The human T-cell leukemia/lymphoma virus (HTLV) is a novel type-C retrovirus isolated from patients with T-lymphoproliferative malignancies. Thirteen cases of HTLV-associated malignancy from US centers were studied in detail. Ten of these cases share common clinical features and define a typical virus-associated adult T-cell leukemia/lymphoma (ATL). All ten patients presented with Ann Arbor stage IV lymphoma because of skin involvement, bone marrow involvement, or lymphomatous leptomeningitis. Lymphadenopathy occurred in 7 of 10 patients at presentation, and the malignant cells were cytologically pleomorphic. Leukemia occurred in 60% of the patients at presentation. Hypercalcemia was found initially in two-thirds of the patients, with lytic bone lesions or positive bone scans in 7 of 10. Complete remission occurred in 40%, but all have relapsed. These cases closely resemble those virus-positive cases of adult T-cell leukemia/lymphoma (ATL) reported from Japan and the Caribbean. Three additional virus- positive patients had atypical presentations and diagnoses (acute lymphocytic leukemia, Sezary's syndrome, leukemic reticuloendotheliosis), usually with less aggressive clinical courses and atypical demographic and laboratory features. Presence of HTLV serum antibodies in cases of ATL (with hypercalcemia and circulating malignant cells) appears to define a distinct clinicopathologic entity that may occur in geographic clusters.
Small cell lung cancer is distinguished from other lung cancer histologic types by possessing a variety of neuroendocrine properties. Anti-Leu-7 is a monoclonal antibody that recognizes a 110,000-dalton molecular weight glycoprotein initially described on natural killer cells and subsequently reported on a variety of normal and malignant neural and neuroendocrine cell types. We have found intense anti-Leu-7 binding to a large number of small cell lung cancers, while other lung cancer types were negative or showed only weak and focal binding. Other antigens expressed by natural killer cells, lymphocytes, and monocytes were never or less often expressed on small cell lung cancer cells. In addition, we report for the first time anti-Leu-7 binding by carcinoids, carotid body tumors, pheochromocytomas, endocrine cells of the fetal bronchus and the adult intestine, and select pancreatic islet cells. Anti-Leu-7 binding by small cell lung cancer is consistent with a derivation from pulmonary precursor cells, and anti-Leu-7 staining is clinically useful for the identification of human neuroendocrine tumors of the amine precursor uptake and decarboxylation (“APUD”) type.
The radiolabeled anti-T cell antibody T101 can be used for specific tumor localization, but unlabeled T101 produces limited cytotoxicity in patients. We thus studied the in vitro cytotoxic effects of T101 labeled with 125I, a radionuclide known for its short-range, high- linear-energy electrons. We showed that 125I-T101 could be readily prepared at high specific activity with high immunoreactivity. Human malignant T cell lines HUT 102, MOLT-4, and HUT 78 were found to differ in the number of T65 determinants (the antigen recognized by T101) and the sensitivity to external x-ray radiation, which were of significance for the cytotoxicity of 125I-T101 in vitro. The cytotoxic effects of 125I-T101 were also found to be dose dependent and increased with exposure time under frozen conditions. As controls, unlabeled T101 had no cytotoxic effect, while free Na 125I or the 125I-labeled irrelevant antibody 9.2.27 exerted minor cytotoxicity. In HUT 102 and MOLT-4, more than 3 logs' cell killing was achieved within four weeks. Because considerable cytotoxicity was demonstrated in vitro by 125I-T101 on T65- positive malignant cells, and because low-dose 111In-T101 can be used successfully for tumor localization, future trials using 125I-T101 at high specific radioactivity may improve therapeutic results in patients with T65-positive malignancies.
DNA content analysis by flow cytometry was performed in 32 patients with plasma cell myeloma and 3 patients with Waldenstrom's macroglobulinemia to determine the biologic and potential clinical usefulness of this technique. Hyperdiploid tumor DNA content was found in 23 myeloma patients (72%) during the course of illness, including 16/28 at presentation, but in none of 3 patients with Waldenstrom's macroglobulinemia. There was no significant association of aneuploidy in myeloma patients with age, sex, race, or M-protein class. Myeloma patients with aneuploid tumor cells were more likely to have advanced stage (p = 0.032) than patients with diploid plasma cells, and all patients with renal failure had aneuploid tumors. Pretreatment factors significantly associated with survival included stage (p = 0.01), serum creatinine (p = 0.003), and tumor DNA content (p = 0.005). Multivariate analysis using the Cox life table regression procedure indicated that the significant relation of tumor DNA content with survival remained after adjusting for stage (p less than 0.005). Myeloma patients with diploid tumors at diagnosis frequently had aneuploid plasma cells at the time of relapse, indicating a possible relationship of chromosomal alterations in the tumor to clinical drug resistance. We conclude that aneuploid tumor cells at the time of diagnosis of myeloma are of independent prognostic significance, and the development of aneuploidy is a frequent occurrence at clinical relapse, suggesting the change in DNA content are of biologic and clinical significance.
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