Treating Acute Myeloid Leukemia with Sequential Autologous Leukemia Antigen-Loaded DC-CIK Cells after Chemotherapy: A Retrospective Study

Special Article - Acute and Chronic Myeloid Leukemia

Ann Hematol Oncol. 2016; 3(12): 1126.

Treating Acute Myeloid Leukemia with Sequential Autologous Leukemia Antigen-Loaded DC-CIK Cells after Chemotherapy: A Retrospective Study

Si-han Lai, Deng R, Fu L, Yi H, Fang-yi Fan, Wang Y, Qiu L, Yi-lan Liu, Ye-cheng Li, Xiao-juan Miao, Yan-rong Shuai, Guang-cui He and Su Y*

Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Cheng Du, Sichuan 610083, P. R, China

*Corresponding author: Yi Su, Department of Hematology and Hematopoietic Stem Cell Transplantation and Cell Immunotherapy Center, Cheng Du Military General Hospital of PLA, Rong Du Avenue 270#, Cheng Du, Sichuan, 610083, P. R, China

Received: November 11, 2016; Accepted: December 27, 2016; Published: December 30, 2016


To retrospectively analyze the clinical safety and effectiveness of treating acute myeloid leukemia (AML) with sequential autologous leukemia antigenloaded DC-CIK cells after chemotherapy. Four hundred AML patients were divided into treatment (n=210) and control (n=190) groups, and categorized into favorable, intermediate, and poor risk sub-groups according to NCCN guidelines. DC-CIK cellular parameters were measured by flow cytometry. Treatmentrelated adverse responses were observed, and the clinical efficacies were compared between groups and among the favorable, intermediate, and poor risk sub-groups. Patients in the treatment group underwent at least four DCCIK infusions. The CD3+:CD8+ and CD3+:CD56+ ratio of the DC-CIK cells was 78.3±4.3% and 35.1±3.5%, respectively, which was significantly higher than in CIK cells 52.1±3.8% and 19±3.1% (both P<0.05). Patient overall survival (OS) (54.8% vs. 37.9%, P<0.05) and disease-free survival (DFS) (49.5% vs. 32.1%, P<0.05) in the treatment group was significantly higher than the control group. OS of treatment group patients in the favorable, intermediate, and poor sub-groups was 73.4%, 52.9%, and 10.3%, and was 51.5%, 36.1%, and 8.0% in the control group, respectively. Treatment group patient OS in the favorable and intermediate risk sub-groups was significantly higher the control group (P<0.05). however, the outcomes of the poor risk AML patients could not be improved (P>0.05). Thirty-one (14.7%) treatment group patients had only transient minimal adverse responses. Sequential infusion of DC-CIK cells could significantly increase DFS and long-term survival of favorable and intermediate risk AML patients. For poor risk AML patients, we suggest immediate HSCT therapy after induction of remission.

Keywords: AML; DC-CIK; Immunotherapy


Traditional therapy of treating acute myeloid leukemia (AML) includes predominantly chemotherapy and hematopoietic stem cell transplantation (HSCT). The relatively high relapse rate and incidence of multidrug resistance (MDR) are major challenges in treating AML. In recent years, using targeted therapy, demethylation therapy, and immunotherapy to treat AML has been acknowledged as an intense area of recent research.

Immunotherapy based on dendritic cell (DC)-activated Cytokine-induced killer (CIK) has been increasingly used in clinical practice. Cytokine-induced killer cells (CIKs) are a group of heterogeneous cells obtained by the in vitro culture of peripheral blood mononuclear cells (PBMCs) under the co-stimulation of IFN-γ, anti-CD3 mAb, and IL-2. CIKs have the advantages of both the powerful anti-tumor activities of T cells and the restricted tumor killing effects of the major histocompatibility complex (MHC) of NK cells, complemented by a powerful proliferation capacity and high cytotoxicity [1].

Dendritic cells (DCs) are the most potent professional antigen-presenting cells that play important roles in inducing the primary immune response. Co-culture of CIKs that display a potent cell-mediated killing capacity and DCs that exhibit powerful antigen presenting capacity could significantly increase the proliferation and killing capacity of CIKs [2].

Multiple studies have shown that treating various tumors by adoptive immunotherapy based on a strategy of using DCCIKs display very acceptable prospects in clinical practice, and especially in the elimination of minimal residual disease (MRD) of leukemia [3-6]. In the present study, autologous leukemia antigenloaded DC-CIKs were used for the treatment of AML patients. Additionally, the safety profiles and clinical efficacies were investigated, and the results reported herein.

Patients and Methods


Four hundred AML patients (PML/PARα positive AML patients were excluded) that were diagnosed at our hospital between January 2009 and July 2015 were randomly included. AML was diagnosed according to the AML French-American-British (FAB) and the WHO classification criteria [7-8].

The present study was approved by the Ethics Committee of the General Hospital of Chengdu Military Region. The inclusion criteria were as follows: 1) patients were confirmed as favorable, moderate, or high risk AML. The risk status of the patients were classified according to the NCCN AML guidelines (2016); 2) the induction chemotherapy for patients <60 years of age used the DA or IDA regimen (D: daunorubicin; A: cytarabine; ID: idarubicin), while for patients =60 years of age, the induction chemotherapy regimen using CAG was employed (C: Aclarubicin; A: cytarabine; G: granulocyte colonystimulating factor). The consolidation and maintenance therapy of patients used cytarabine-based regimens; and 3) patients in the treatment group signed informed consent documentation prior to adoptive transfer of DC-CIKs.

The exclusion criteria were as follows: 1) combined with severe chronic consumptive diseases, or combined with severe liver, heart, or renal disease; 2) could not complete four or more cycles of chemotherapy due to any reason; and 3) the families of the patients required receipt of other treatment methods.

The patients were divided into two groups according to treatment or no treatment by adoptive transfer of DC-CIK. For patients in the treatment group, sequential DC-CIK infusion was performed after chemotherapy, while for patients in the control group, only chemotherapy was performed. The age, sex, disease type, and risk status were not significantly different between either group (Table 1).