Antibody responses to leukemia-associated antigens during immunotherapy of chronic myelocytic leukemia

We have studied immunologic reactivity to leukemia-associated antigens in patients with chronic myelocytic leukemia (CML) treated with chemotherapy and adjunctive immunotherapy. All patients were immunologically competent as measured by skin test reactivity to dinitrochlorobenzene. Immunotherapy consisted of allogeneic irradiated leukemic myeloblasts injected intradermally, with BCG vaccine (Research Foundation, Chicago, Ill.) given by multiple puncture at the same site. 10(9) cells plus BCG were given weekly for 4 wk, and 10(8) cells plus BCG were given at monthly intervals thereafter. Eight patients judged clinically to be in the stable phase of their disease developed circulating antibody against the immunizing blast cells demonstrable by cytotoxicity and immunofluorescence assays. The antibody also showed reactivity against a panel of myeloblasts (12 paients) but not against the corresponding remission lymphocytes (five patients) or normal lymphocytes (20 donors). In two cases the antibody showed reactivity against the patient's own leukemic blasts. Seven of these eight patients have maintained a steady clinical course ranging from 20 to 40 mo, while one entered the blastic phase and died. Six patients were judged to be in the aggressive phase of CML because of progressive leukocytosis and splenomegaly or increasing myeloblastosis; five died an average of 16 mo after diagnosis. Humoral antibodies were not detected in these patients after repeated courses of BCG and allogeneic leukemic cells. We conclude that specific active immunotherapy of patients with CML can abet the production of humoral antibody against blast cell antigens and that this response may be impaired during the aggressive phase of the disease.