title: Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells.
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 (10(5) 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 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 (less than 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.
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000097:blood; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007116:Immunization, Passive / Q000009:adverse effects*; D007167:Immunotherapy / Q000009:adverse effects; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D010205:Pantothenic Acid / Q000097:blood; D012614:Scurvy / Q000097:blood / Q000209:etiology*; D014810:Vitamin E / Q000097:blood
chemical_list: D007376:Interleukin-2; D014810:Vitamin E; D010205:Pantothenic Acid; D001205:Ascorbic Acid