Clinical study of dendritic cells and cytokine-induced killer cells for eliminating minimal residual leukemia
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Abstract:
Objective: To evaluate the clinical efficacy and safety of allogenic dendritic cells (DCs) and cytokine-induced killer (CIK) cells combined with chemotherapy for eliminating minimal residual leukemia (MRL). Methods: Forty-eight acute leukemia patients with morphological complete remission (CR) but molecular complete remission (CRm), or patients with minimal residual leukemia (MRL) were selected from Ping’an Hospital of Shijiazhuang during Jan. 2009 to Jun. 2011. According to the patients’ will, 48 patients were divided into combined group and chemotherapy group, with 24 each. All the patients were in the comparable general data and disease level. The combined group was treated with DC-CIK and consolidation chemotherapy, and the chemotherapy group was treated with consolidation chemotherapy. PBMCs were collected from healthy donors (the patient’s parents or children) to prepare DC-CIK cells. DC-CIK cells were intravenous injected into patients once every 15 days, a total of 4-6 times infusion. Expression of leukemia specific and related genes were detected by Real-time PCR. Changes of peripheral lymphocyte subsets and MRL immunophentotype in patients were detected by flow cytometry. Adverse reactions were examined. Results: All the patients were followed up to Jun. 2012. Compared with the chemotherapy group, the CRm rate of combined group was significantly raised (45.8%\[11/24\] vs 8.3% \[2/24\]; χ2=855, P<0.01); the four-color combination flow cytometric immunophenotype of minimal residual leukemia (CFIM) negative conversion rate of patients in the combined group was significantly raised (66.7% vs 25.0%, χ2=8.39, P<001); the negative conversion rate of MRL was significant higher in the combined group (66.7% vs 25.0%, χ2=8.39, P<0.01); the complete remission rate (CCR) of patients in the combined group after 3 years was significantly raised (79.2% vs 45.8%; χ2=569, P<0.05). After treatment the ratio of CD4+/CD8+ lymphocyte was significant increased in the combined group (1.3±0.4 vs 0.8±0.4, P<0.05). No serious adverse reactions were observed after DC-CIK infusion. Conclusion: DC-CIK combined with chemotherapy can inhibit leukemia related gene, promote the negative conversion of CFIM, facilitate the clear of MRL, improve immune function and prolong remission of the patients. No serious adverse reactions are found in patients receiving DC-CIK infusion.
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Project supported by the Major Science and Technology Special Program of Science and Technology Supporting Foundation of Hebei Province (No.09276102D-18)