Effects of Dendritic Cell-activated and Cytokine-induced Killer Cell Therapy on 22 Children with Acute Myeloid Leukemia after Chemotherapy

AML cancer cells

AML cancer cells

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Summary

This study investigated the efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. The results conclude, MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects.

Patients characteristics

22 patients with histologically confirmed acute myeloid leukemia (AML). Among the 22 children, there were 11 boys and 11 girls with their age ranging from 3 to 14 years old. All of them received regular chemotherapy of AML-XH-99 protocol and reached CR.

Methodology

DC-CIK generation
Mononuclear cells were isolated from 50 mL of bone marrow under sterile condition and induced into DCs in vitro in the serum-free culture medium (AIMV) containing granulocyte-macrophage colony-stimulating factor (GM-CSF) 1000 U/mL, inter- leukin -4 (IL-4) 1000 U/mL, stem cell factor (SCF) 10 ng/mL, TNF-a 1000 U/mL, IL-6 10 ng/mL, IL-3 10 ng/mL.
Ten days later, the peripheral blood mononuclear cells (PBMCs) were collected with Cobe Spectra Apheresis System (COBE Spectra) and adjusted to a density of 1×106/mL. DCs and PBMCs were co- cultured in the culture medium (AIMV) supplemented with IFN-y 2000 U/mL, IL-2 1000 U/mL, anti-CD3 monoclonal antibody 50 μg/L. The culture medium was changed every two to three days, and the cells were cultured in Cellstar cell culture flasks (650 mL) with 5% CO2 at 37°C. The expansion period was maintained for 10–15 days till the cell number was around 5×109 for every patient.

Treatment

After centrifugation, DC-CIK cells were washed once with 0.9% sodium chloride including 2% albumin and then suspended in 300–400 mL 0.9% sodium chloride with 5% albumin and IL-2 1000 U/mL in the 500 mL medical infusion bags.
DC-CIK cells were divided into two parts and infused to the patients themselves at an interval of 24 hours. Usually, the final DC-CIK products were infused into the patients in 30 min. After the second infusion of DC-CIK cells, all patients were injected with IL-2 1×106 U/day subcutaneously every other day for a total of 10 times.

Results

Before infusion, the tumor killing activity of DC-CIKs was confirmed. The results of lymphocytes subsets in 15 cases of AML before and 3 months after DC-CIKs therapy, it was found that the ratio of CD3+/CD8+ cells was increased dramatically after the therapy, suggesting the significant increase of cytotoxic CIKs in the patients.
Outcomes
One patient received three DC-CIK therapies (interval=3 months), 2 patients received two (interval=3 months), and the remaining patients received one therapy. All patients reached CR before the DC-CIK therapy. The median follow-up duration from DC-CIK infusion was 71 months, ranging from 30 to 108 months. Twenty patients were in consistent CR (90.9%); two cases (9.1%) relapsed (one relapsed 19 months after DC-CIK therapy and the other relapsed 28 months after the treatment). Five cases were MRD positive before treatment but became negative during re-check, 3 months after the therapy. After the treatment, the genes of AML1/ETO-positive samples became negative.
Side effects
There were no side effects in patients before treatments. For the infusion of DC-CIK, 7 patients showed side effects (31.28%). Among them, 6 (27.27%) patients suffered from high fever and chills which were easily treated with fever drugs and Phenergan. Hives were found on 3 (13.64%) patients and 2 (9.09%) patients had low fever after infusion and the symptom disappeared without special medical care. No obvious side effects were observed during the period of IL-2 treatment. No damages were found in heart, liver and kidney. Blood routine test showed blood cells were in normal range before and after treatment.

Conclusion

DC-CIK therapy is relatively safe with few side effects. The therapy can eliminate the leukemia cells and eradicate MRD in children with AML in a short time of follow-up.

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Scientific article publishing date: 10/22/2015

Immucura identifier BSC21_327EN

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