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Patients with AML-MRC benefit from decitabine in combination with low-dose G-CSF, cytarabine and aclarubicin: A single center cohort study.

ABSTRACT: Patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are insensitive to conventional chemotherapy and, therefore, have a poor prognosis. To evaluate the clinical efficacy and safety of low-dose decitabine in combination with small-dose CAG regimen (D-CAG regimen) in treating AML-MRC, a total of 80 patients with newly diagnosed AML-MRC from September 2015 to January 2020 in our center were included in the study. Amongst these patients, 43 and 37 patients received two courses of the D-CAG and CAG regimens, respectively. The complete remission (CR) and complete remission with incomplete blood count recovery (CRi) rate in the D-CAG group was higher than that of the CAG group (62.2% vs. 48.8%, P = 0.013). Among patients with less than 9 months of myelodysplastic syndrome (MDS) history and poor karyotypes, the (CR+CRi) rate of the D-CAG group was statistically higher than that of the CAG group. Except for patients receiving hematopoietic cell transplantation, among patients with less than 9 months of MDS history, the D-CAG group showed a better probability of overall survival than the CAG group did. In conclusion, patients with AML-MRC may benefit from the D-CAG regimen as an induction therapy, especially patients with less than 9 months of MDS history or with poor karyotypes.

SUBMITTER: Liu J

PROVIDER: S-EPMC9594112 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Patients with AML-MRC benefit from decitabine in combination with low-dose G-CSF, cytarabine and aclarubicin: A single center cohort study.

Liu Jing J Liu Xiaohong X Jia Jinsong J Gong Lizhong L Lu Shengye S Wang Jing J Huang Xiao-Jun XJ Jiang Hao H

Leukemia research reports 20221019

Patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) are insensitive to conventional chemotherapy and, therefore, have a poor prognosis. To evaluate the clinical efficacy and safety of low-dose decitabine in combination with small-dose CAG regimen (D-CAG regimen) in treating AML-MRC, a total of 80 patients with newly diagnosed AML-MRC from September 2015 to January 2020 in our center were included in the study. Amongst these patients, 43 and 37 patients received two ...[more]

PMID: 36304522

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Project description:In the present study, the ability of the proteasome inhibitor bortezomib (BZ), an oxidative stress-inducing agent, to sensitize acute myeloid leukemia (AML) cells to decitabine (Dacogen®, DAC; a DNA methyltransferase inhibitor), in terms of cell viability and differentiation, was investigated. Kasumi-1 AML (M2) cells were treated with low-dose DAC (10, 50, 100, 200 or 400 nΜ), with or without BZ (10 nM). Apoptosis and the cell cycle were evaluated after 24 h of treatment through fluorescence-assisted cell sorting (FACS) with Annexin V/propidium iodide and DAPI staining, respectively. The expression levels of CD193, CD11b, CD13, CD14, CD15, CD16 and CD117 surface differentiation markers were evaluated by FACS after 6 days of treatment. The results indicated significant alterations in cell death and cell cycle phases in Kasumi-1 cells following DAC and BZ combination treatment compared to untreated cells and cells with single treatments. Low-dose DAC/BZ combinations significantly enhanced apoptosis and decreased the population of live Kasumi-1 cells, with 100 and 200 nM of DAC and 10 nM BZ appearing to have the most potent synergistic effect according to a combination index. Furthermore, cell cycle profiling revealed that DAC/BZ treatment synergistically led to G0/G1- and G2/M-phase arrest. By contrast, DAC appeared to promote monocytic and granulocytic differentiation of Kasumi-1 cells more effectively alone than in combination with BZ. BZ acted synergistically with low-dose DAC in vitro, leading to enhanced apoptosis and G0/G1- and G2/M-phase arrest in AML cells, hence prohibiting either DNA synthesis or mitosis. Although further in vivo investigation is necessary, these results provide a strong rationale for the implementation of a combination treatment with DAC and bortezomib in AML therapy, followed by DAC alone, which may achieve better clinical responses and possibly partially overcome the frequently encountered DAC resistance of patients with AML.

Dataset Information

Patients with AML-MRC benefit from decitabine in combination with low-dose G-CSF, cytarabine and aclarubicin: A single center cohort study.

Publications

Patients with AML-MRC benefit from decitabine in combination with low-dose G-CSF, cytarabine and aclarubicin: A single center cohort study.

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