Successful alternative treatment for relapsed adult Acute Lymphoblastic Leukemia with Dendritic Cells- Cytokine-Induced Killer Cells combined with a rituximab-based regimen

Change in Expressions

Change In Expression

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Summary

This study investigates the efficacy and safety of DC-CIK for patients with Acute lymphoblastic leukemia (ALL) that are unable to tolerate chemotherapy. The results suggests , relapsed ALL was successfully treated with DC-CIK combined with a rituximab regimen.

Patients characteristics

A 52-year-old man first presented with persistent fever and weakness in May 2014. Blood analysis showed reduced white blood cell and platelet counts. A bone marrow aspirate revealed 72% immature blast cells, and immunophenotypic analysis showed that the blast cells expressed CD10, CD19, CD22, CD79a, and human leukocyte antigen-D related cells.

Methodology

Culture of DC
Mononuclear cells (MNC) were isolated with lymphocyte separating medium and washed by serum-free RPMI 1640 culture medium. They were cultured in RPMI 1640 medium for 2 hours. Adherent cells were suspended in RPMI 1640 culture medium which contained rhGM-CSF 550 U/mL, rhIL 4 500 U/mL, rhSCF 100 μg/L, rhTNF-α 10 μg/L for 10 days. Medium was changed every other day for half dose and added with cytokines.
Culture of CIK
Non-adherent cells of cord blood MNC were collected, washed with serum-free RPMI 1640 culture medium and the MNC cell concentration was adjusted to 1×106/m. Interferon- α (IFN- α) 1 000 U/mL was addedand they were cultured in the CO2 incubator at constant temperature 37°C. After 24 hours, 1 g/mL CD3 monoclonal antibody, 1 000 U/mL recombinant human interleukin-2 (rh IL-2) and 300 U/mL recombinant human interleukin-1 (rh IL-1) were added. Medium was changed every three days for half dose and added with cytokines to maintain the cell concentration at (1-2)×106/mL.

Treatment

The patient received the standard VDCLP regimen consisting of vincristine, daunorubicin, cyclophosphamide, l-asparaginase, and prednisone. At first, he achieved complete remission with 3.5% blast cells in the bone marrow. However, severe side effects caused by induction therapy, including febrile neutropenia, hyperglycemia, and hepatic toxicity eventually followed.
After the administration of high-dose methotrexate combined with l-asparaginase and MA (mitoxantrone combined with intermediate-dose cytarabine) consolidation therapies, neutropenia persisted for 2 months, during which he was affected by pulmonary
infection, sepsis, and liver dysfunction. The patient refused to receive any maintenance therapy because of significant complications.
Six months later, the patient presented with fatigue and petechiae with a short CR1. His bone marrow with ++++
31% blast cells was consistent with relapsed B cell ALL (CD19 , CD34 , CD45 , and CD10 ). Therapeutic approaches for this patient in such a poor performance status were limited. The option of DC-CIK was then adopted.

Results

At the first infusion, the proportion of CD3+CD56+ cells among the DC-CIK cells was 42%. The cultured DC-CIK cells inhibited the K562 cells by 58.3%. The ratio of CD8+ and CD56 cells in the peripheral blood of the patient after the first infusion was 42.23% and 53.04%, respectively.
During the infusion, no malfunctions in electrocardiography and no liver–renal abnormalities were observed. Subsequently, the rituximab combined with the vincristine, daunorubicin, l-asparaginase, and prednisone regimen was adopted, and a second remission was achieved without significant side effects.
Thereafter, four rounds of consolidation therapy including rituximab were administered, during which seven cycles of DC-CIK cells were infused alternately (each infusion comprised (4–6) ×109 cells in a volume of 300 mL). Before administration, cocultured DC-CIK cells were collected. The patient had no complaints during the infusion.
Thereafter, the patient received rituximab alone every 3 months for a year and took thioguanine and methotrexate tablets at specific intervals of immunotherapy until March 11, 2017. Impressively, the patient has been in bone marrow remission since his last relapse.

Conclusion

The use of DC-CIK is evidently safe and effective in relapsed acute lymphoblastic leukemia (ALL) and could improve clinical symptoms in leukemia patients.

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Scientific article publishing date 8/4/2018

Immucura identifier BSC21_261EN

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