Clinical and laboratory studies on human lymphona
The thesis is in two parts. The first concerns a laboratory study of human lymphoma cells and their interactions with reticulo-endothelial cells. Electron microscopy and tissue culture studies indicated that macrophages and lymphocytes were in close contact with tumour cells but no cytocidal effect was noted in the intact tissue. A time lapse film of lymph nodes in culture shows that when ceils are teased, out in a monolayer, the tumour cells become susceptible to direct attack by lymphocytes and tissue macrophages. Lymph node cultures of lymphoma liberate chemotactic factors to the supernatant which attract eosinophils, monocytes and leucocytes. The eosinophil chemotactic factor was found in high concentrations only in lymph nodes involved with Hodgkin's disease. Also in the supernatants were found two factors which depressed host cells. After incubation of suoernatants with lymphocytes, their subsequent ability to transform was depressed and after incubation with normal monocytes, subsequent chemotaxis was inhibited. Peripheral blood monocytes from lymphoma patients were significantly less mobile than age-sex match controls in a chemotaxis assay. The clinical part of the thesis describes firstly a search, for space-time clusters in the occurrence of lymphomas in the South East of Scotland over a period of eleven years. Fourteen clusters were found from centralised computer records but only one of these survived closer scrutiny. Secondly a cohort of one hundred consecutive patients with lymphoma has been followed for two to seven years. Overall survival of 68°/o is considerably superior to retrospective studies which took place before 1970. Improvement in survival is due to rigorous staging, more appropriate radiotherapy and the advent of effective chemotherapy. Several serum parameters such as low albumin, low immunoglobulin M and low serum a macroglobulin independently worsened the prognosis. This information taken with the findings of the laboratory studies suggest that immunodeficiency in lymphoma patients is accompanied by a poor prognosis and maybe due to release of tumour specific factors. Such high risk patients should be managed by intensive immunological support including removal of such factors and restoration to high protein levels prior to or along with cytoreductive therapy.