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

Dong, Min; Liang, Der Cherng; Li, Y; Kong, Desheng; Kang, Pan; Li, K; Ping, Chow Yock; Zhang, Y; Zhou, Xinna; Hong, Luojia

doi:10.1177/147323001204000405

Cited by 13 publications

(17 citation statements)

References 26 publications

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“…[31] Interestingly, autologous dendritic cells plus cytokine-induced killer cells were also shown to synergize with low-dose chemotherapy [response rate (RR) of 71.4 vs. 39.1% for controls]. [32] In our elderly patient with comorbodities and high-risk cytogenetics, we gave oral metronomic induction because of the choice of the patient and based on our previous experience. [8][9][10] The combination of oral metronomic chemotherapeutic agents was not only well tolerated, but our patient also did not require any hospitalization during induction.…”

Section: Discussionmentioning

confidence: 99%

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

et al. 2013

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Acute myeloid leukemia (AML) in older adults differs biologically and clinically from that in younger patients and is characterized by adverse chromosomal abnormalities, stronger intrinsic resistance, and lower tolerance to chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite intensive chemotherapy, and most of them die within a year of diagnosis. Over the last decade, metronomic chemotherapy has emerged as a potential strategy to control advanced/refractory cancer. Here, we report a case of a 68-year-old gentleman having AML with high-risk cytogenetic features, who achieved complete remission on our oral metronomic PrET (PrET: Prednisolone, etoposide, thioguanine) protocol on an outpatient basis. He was later treated with standard high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance with etoposide, thioguanine, and sodium valproate. Presently, the patient is nearly 35 months since diagnosis and 21 months off treatment. This case report and review highlights that the combination of oral low-intensity metronomic therapy, followed by standard HD consolidation therapy and metronomic maintenance therapy may be well tolerated by elderly patients especially with less proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit for intensive intravenous induction chemotherapy regimens. References for this review were identified through searches of Pubmed for recent publications on the subject as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

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Section: Discussionmentioning

confidence: 99%

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

et al. 2013

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“…These effects include delayed-type hypersensitivity (DTH) skin test reactions, which essentially confirms the ability of the DCs to elicit T-cell-mediated immunity in vivo [52]. Other (non-specific) signs of the immunogenicity of DC therapy that have been observed include: increases in CD4 + and/or CD8 + T-cell frequencies during or after DC administration [49,53], enhanced activation of CD4 + T cells, as evidenced by their increased IFN-γ production following DC therapy [48], and elevations in plasma levels of immunostimulatory or T H 1-polarizing cytokines (such as interleukin (IL)-2) [48,49,52]. Regarding the increased IFN-γ expression, it should be mentioned that IFN-γ can in turn have an effect on DCs.…”

Section: Clinical Use Of Dcs For Immunotherapy Of Amlmentioning

confidence: 96%

“…It is also a predictive factor of imminent relapse in AML patients, including those that received allo-SCT, even when other markers are not available [70,71,72,73]. Only one study [49] reported CR and partial remissions (PR) in the relapsed/refractory setting. It is important to note, however, that these patients also received chemotherapy and CIKs, making it difficult to draw conclusions about the effectiveness of DCs as a stand-alone treatment for advanced AML.…”

Section: Clinical Use Of Dcs For Immunotherapy Of Amlmentioning

confidence: 99%

“…Abbreviations: n , number of DC-treated patients; †, including two patients with acute lymphoblastic leukemia (ALL); DC type, type of DC used; auto, DCs from autologous origin; allo, DCs from allogeneic origin; moDCs, monocyte-derived DCs; ‖, in combination with systemic administration of the Toll-like receptor agonist OK432; AML-DCs, AML cell-derived DCs; **, in combination with cytokine-induced killer cells and low-dose chemotherapy (for further details, see [49]); Antigen, antigenic material used to load DCs; loading, antigen-loading method used; Apo-AML cells, apoptotic AML cells; NA, not applicable; WT1, Wilms’ tumor 1 antigen; ND, no data; ↑, increase; hTERT, human telomerase reverse transcriptase; PRAME, preferentially expressed antigen in melanoma; IFN-, interferon; T H 1/T H 2, T helper type 1 or 2; ↓, decrease; T reg , regulatory T cells; MDSCs, myeloid-derived suppressor cells; CR, complete remission; PR, partial remission; (number), number of patients in whom the designated immunological or clinical effect was observed.…”

Section: Figurementioning

confidence: 99%

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Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia

Acker

Versteven

Lichtenegger

et al. 2019

JCM

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Acute myeloid leukemia (AML) is a type of blood cancer characterized by the uncontrolled clonal proliferation of myeloid hematopoietic progenitor cells in the bone marrow. The outcome of AML is poor, with five-year overall survival rates of less than 10% for the predominant group of patients older than 65 years. One of the main reasons for this poor outcome is that the majority of AML patients will relapse, even after they have attained complete remission by chemotherapy. Chemotherapy, supplemented with allogeneic hematopoietic stem cell transplantation in patients at high risk of relapse, is still the cornerstone of current AML treatment. Both therapies are, however, associated with significant morbidity and mortality. These observations illustrate the need for more effective and less toxic treatment options, especially in elderly AML and have fostered the development of novel immune-based strategies to treat AML. One of these strategies involves the use of a special type of immune cells, the dendritic cells (DCs). As central orchestrators of the immune system, DCs are key to the induction of anti-leukemia immunity. In this review, we provide an update of the clinical experience that has been obtained so far with this form of immunotherapy in patients with AML.

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“…(Still earlier the difference Patients from treatment group in a continued remission between LAA during AML and ALL had been demonstrated [33][34][35]). Among the methods of immunotherapy there are great hopes from the use of peptide vaccines and derivates and modifications of dendritic cells [2,[36][37][38][39][40][41], however only few of those studies are concerned with AML [42][43][44][45]. All that serves as evidence of the justifiability of searching for rational methods of immunotherapy for recovery from AL.…”

mentioning

confidence: 99%

Disease-Free Remission Exceeding 37 Years in Patients Treated as Children for Acute Leukemia (AL) with Immunotherapy Using Viable (Cryopreserved) Allogeneic Leukemic Cells Pages 254-26

Bulycheva

2013

J. Can. Res. Updates

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At present time in spite of great achievements in modern chemotherapy of acute leukemia (AL) the issue of eradication of residual leukemic cells (MRD) is still relevant. Since 1971 we included specific immunotherapy in the treatment of children with acute lymphoblastic leukemia in remission using viable cryopreserved allogeneic leukemic cells. 67 children in remission were divided into 2 groups: 27 constituted the control group (only continued standard-forthat-time chemotherapy) and 40 children-the treatment which received immunotherapy in addition to standard chemotherapy. In 3 years all children in the control group relapsed. The median length of remission was 15 months. In the treatment group we observed stabilization of remission only in children over 7 years of age when immunization was initiated after 6 or more months of remission and in children younger than 7 if it was initiated after 1-1,5 years of remission. The median length of remission was 60 months which significantly exceeded (4 times) that parameter in the control group of children. Cytotoxic antibodies against leukemic cells appeared in the serum of effectively immunized children at a higher titer than against donor lymphocytes. Intrathecal administration of this hyperimmune serum to patients with neuroleukemia resistant to chemotherapy led to a sharp decrease in the amount of leukemic cells in the spinal fluid. After 5 years of remission (and 3-5 years of immunotherapy) all treatment in these patients was stopped. Out of 19 patients who received immunotherapy on time, 8 patients (42%) have been in event-free remission for 37 to 41 years (median-38 years) through the present time and enjoy high quality of life. Our results indicate that immunotherapy initiated during remission period of AL can lead to creation of anti-leukemic immunity with subsequent eradication of MRD and complete recovery.

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

Abstract: Immuno therapy with autologous DCs and CIK cells was found to be a promising candidate for treatment of AML in elderly patients.

Cited by 13 publications

References 26 publications

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review

Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia

Disease-Free Remission Exceeding 37 Years in Patients Treated as Children for Acute Leukemia (AL) with Immunotherapy Using Viable (Cryopreserved) Allogeneic Leukemic Cells Pages 254-26

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