Immunotherapy of chronic myelocytic leukemia: effects of different vaccination schedules.

In a clinical trial of immunotherapy in chronic myelocytic leukemia, 62 patients received repeated intradermal injections of BCG-cultured cell mixtures, while 16 were vaccinated with BCG alone. The lymphoblastoid cell lines used for vaccination were established from blood of patients with advanced myeloid leukemia and were reactive with "specific" primate antisera against myeloid leukemic cells. Both sensitization to target cell antigens and substantial general increases in delayed hypersensitivity responses were recorded among immunized patients. Major immunologic complications (hypersensitivity and "autoimmune" phenomena) were observed in 10 patients. These complications were attributable to the BCG content of vaccines, and their incidence correlated with intensity of immunologic stimulation. Data from cases in which intermittent busulfan therapy was used provided suggestive evidence that immunotherapy (either with BCG-cell mixtures or with BCG alone) prolonged unmaintained remissions in one-third of the patients. Among 48 "good-risk" patients, there was an inverse correlation between intensity of immunologic stimulation and survival. The survival of 18 patients who received the most intensive vaccination schedule was identical to that of controls. Survival of the other 30 patients was significantly better (p = 0.03), with an increase of 2 years in median survival. Survival of 30 poor-risk patients (24, most intensive vaccination schedule) was identical to that of controls. We conclude that immunologic stimulation may produce worthwhile prolongation of life in CML but that overly aggressive schedules of immunotherapy abrogate this effect. Our experience raises the question whether results in other clinical trials of immunotherapy may have been adversely affected by excessive frequency or dosage of immunologic stimulants.