Abstract
To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 109–1 × 1010) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of β2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.
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Ferlay, J., Bray, F., Pisani, P., & Parkin, D. M. (2004). GLOBOCAN 2002: Cancer incidence, mortality and prevalence worldwide. IARC cancer base no. 5 version 2.0. Lyon: IARC-Press.
Horner, M. J., Ries, L. A. G., Krapcho, M., Neyman, N., Aminou, R., Howlader, N., et al. (Eds.). (2009). SEER cancer statistics review, 1975–2006. Bethesda, MD: National Cancer Institute, http://seer.cancer.gov/csr/1975_2006/, based on November 2008 SEER data submission, posted to the SEER web site.
Bernardi, D., Milan, I., Balzarotti, M., Spina, M., Santoro, A., & Tirelli, U. (2003). Comprehensive geriatric evaluation in elderly patients with lymphoma: Feasibility of a patient-tailored treatment plan. Journal of Clinical Oncology, 21, 754.
Coiffier, B., Lepage, E., Briere, J., Herbrecht, R., Tilly, H., Bouabdallah, R., et al. (2002). Gisselbrecht, CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large B-cell lymphoma. New England Journal of Medicine, 346, 235–242.
Zagonel, V., Monfardini, S., Tirelli, U., Carbone, A., & Pinto, A. (2001). Management of hematologic malignancies in the elderly: 15-Year experience at the Aviano Cancer Center, Italy. Critical Reviews in Oncology/hematology, 39, 289–305.
Weng, D. S., Zhou, J., Zhou, Q. M., Zhao, M., Wang, Q. J., Huang, L. X., et al. (2008). Minimally invasive treatment combined with cytokine-induced killer cells therapy lower the short-term recurrence rates of hepatocellular carcinomas. Journal of Immunotherapy, 31, 63–71.
Balducci, L., & Yates, J. (2000). General guidelines for the management of older patients with cancer. Oncology, 14, 221–227.
Yancik, R., & Ries, L. A. (2004). Cancer in older persons: An international issue in an aging world. Seminars in Oncology, 31, 128–136.
Talarico, L., Chen, G., & Pazdur, R. (2004). Enrollment of elderly patients in clinical trials for cancer drug registration: A 7-year experience by the US Food and Drug Administration. Journal of Clinical Oncology, 22, 4626–4631.
Leemhuis, T., Wells, S., Scheffold, C., Edinger, M., & Negrin, R. S. (2005). A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biology of Blood and Marrow Transplantation, 11, 181–187.
Takayama, T., Sekine, T., Makuuchi, M., Yamasaki, S., Kosuge, T., Yamamoto, J., et al. (2000). Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: A randomised trial. Lancet, 356, 802–807.
Schmidt-Wolf, I. G., Finke, S., Trojaneck, B., Denkena, A., Lefterova, P., Schwella, N., et al. (1999). Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma. British Journal of Cancer, 81, 1009–1016.
Introna, M., Borleri, G., Conti, E., Franceschetti, M., Barbui, A. M., Broady, R., et al. (2007). Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: A phase I study. Haematologica, 92, 952–959.
Nagler, A., Berger, R., Ackerstein, A., Czyz, J. A., Diez-Martin, J. L., Naparstek, E., et al. (2010). A randomized controlled multicenter study comparing recombinant interleukin 2 (rIL-2) in conjunction with recombinant interferon alpha (IFN-alpha) versus no immunotherapy for patients with malignant lymphoma postautologous stem cell transplantation. Journal of Immunotherapy, 33, 326–333.
Eklund, J. W., & Kuzel, T. M. (2004). A review of recent findings involving interleukin-2-based cancer therapy. Current Opinion in Oncology, 16, 542–546.
Antony, G. K., & Dudek, A. Z. (2010). Interleukin 2 in cancer therapy. Current Medicinal Chemistry, 17, 3297–3302.
Poire, X., Kline, J., Grinblatt, D., Zimmerman, T., Conner, K., Muhs, C., et al. (2010). Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapse or refractory lymphomas. Leukemia and Lymphoma, 51, 1241–1250.
Jiang, J., Xu, N., Wu, C., Deng, H., Lu, M., Li, M., et al. (2006). Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Research, 26, 2237–2242.
Wu, C., Jiang, J., Shi, L., & Xu, N. (2008). Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer. Anticancer Research, 28, 3997–4002.
Shi, M., Zhang, B., Tang, Z. R., Lei, Z. Y., Wang, H. F., Feng, Y. Y., et al. (2004). Autologous cytokine-induced killer cell therapy in clinical trial phase I is safe in patients with primary hepatocellular carcinoma. World Journal of Gastroenterology, 10, 1146–1151.
Lu, P. H., & Negrin, R. S. (1994). A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. Journal of Immunology, 153, 1687–1696.
Harris, N. L., Jaffe, E. S., Diebold, J., Flandrin, G., Muller-Hermelink, H. K., Vardiman, J., et al. (1999). World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. Journal of Clinical Oncology, 17, 3835–3849.
Jaffe, E. S., Harris, N. L., Stein, H., & Isaacson, P. G. (2008). Classification of lymphoid neoplasms: The microscope as a tool for disease discovery. Blood, 112, 4384–4399.
Lister, T. A., Crowther, D., Sutcliffe, S. B., Glatstein, E., Canellos, G. P., Young, R. C., et al. (1989). Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin’s disease: Cotswolds meeting. Journal of Clinical Oncology, 7, 1630–1636.
Cheson, B. D., Pfistner, B., Juweid, M. E., Gascoyne, R. D., Specht, L., Horning, S. J., et al. (2007). Revised response criteria for malignant lymphoma. Journal of Clinical Oncology, 25, 579–586.
Cheson, B. D., Horning, S. J., Coiffier, B., Shipp, M. A., Fisher, R. I., Connors, J. M., et al. (1999). Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. Journal of Clinical Oncology, 17, 1244–1253.
Wang Y, Dai H, Li H, Lv H, Wang T, Fu X, et al. (2011) Growth of human colorectal cancer SW1116 cells is inhibited by cytokine-induced killer cells. Clinical and Developmental Immunology, 2011, 621414.
Schag, C. C., Heinrich, R. L., & Ganz, P. A. (1987). Karnofsky performance status revisited: Reliability, validity, and guidelines. Journal of Clinical Oncology, 2, 187–193.
Herberman, R. B. (1987). Cancer therapy by biological response modifiers. Clinical Physiology & Biochemistry, 5, 238–248.
Sangiolo, D., Marinuzzi, E., Todorovic, M., Vitaggio, K., Vallario, A., Jordaney, N., et al. (2008). Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: Implications for their infusion across major HLA barriers. International Immunology, 20, 841–848.
Scheffold, C., Brandt, K., Johnson, V., Lefterova, P., Degen, B., Schöntube, M., et al. (1995). Potential of autologous immunologic effector cells for bone marrow purging in patients with chronic myeloid leukemia. Bone Marrow Transplantation, 15, 33–39.
Linn, Y. C., Lau, L. C., & Hui, K. M. (2002). Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukemic blasts. British Journal Haematology, 116, 78–86.
Acknowledgments
This study was supported by the Chinese National Natural Science Foundation (grants No. 30772597 and No. 30873086), Chinese Central Health Committee Foundation (B2009B115), Innovation and Nursery Foundation of Chinese PLA General Hospital (09KMM42) and supported in part by a grant from the Ministry of Science and Technology of China (2010CB912802 and 2008ZXJ09001-019).
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X. Lu and B. Yang contributed equally as first authors.
X. Lu and W. Han contributed equally as common corresponding authors.
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Lu, Xc., Yang, B., Yu, Rl. et al. Clinical Study of Autologous Cytokine-Induced Killer Cells for the Treatment of Elderly Patients with Diffuse Large B-Cell Lymphoma. Cell Biochem Biophys 62, 257–265 (2012). https://doi.org/10.1007/s12013-011-9273-6
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DOI: https://doi.org/10.1007/s12013-011-9273-6