Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in early stages.
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.
Hus
Iwona
I
Haematooncology and Bone Marrow Transplantation Department, Medical University of Lublin, 20-081 Lublin, Poland. iwohus@wp.pl
Kawiak
Jerzy
J
Tabarkiewicz
Jacek
J
Radej
Sebastian
S
Hoser
Grazyna
G
Bojarska-Junak
Agnieszka
A
Schmitt
Michael
M
Giannopoulos
Krzysztof
K
Dmoszynska
Anna
A
Rolinski
Jacek
J
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D001500:BCG Vaccine / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000528:radiation effects*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
D015703:Antigens, CD; D001500:BCG Vaccine; D019496:Cancer Vaccines; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human