the effect of systemically administered dexamethasone on capillary permeability in brain tumors and surrounding brain. Rats bearing unilateral right hemispheric C6 gliomas were studied at one and twelve hours after 10 mg/kg of intraperitoneal dexamethasone. Capillary permeability was determined by measuring unidirectional blood-to-brain and blood-to-tumor transport of 14C-alpha aminoisobutyric acid (14C-AIB) over fifteen minutes. 14C-AIB entry into tumor, brain adjacent-to-tumor (BAT), and ipsilateral and contralateral cortices was determined and expressed as a unidirectional transfer constant, K. Nontreated tumor K was more than two-fold greater than K for BAT and ten-fold greater than ipsilateral cortical K, confirming substantial barrier disruption in tumor. In addition, the K for BAT was also significantly greater than K for cortex, indicating that the barrier in the peritumoral region was also disrupted. One hour after dexamethasone treatment, tumor K fell to 63% of its pretreatment value (p < 0.025). By twelve hours post-treatment, tumor K fell to 25% of the untreated value (p < 0.001) and to 47% of the one-hour value (p < 0.005). BAT K fell to 29% of its untreated value (p < 0.02) and to 46% of its one-hour value (p < 0.02). By 12 hours, ipsilateral cortical K fell to 67% of the untreated cortical value (p < 0.05). Compared to untreated values, there was no significant difference between contralateral cortical K at either one or twelve hours. Capillary permeability of both C6 brain tumor and normal brain vessels around tumor are increased as measured by blood-to-tissue transport of 14C-AIB. A single dose of dexamethasone reduces capillary permeability as early as one hour after administration in the tumor, then continuously over a twelve-hour time course in both tumor and BAT.

THE ASSOCIATION of bacterial meningitis with a retroperitoneal abscess is uncommon. There have been only four cases in the literature of meningitis caused by dissemination of a psoas abscess.1,2 Recently, we observed a patient with pneumococcal meningitis in whom a pneumococcal psoas abscess subsequently developed as an iatrogenic complication of a lumbar puncture.Report of a CaseA 50-year-old man was admitted to the New York (Manhattan) Veterans Administration Medical Center for evaluation of fever, confusion, and lower back pain.The patient had been in good health until two weeks before admission, when he noted the onset of lower back pain without fever, abdominal pain, leg weakness, or incontinence of bowel or bladder. During the week before hospitalization, the patient visited two outpatient medical clinics for evaluation. He claimed that spinal roentgenograms were obtained and interpreted as normal. Bed rest and analgesics were prescribed both times. Two days before