Autologous Dendritic Cells Combined with Cytokine-induced Killer Cells Synergize Low-dose Chemotherapy in Elderly Patients with Acute Myeloid Leukaemia

Acute Myeloid Leukaemia

Acute Myeloid Leukaemia

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Summary

The goal of the study is to see if it’s possible to culture dendritic cells (DCs) and cytokine-induced killer (CIK) cells obtained at the time of an initial diagnosis of AML in elderly patients, as well as the safety and efficacy of using autologous DCs and CIK cells in combination with low-dose chemo therapy in these patients. Immunotherapy using autologous DCs and CIK cells has been proven to be a potential candidate for treating AML in the elderly.

Patients characteristics

A total of 44 elderly patients with AML aged >60 years old were included in the study. Patients must have no acute promyelocytic leukemia, according to the World Health Organization’s classification, no combined secondary tumour or autoimmune disease and no hepatitis virus or immunodeficiency virus infection.
All patients are divided into two groups, n=21 in the immunotherapy group (DCs and CIK cells in combination with low-dose chemotherapy) and 23 in the control group (low-dose chemotherapy only).

Methodology

DC-CIK cell preparations
For patients in the immunotherapy group, blood was taken at the time of AML diagnosis for the generation of DCs and CIK cells. Blood collection was carried out after making sure that there were no abnormalities in body temperature, blood coagulation, liver and kidney function, and after examination of electrocardiogram and chest computed tomography images.
A blood cell separator was used to separate 2.0 × 109 PBMCs containing leukaemic blasts; 10 ml of autologous plasma was also collected. The PBMCs were split into two batches to enrich for DCs and CIK cells separately.
The first batch of PBMCs containing leukaemic blasts was used to enrich DCs by adding to a six-well plate with X-VIVOTM 20 serum-free medium with 80 mg/ml gentamycin at a cell density of 2.5 × 106 cells/ml. Then, 1000 IU/ml GM-CSF, 100 IU/ml interferon (IFN)-α, 100 ng/ml FLT-3 ligand, 50 IU/ml stem cell factor, and 0.25 ng/ml transforming growth factor (TGF)-β were added and cells were cultured at 37 °C in 5% carbon dioxide.

Treatment

Chemotherapy
Patients in the immunotherapy group were started on low-dose chemotherapy (14-day course) immediately after collecting the PMBCs, i.e., at the same time that autologous DC and CIK cell culture was started. After blood collection, patients in both the immunotherapy and control groups received a single course of the following chemotherapy regimen (low-dose HAG): 200 μg/m2 GM-CSF by subcutaneous (S.C.) injection once daily for 14 days; 10 mg/m2 cytosine arabinoside by SC. injection every 12 hours for 14 days; and 1 mg/day homoharringtonine by intravenous (I.V.) injection every day for 14 days.
DC-CIK administration
On day 7 after completion of chemotherapy (day 21), combined transfusion of DCs and CIK cells was carried out in the immunotherapy group in the absence of any obvious bacterial, fungal, endotoxin, ormycoplasma infection. The DCs were thawed and added to CIK cells which had been in culture for 21 days. Patients in the immunotherapy group received a total mean ± SD of 7.36 ± 0.48×107 DCs and 5.47 ± 1.3 × 109 CIK cells by I.V. transfusion, at a rate of 0.3 ml/min over 30 min once daily on each of 5 days. Each day, one-fifth of the total cells were suspended in 100 ml normal saline and 6 – 10 ml of autologous plasma from the patients was added; a fresh suspension was made on each of the 5 days.

Results

Clinical outcomes
The total effect rate in the immunotherapy group (CR + PR) was significantly higher than that in the control group. In the immunotherapy group, one patient classified with a poor prognosis reached partial response (PR), the other three patients classified with a poor prognosis had disease progression (PD).
In the control group, all six patients classified with a poor prognosis had disease progression (PD); two died within 2 weeks of completion of chemotherapy. Following treatment, in the immunotherapy group the mean ± SD Karnofsky score was significantly higher (71.90 ± 12.09) than in the control group (60.00 ± 23.39).
Adverse events
Adverse events resulting from the transfusion of DCs and CIK cells included eight cases of feeling cold, five cases of myalgia and seven cases of noninfective fever. Generally, noninfective fever lasted 4 – 7 hours and body temperature were 37.5 – 38.5 °C. These adverse events were observed only in the immunotherapy group and occurred in the initial 48 hours after receiving treatment. They were regarded as being related to the immunotherapy treatment. No adverse events were observed in the control group. All adverse events in the immunotherapy group were relieved with symptomatic treatment. There was no change before and after transfusion in electrocardiogram, liver and kidney functions.

Conclusion

In conclusion, this study showed that immunotherapy with autologous DCs and CIK cells significantly increased immunity, as measured by levels of cytokines and T-cells before versus after treatment in elderly patients with AML when given with conventional chemotherapy.

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Scientific article publishing date 6/16/2012

Immucura identifier BSC21_285EN

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