Adoptive immunotherapy involving bolus-dose recombinant interleukin-2 (rIL-2) has been reported to induce tumor regression in some patients with cancer, but has been associated with severe fluid retention and cardiopulmonary stress. In an effort to preserve the efficacy but reduce the toxicity of this treatment, we used escalating doses of rIL-2 as a constant infusion rather than as a bolus dose. Forty-eight patients with advanced cancer received rIL-2 as a 24-hour infusion in five-day cycles separated by five-day periods of rest and leukapheresis. Eight patients were removed from the study before receiving cells activated in vitro. In the 40 who could be evaluated for their response, there were 13 partial responses (32.5 percent) and 2 minor responses. Partial responses were observed in Hodgkin's disease (one of one), non-Hodgkin's lymphoma (one of one), lung cancer (one of five), ovarian cancer (one of one), parotid cancer (one of two), renal cancer (three of six), and melanoma (five of ten). Responses were associated with a good performance status, a base-line lymphocyte count above 1400 per cubic millimeter, and an rIL-2-induced lymphocyte count of at least 6000. Optimal lymphocytosis required a priming dose of rIL-2 of 3 X 10(6) U per square meter of body-surface area per day, and 15 of 28 patients receiving this priming dose responded to treatment. A weight gain of more than 10 percent of total body weight (five patients) and dyspnea at rest (six patients) were unusual events restricted to patients with poorer pretreatment performance. We conclude that the administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.

The amino acid sequence of a biologically active polypeptide isolated from calf thymus, termed thymosin al, has been determined. Thymosin a, is a heat stable, highly acidic molecule composed of 28 amino acid residues. This peptide is one of several present in thymosin fraction 5 that may participate in the regulation, differentiation, and function of thymus-dependent lymphocytes (T cells). A nomenclature for the family of polypeptides present in thymosin fraction 5 is suggested.

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ower (amplitude) CDS has significant potential to contribute to improved understanding of tumor vascularity and blood flow in vivo. 1 However, its inability to quantitate blood flow is a major current limitation. It was the purpose of this study to devise and test a 2D and 3D a-CDS system designed to quantitate tumor vascularity and flow as they correlate with histologic determinations of vascularity. In addition, changes in flow after intravenous infusion of CM-101 were studied as a means to evaluate possible effects (within 1 h) in tumor blood flow. This exotoxin has been reported to affect tumor vascularity in our previously reported study and was used as a means to produce changes in vascularity that might be detected by 3D a-CDS. This study was designed to evaluate the accuracy of a system to quantitate tumor vascularity with amplitude (power) color Doppler sonography twoand three-dimensionally. The vascularity of 20 transplanted murine tumors was determined with quantitated amplitude color Doppler sonography both two-and three-dimensionally and compared to tumor vascularity estimated by histologic examination. Serial examinations were performed 15, 30, 45, and 60 min after the injection of the exotoxin CM-101 and saline solution to assess changes in tumor vascularity. Three-dimensional amplitude color Doppler sonography best depicted the overall vascularity of tumor when compared to histologic estimation of vessel density. However, neither twonor three-dimensional amplitude color power angiography correlated well to the microvessel count, probably a reflection of the difference in the method for vessel quantification using sonographic versus histologic techniques. Three-dimensional amplitude Doppler sonography correlated better with counts of large vessels (> 100 µm) as opposed to small vessels (> 15 µm). Time-activity curves showed no difference in tumor flow at the times measured in the experimental group injected with CM-101 or when compared to saline solutions in either the peripheral or central portions of the tumor. This three-dimensional amplitude color Doppler sonographic system affords global quantification of tumor vascularity and flow that may, in turn, be useful in determining the probability of malignancy (by determination of branching patterns and vessel regularity) or tumor response or both to treatment. KEY WORDS: Color Doppler sonography; Tumor, vascularity; Vascularity, tumor.

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