Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10⁵ units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m² continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 ± 14.2 μmol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 ± 4.5 μmol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 μmol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (<2.8 μmol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.