Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in early stages

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In this study 10(7) peripheral blood mononuclear cells including on average 78.56% CD19+/CD5+ lymphocytes were irradiated, and then administered intradermally as an anti-cancer vaccine to seventeen patients with B-cell chronic lymphocytic leukemia (B-CLL) at early stages (twelve injections, four at a weekly interval followed by eight vaccines given every two weeks). In eight out of seventeen patients, in the first two injections, irradiated leukemic cells were mixed with bacillus Calmette-Guerin (BCG) to improve the efficacy of therapy by additional induction of innate immunity. A hematological improvement (as defined by a >25% reduction of leukocyte count) to autologous leukemic cell vaccines was observed in 5/17 patients, stabilisation of disease in 5/17 patients and in 7/17 patients there was no response to immunotherapy. In seven patients significant increase of the lymphocyte doubling time was noted (p=0.02). There was no impact of BCG for immune responses or clinical outcome of vaccinated patients, but there was a significant increase of the absolute counts of CD3+ as well as of CD3+/CD4+ and CD3+/CD8+ T cells during the vaccination period. We observed a significant improvement of the phagocytic function of autologous dendritic cells generated from peripheral blood monocytes obtained from patients with B-CLL after the end of immunotherapy (p=0.006). An association between the clinical outcome and the percentage of leukemic cells positive for expression of ZAP-70 and CD38 was noted. In conclusion, our results demonstrated the feasibility and safety of autologous irradiated leukemic cell immunotherapy in patients with B-CLL. As we noted immunological, and to some extent, clinical responses, this approach merits further investigation, including the use of adjuvants other than BCG.