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Clinical and in vitro observations in cancer patients during immunotherapy Clements, Donna V. M.


The value of immunotherapy, in conjunction with radiotherapy, chemotherapy and surgery, in controlling cancer is slowly becoming established. Reported here are clinical and in vitro observations on the effect of BCG immunization in a preliminary study of patients with lymphomas and of BCG, PPD, and vaccinia virus in the management of malignant melanoma. As oral BCG was used in these patients to stimulate the maximum amount of lymphoid tissue, it was deemed necessary to determine whether oral BCG was an effective means of inducing sensitivity. Consequently, normal healthy volunteer student nurses were divided into two groups; one group received oral BCG while the second group were immunized with intradermal BCG. Follow-up skin testing showed a much lower degree of sensitivity in those nurses who had received oral BCG. This difference, however, was not apparent using an in vitro assay to determine sensitivity. Maintenance of remission solely by repeated BCG vaccinations in seven patients with non-Hodgkin's lymphoma who had achieved a complete clinical remission with initial standard therapy has provided sufficient encouragement to begin a randomized clinical trial. In vitro lymphocyte responses to mitogens and PPD used as parameters of cell-mediated immunity have not proved to be of value in predicting early or late recurrence in pre-trial and trial patients. Eight out of twenty-one patients with malignant melanoma have shown a satisfactory clinical response to immunotherapy. Those who respond must show immunological reactivity to the stimulating agent, however the best clinical responses were not associated with the highest degrees of in vivo and in vitro sensitization. The skin reactivity and the in vitro lymphocyte response to PPD as well as a 2 - 3 fold increase in the appearance of colony-forming units in the peripheral blood following the intratumour injection of BCG or PPD are helpful in prognosis and management of these patients. In general patients with malignant melanoma who presented with a PHA response less than 40% of normal made a poor response to immunotherapy. Autopsies performed on seven patients dying with extensive melanocarcinomatous disease failed to show any serious adverse toxic reactions or infections from oral and intratumour injections of BCG.

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