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.

Specificity of heteroantisera to human acute leukemia-associated antigens.

Antisera have been raised to human leukemic blast cells from individual patients in mice rendered tolerant with cyclophosphamide to remission leukocytes from the same individual. 10 antisera were raised against acute myelogenous leukemia (AML) cells and 5 antisera were raised against acute lymphoblastic leukemia (ALL) cells. Antisera to AML cells were absorbed with ALL cells, and antisera to ALL cells were absorbed with AML cells. Unabsorbed and absorbed antisera as well as antisera raised in nontolerant mice were tested for cytotoxicity against various cells of a panel containing myeloblasts from 35 patients with AML, lymphoblasts from 7 patients with ALL, myeloblasts from 7 patients with chronic myelogenous leukemia (CML) in blast crisis, peripheral blood leukocytes from 12 patients with acute leukemia in remission and 30 nonleukemic patients, and nucleated bone marrow cells from 10 nonleukemic patients. Unabsorbed antisera to AML or ALL cells raised in tolerant mice were highly cytotoxic to leukemic blasts cells but significantly less cytotoxic to remission and control cells. Antisera to AML cells absorbed with ALL cells retained measurable cytotoxicity against AML cells but were not cytotoxic to ALL cells or control cells. Similarly, antisera to ALL cells absorbed with AML cells retained significant cytotoxicity only to ALL cells. Control antisera raised in nontolerant mice were cytotoxic to all cells tested. Although species specific, histocompatibility, differentiation, maturation, and cell cycle-associated antigens may be responsible in part for the cytotoxic activity of the unabsorbed antisera, the absorbed antisera are probably detecting antigens specific for their leukemic cell type.