chiniofon and Hodgkin-Disease

Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.

Topics: Adolescent; Adult; Aged; Antigens, Differentiation, T-Lymphocyte; CD4-Positive T-Lymphocytes; CD8 Antigens; Female; Hodgkin Disease; Humans; Hydroxyquinolines; Indium Radioisotopes; Lymphocyte Depletion; Male; Metabolic Clearance Rate; Middle Aged; Organometallic Compounds; Oxyquinoline; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Following indium-111 oxine-labelled autologous lymphocyte infusion, 39 lymphocyte scintigraphies were performed in 35 patients with Hodgkin's disease (HD). Lymphocytes were obtained after leukapheresis and Lymphoprep gradient centrifugation and were further purified by an adherence step to eliminate monocytes. A median of 1.2 (0.2-3.7) X 10(9) cells were labelled with 6.7 (range 1.9-16.6) Mbq indium-111 oxine and reinfused to the patients. Gamma camera imaging was performed with a GE 400 AT. An accumulation of radioactivity was seen at 54 of 61 sites with enlarged lymph nodes. Increased radioactivity was also seen at 16 sites with no previous clinical evidence of tumour involvement. These data seem very promising and with further methodological improvement lymphoscintigraphy may prove to be an important complement in the staging procedure and follow-up of patients with HD.

Topics: Adolescent; Adult; Aged; Female; Hodgkin Disease; Humans; Hydroxyquinolines; Indium Radioisotopes; Lymph Nodes; Lymphocytes; Male; Middle Aged; Neoplasm Staging; Oxyquinoline; Radionuclide Imaging

The in vitro use of the radioisotope indium 111 (111In) was examined as a radiolabel for lymphocytes obtained from both normal individuals and patients with a variety of lymphoid malignancies. Successful cell labeling requires a chelator. The traditional agent oxine, has proved to be toxic to the lymphoid lineage. Cellular uptake of 111In mediated by the chelator oxine was compared with that of a new chelator, tropolone. Oxine provided better labeling efficiency (48%) than tropolone (35%) for the labeling of normal lymphocytes. By contrast, lymphocytes from patients with chronic lymphocytic leukemia had a nearly twofold greater labeling efficiency when tropolone was substituted for oxine. Further studies demonstrated that tropolone induced functional injury to lymphocytes when mitogenic response to concanavalin A, pokeweed mitogen, and phytohemagglutinin was assessed. Similar toxicity was found when tropolone was compared with oxine. In addition, tropolone produced damaging structural changes seen by both scanning and transmission electron microscopic examination. These changes were both variable and not predictable. Shortening of the incubation time of the chelator with the cell provided the least amount of cellular injury. These findings suggest that tropolone be used as an alternative mediator of lymphocyte labeling with 111In only under critically defined conditions.

Topics: Cells, Cultured; Cycloheptanes; Hodgkin Disease; Humans; Hydroxyquinolines; Indium; Leukemia; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Lymphoma; Microscopy, Electron; Microscopy, Electron, Scanning; Organometallic Compounds; Oxyquinoline; Tropolone