The development of a goiter and hypothyroidism in a 28-year-old man in whom metastatic melanoma had been treated with interleukin-2 and lymphokine-activated killer cells (LAK cells) prompted us to assess thyroid function in patients undergoing this therapy. Thirty-four patients with advanced neoplasms who had received interleukin-2 and LAK cells were followed for at least four weeks after treatment. Seven patients (21 percent) had laboratory evidence of hypothyroidism, with a decline in the serum thyroxine concentration to below normal (less than or equal to 35 nmol per liter; normal, 65 to 148), a decline in the serum free thyroxine index, and a rise in the serum thyrotropin concentration (peak values, 7.2 to 166 mU per liter; normal, 0.5 to 5.5) 6 to 11 weeks after treatment. Two patients had elevated serum thyrotropin levels before treatment, which increased further after treatment. In two patients, these abnormal values returned to normal within 10 months. All five symptomatic patients had borderline or elevated serum antimicrosomal antibody titers after treatment; two had serum antibodies to thyroglobulin. Five of the seven patients with hypothyroidism (71 percent) but only 5 of the 27 euthyroid patients (19 percent) had evidence of tumor regression (P less than 0.02). None of 11 patients treated with interleukin-2 but not LAK cells had hypothyroidism. We conclude that treatment with interleukin-2 and LAK cells can cause hypothyroidism, possibly by exacerbating preexisting autoimmune thyroiditis, and that it may be associated with a favorable tumor response.

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Peripheral blood stem cell (PBSC) collection was evaluated in two groups of normal donors who underwent large-volume leukapheresis on a blood cell separator. In Group A (n = 10), a 3-hour leukapheresis was performed. An average of 11.8 L of blood was processed with a mean flow rate of 66 mL per minute and a collection rate of 3 mL per minute. The PBSC product contained a mean 1.4 x 10(10) mononuclear cells (MNCs) (lymphocytes and monocytes), 1.27 x 10(6) colony-forming units-granulocyte-macrophage (CFUs-GM), and an average hematocrit of 4 percent (0.04). Postapheresis blood counts showed significant reductions in MNCs (19%) and platelets (45%) (p less than 0.005). Twenty-four hours later, the MNCs had returned to preapheresis levels. The platelet count returned to baseline only after 7 days. Circulating CFUs-GM remained stable for 3 days after apheresis but were increased twofold by Day 7 after apheresis (p = 0.025). Varying the product hematocrit from 1 percent (0.01) to 13.3 percent (0.13) did not change the number of CFUs-GM collected per MNC. In Group B (n = 4), an average of 18.5 L of blood was processed with a mean flow rate of 94 mL per minute and a collection rate of 3 mL per minute. The PBSC product was collected as four sequential samples and assayed for MNCs and CFUs-GM. Total MNCs averaged 1.7 x 10(10) (an increase of 21% relative to Group A) and CFUs-GM averaged 3.08 x 10(6) (an increase of 143%). Mean MNCs did not vary significantly among the four samples. However, CFUs-GM collected per minute (relative to the first sample) did show 1.26-fold (p = 0.001), 1.86-fold (p = 0.011), and 2.52-fold (p = 0.04) increases in the second, third, and fourth samples. These data suggest that MNCs and committed progenitor cells are recruited during large-volume leukapheresis. Moreover, there is a twofold increase in circulating CFUs-GM 1 week after apheresis.

Using albumin and crystalloid as the only replacement fluids, the effect of partial plasma exchange on the removal and recovery of normal plasma constituents was studied. The results of 30 procedures on 10 individuals were evaluated. Four patterns of removal are described: reduction in the concentration of fibrinogen and C3 were greater than would be expected based upon the extent of the exchange, while IgG, IgM, cholesterol, alkaline phosphatase and SGPT were removed as expected. Reduction of serum glutamicoxalacetic transaminase (SGOT), lactate dehydrogenase (LDH), amylase, and creatine phosphokinase (CPK) averaged 17% less, and uric acid, calcium and K+ averaged 53% less than expected. Concentrations of HCO-3 and glucose did not change. The mean recovery for all constituents except fibrinogen, C3, cholesterol. IgG and IgM was near 100% at 48–72 hr postpheresis. The 72-hr recovery of fibrinogen and complement was 66% and 60%, respectively. Cholesterol recovery was also slow, requiring a minimum of 1 wk to reach prepheresis levels. Measured at a time when quantitative IgM levels were still reduced, alloantibody agglutinating activity (anti-A and anti-B) in a postpheresis sample exceeded prepheresis agglutinating activity. These data demonstrated that, depending upon quantity and frequency of pheresis, partial plasma exchange using albumin replacement may cause progressive marked reduction in concentrations of immunoglobulin, complement, fibrinogen, and cholesterol. Furthermore, newly synthesized antibody may have increased biologic activity.

TRANSFUSION-TRANSMKED CytOI"@OvirUS (TT-CMV) infection was first described in 1966, and since that time its prevention has been the focus of considerable attent i~n . I -~TT-CMV has been documented in a wide variety of clinical circumstances and can be the cause of significant morbidity and mortal it^.^-^ While the incidence of some other transfusion-transmitted viral infections (hepatitis B, hepatitis C, and human immunodeficiency virus) has been significantly reduced by the predonation screening interview and by postdonation serologic testing, TT-CMV cannot be reduced by these measures, because patient history cannot discriminate CMV carriers from noncarriers and antibody screening cannot discriminate infectious units from noninfectious. Eliminating all CMVseropositive donors to prevent TT-CMV would devastate the blood supply, as the prevalence of antibody to CMV ranges from 60 to 80 percent. Thus, traditional practice has by necessity relied upon the use of a small percentage of CMV-seronegative units for a few, select patients. Recent data however, suggest that white cell (WBC) reduction is effective in preventing TT-CMV and therefore may be an easy way to provide "CMV-safe" units to a larger, and rapidly growing, population of patients. In this review, we describe the results of transfusing CMVseronegative blood versus saline-washed, frozen and deglycerolized, and filtered WBC-reduced components, and we discuss the efficacy of these manipulations in reducing TI'-CMV. CMV InfectionHuman CMV is a ubiquitous, DNA-containing herpes virus.7 The risk of CMV infection increases with age, lower socioeconomic status, crowded living conditions, Abbreviations: CMV = cytomegalovirus; E M =enzyme immunopssey; IHA =indirect hemagglutination (essay); LA = passive latex agglutination; RBC(s) = red cell(s); 'IT-CMV = transfusion-transmitted CMV; WBC(s) = white cell(s).

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