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The Neuropsychiatric Effects of Treatment with Interleukin-2 and Lymphokine-Activated Killer Cells

KIRK D. DENICOFF, M.D.; DAVID R. RUBINOW, M.D.; MOSHE Z. PAPA, M.D.; COLLEEN SIMPSON, R.N.; CLAUDIA A. SEIPP, R.N.; MICHAEL T. LOTZE, M.D.; ALFRED E. CHANG, M.D.; DONALD ROSENSTEIN, M.D.; and STEVEN A. ROSENBERG, M.D., Ph.D.
[+] Article and Author Information

▸Requests for reprints should be addressed to Kirk D. Denicoff, M.D.; National Institute of Mental Health, Building 10, Room 4C418, 9000 Rockville Pike; Bethesda, MD 20892.


Bethesda, Maryland


Ann Intern Med. 1987;107(3):293-300. doi:10.7326/0003-4819-107-2-293
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Study Objective: To study the neuropsychiatric manifestations of therapy with interleukin-2 and lymphokine-activated killer cells.

Design: Longitudinal survey of consecutive patients who were given the treatment. Each patient was initially interviewed within 5 days before treatment, and a personal and family psychiatric history was obtained during this first session. Cognitive tests and mood self-rating instruments were administered at the beginning and end of interleukin-2 and lymphokine-activated killer cell treatments, before discharge, and at a follow-up visit 2 to 4 weeks after discharge.

Setting: National Cancer Institute inpatient units at the National Institutes of Health.

Patients or Other Participants: Sequential samples of 44 patients with metastatic cancer (age range, 28 to 69 years) who were treated systemically with recombinant interleukin-2 combined with autologous lymphokine-activated killer cells between 30 December 1985 and 31 March 1986.

Measurements and Main Results: Of the 44 patients studied, 15 developed severe behavioral changes that necessitated acute intervention, and 22 patients had severe cognitive changes (all 22 became disoriented and many also had psychometric evidence of cognitive deterioration). The neuropsychiatric side effects were dose and time related, appearing more frequently at the higher dose and almost uniformly at the end of each treatment phase. All 39 patients who were seen at follow-up had a return to their baseline cognitive scores. None of the factors investigated was found to be predictive of the development of neuropsychiatric toxicity.

Conclusions: The development of clinically significant neuropsychiatric changes during the administration of interleukin-2 and lymphokine-activated killer cells was common and may be treatment limiting. A marked latency in the appearance of neuropsychiatric changes after treatment onset was noted in almost all patients. Every patient studied recovered from the neuropsychiatric side effects.

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