Sezary's syndrome is a leukemic proliferation of OKT4+ lymphocytes. Sezary cells were isolated by differential centrifugation and fused to CEM.8azar.C, and HGPRTase-lacking clone of CEM. The hybrid cells were studied for their ability to produce soluble mediators of human monocyte cytotoxicity. The product of a single clone, FtF3, which bore the surface phenotype of Sezary cells, was characterized. Monocyte cytotoxicity-inducing factor (MCF) was found to be stable at pH 2 for 1 hr, unlike IFN-gamma, and was found to be more heat stable as well. Moreover, treatment of MCF with antisera to IFN-gamma, IFN-alpha or a combination of IFN-gamma and IFN-alpha failed to neutralize its biologic activity. MCF binds to matrix gel Red A. MCF eluted from this dye-ligand was found to have an apparent m.w. of 11,500 by gel filtration and 14,700 by SDS-polyacrylamide gel electrophoresis. MCF produced by hybridized Sezary cells appear to be neither IFN-gamma nor an altered molecular form of IFN-gamma, yet is a potent inducer of human monocyte cytotoxicity.
22 Background: End-of-life anti-neoplastic treatment does not improve quality of life nor prolong survival of advanced cancer patients. It is also not cost-effective. To-date, there has been little data examining real-world patterns of chemotherapy and immunotherapy treatment at end of life. We investigated use of chemotherapy and/or immunotherapy in the last 14 days of life across a community oncology network of 5 practices, 100 sites of care, and 160 oncology providers. Methods: Using a real-time, network-wide database, we identified patients with solid tumor malignancies who died during an episode of active treatment, defined as having received intravenous (IV) chemotherapy and/or immunotherapy within 90 days of death. We then identified patients in this cohort who received IV chemotherapy and/or IV immunotherapy within 14 days of death (TxEoL). We studied TxEoL patterns by cancer type, treatment type, line of therapy, patient age, patient race, and oncology provider years in practice. Statistical significance was assessed using Pearson’s Chi-squared test. Results: 2,858 qualifying solid tumor cancer patients with dates of death between 1/1/2019 and 5/31/2020 were identified. Observed rates of TxEoL were 16.7% for immunotherapy alone vs. 19.6% for chemotherapy +/- immunotherapy (p = 0.09). We found high variation in TxEoL across 132 oncologists that had 5 or more deceased patients (range: 0% to 50%, mean: 19.2%, median: 19.6%). We found no association of TxEOL with physician years in practice, patient age or race. Rates of TxEoL in the first-line setting were significantly higher than in second-line setting or later (23.3% versus 16.4%, p < 0.01). Patients with head and neck, pancreatic, and hepatobiliary malignancies were the most likely to receive TxEoL, while patients with prostate, brain, and ovarian malignancies were the least likely to receive TxEoL. Conclusions: Our data and method identified wide variation in TxEoL patterns across a large community oncology network, suggesting room for provider-level interventions to improve treatment decisions in patients at high risk of death. Studies within our group, such as examining the impact of palliative care referrals on IV anti-cancer treatment in patients potentially facing end of life, are ongoing.
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