Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells

S. L. Marcus, Elisabeth M. Paietta, E. Paietta, N. Ciobanu, J. Strauman, P. H. Wiernik, S. H. Hutner, O. Frank, H. Baker

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Abstract

Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (105 units/kg every 8 h) interleukin 2, (b) 6 1/2 days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering on the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 ± 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 ± 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (< 0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.

Original languageEnglish (US)
Pages (from-to)4208-4212
Number of pages5
JournalCancer Research
Volume47
Issue number15
StatePublished - 1987

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Adoptive Immunotherapy
Lymphokine-Activated Killer Cells
Interleukin-2
Ascorbic Acid
Therapeutics
Scurvy
Leukapheresis
Chills
Urine Specimen Collection
National Cancer Institute (U.S.)
Vitamin E
Renal Cell Carcinoma
Tachycardia
Cellular Immunity
Hypotension
Vomiting
Diarrhea
Melanoma
Colon
Fever

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Marcus, S. L., Paietta, E. M., Paietta, E., Ciobanu, N., Strauman, J., Wiernik, P. H., ... Baker, H. (1987). Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. Cancer Research, 47(15), 4208-4212.

Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. / Marcus, S. L.; Paietta, Elisabeth M.; Paietta, E.; Ciobanu, N.; Strauman, J.; Wiernik, P. H.; Hutner, S. H.; Frank, O.; Baker, H.

In: Cancer Research, Vol. 47, No. 15, 1987, p. 4208-4212.

Research output: Contribution to journalArticle

Marcus, SL, Paietta, EM, Paietta, E, Ciobanu, N, Strauman, J, Wiernik, PH, Hutner, SH, Frank, O & Baker, H 1987, 'Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells', Cancer Research, vol. 47, no. 15, pp. 4208-4212.
Marcus, S. L. ; Paietta, Elisabeth M. ; Paietta, E. ; Ciobanu, N. ; Strauman, J. ; Wiernik, P. H. ; Hutner, S. H. ; Frank, O. ; Baker, H. / Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. In: Cancer Research. 1987 ; Vol. 47, No. 15. pp. 4208-4212.
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AU - Ciobanu, N.

AU - Strauman, J.

AU - Wiernik, P. H.

AU - Hutner, S. H.

AU - Frank, O.

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N2 - Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (105 units/kg every 8 h) interleukin 2, (b) 6 1/2 days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering on the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 ± 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 ± 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (< 0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.

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