OBJECTIVETo explore the effects of beta-elemene combined with aclarubicin on the induction of HL-60 cell apoptosis and its mechanisms in antileukemia therapy.

METHODSHL-60 cells were treated for 20 hours with different dose of aclarubicin (0.05, 0.10, 0.25 microg/ml) or with different concentrations of beta-elemene (10, 20, 40 microg/ml) in the presence or absence of aclarubicin (0.10 microg/m). The apoptotic rate was analyzed by flow cytometry (FCM), the productions of PGE2 in culture supernatants was detected by competitive ELISA and the expressions of COX-2 and NF-kappaB activity in HL-60 cells by Western blot.

RESULTSLower concentration of aclarubicin (0.05, 0.10 microg/ml) didn't affect apoptotic rate, and COX-2, NF-kappa B and PGE2 expression on HL-60 cells. Combined treatment of beta-elemene and aclarubicin (0.10 microg/ml) enhanced the apoptotic effect and down-regulated COX-2, NF-kappaB and PGE2 expressions. There was a positive correlation between the effects and beta-elemene concentrations.

CONCLUSIONbeta-elemene enhances aclarubicin-mediated apoptotic effect, down-regulation of COX-2 and their inducing products PGE2 in HL-60 cells by suppressing activitation of NF-kappaB.

Aclarubicin ; Apoptosis ; drug effects ; Cell Line, Tumor ; Down-Regulation ; HL-60 Cells ; Humans ; NF-kappa B ; metabolism

The objective of study was to observe the efficacy and adverse events of modified CAG regimen in treating patients with relapsed acute myeloid leukemia. CAG regimen with prolongation of aclarubicin up to 7 days were used to treat 17 cases of relapsed acute myeloid. After 1 course of chemotherapy, the efficacy and adverse events were evaluated, patients who did not achieve remission were excluded from this regimen, patients who achieved remission were continuously given 1 course of CAG regimen. The results showed that out of 17 case 8 patients achieved complete remission (CR, 47.06%) and 5 patients achieved partial remission (PR, 29.14%). Most of these cases had slight adverse events which mainly were marrow suppression that could be tolerated, overall survival was 76.47%. In conclusion, treatment for relapsed acute myeloid leukemia with modified CAG regiment is safe and effective, and can provide conditions for allo-hematopoietic stem cell transplantation, but its long term efficacy needs to further study.
Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Treatment Outcome

OBJECTIVETo investigate the efficacy and toxicity of modified FLAG and CAG on relapsed or refractory acute myeloid leukemia (AML).

METHODSSixty-one patients with relapsed or refractory AML were divided into modified FLAG or CAG group. In modified FLAG group: G-CSF 200 μg·m⁻²·d⁻¹ on days 0-5; fludarabine 30 mg·m⁻²·d⁻¹ on days 1-5; Ara-C 1.0 g·m⁻²·d⁻¹ on days 1-5. In CAG group: Ara-C 10 mg·m⁻²·12 h⁻¹ on days 1-14, aclarubicin 20 mg/d on days 1-4, G-CSF 200 μg·m⁻²·d⁻¹ on days 0 1-14.

RESULTSThe complete response (CR) rate was 43% (12/28) and the partial response (PR) rate 18% (5/28) with the overall response (OR) rate of 61% in modified FLAG group. CR rate was 21% (7/33) and PR rate 15% (5/33) with OR rate of 36% in CAG group. There was significant statistical difference between two groups (P<0.05). The main toxicities of these groups were myelosupression and infection. The infection rate was 68% (19/28) in modified FLAG group (twenty-two patients were treated in the sterile laminar flow ward duing neutropenic period), treatment related mortality (TRM) in modified FLAG group was 7%; The infection rate was 55% (18/33) in CAG group (no patient was treated in the sterile laminar flow ward), TRM in CAG group was 3%. There was no significant statistical difference in two groups (P>0.05).

CONCLUSIONModified FLAG was effective for relapsed or refractory AML. The supportive cares to strengthen infection-controlled measures and shorten the period of bone marrow suppression produced the additional effect. CAG regimen has low adverse reactions and could be individualized to elder or weak patients.

Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence

Abstract　　 Demethylating agents (HMAs) hold an important status in therapy for elderly acute myeloid leukemia, who are not eligible for intensive chemotherapy (ICT). Beyond the edge of monotherapy, domestic and foreign scholars have carried out a lot of studies on combination strategies, such as HMAs with low-intensity therapy (G-CSF, low-dose cytarabine and aclarubicin, CAG), with targeted therapy (BCL-2 inhibitor), with immunotherapy (immune checkpoint inhibitors, ICI), and with other epigenetic therapys (isocitrate dehydrogenase or histonedeacetylase inhibitor）. Some of these researches have obtained positive results and discussed the mechanisms of combination strategies besides. In this review, the combination of HMAs with other drugs are summraized briefly.
Aclarubicin ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Isocitrate Dehydrogenase ; Leukemia, Myeloid, Acute

Aclarubicin ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Cytarabine ; Female ; Granulocyte Colony-Stimulating Factor ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Young Adult

OBJECTIVETo observe the clinical safety and efficacy of decitabine in patients of acute myeloid leukemia and myelodysplastic syndromes (MDS/AML).

METHODSTotally 79 patients with MDS/AML were divided into three groups: (1)Treated with decitabine alone (20 mg/m² for 5 days). (2) Combination of decitabine with half dose CAG chemotherapy (Acla 20 mg qod×3 d, Ara-C 10 mg/m² q12 h×7 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). (3)Combination of decitabine with CAG chemotherapy (Acla 20 mg qod×4 d, Ara-C 10 mg/m² q12 h×14 d, G-CSF 300 μg/d, the dose of G-CSF adjust to the amount of blood routine). We observed complete remission (CR) rate, overall response rate (ORR) and overall survival (OS) of the three groups; meanwhile, we analyzed the factors relevant to decitabine efficacy and the prognosis.

RESULTSORR in the three groups were 53.3%, 56.5% and 69.2% respectively, with no statistically significant differences (P>0.05). Due to the last follow-up at 2014.04.01, 20 patients still survived, 45 died, 14 were lost to follow-up. The 5-year cumulative survival rate of 79 patients was 25.3%, the 2-year survival were of the three groups were 34.8%, 24.8 and 29.2% respectively with no statistically significant differences (P>0.05). Adverse events of infection and bleeding were mainly caused by decitabine. Grade 3 to 4 hematological toxicities were observed in 72 cases with the average time for the lack of granulocytes as 14.8 days. 59 patients experienced infectious events, including grade 3 or 4 infections in 14 cases, grade 1 or 2 infections in 45 cases. There were no statistically significant differences (P>0.05) among the three groups in terms of infection rates, bleeding rates, duration of neutrophenia, mean MAP transfusion and mean platelet transfusion. 79 patients were safely through bone marrow suppression by anti-infective and supportive treatment without treatment-related deaths.

CONCLUSIONTreating MDS/AML with decitabine alone, in combination with half or one course CAG regimen produced high efficacy. ORR of the combination of decitabine with one course CAG regimen was relatively higher. Three groups of patients were all well tolerated.

Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Azacitidine ; analogs & derivatives ; Cytarabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Myelodysplastic Syndromes ; drug therapy

Aclarubicin ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Recurrence

OBJECTIVE: To systematically evaluate the efficacy and safety of DCAG regimen for treating the intermediate or high risk MDS and AML. METHODS: PubMed, EMbase, The Cochrane Library, WanFang Data and CNKI databases were searched to collect randomized controlled trials (RCTs) of decitabine combined with CAG regimen for intermediate or high risk MDS and AML from inception to March, 2018. The quality of each RCT was evaluated by the Cochrane collaboration´s tool for assessing the risk of bias.Then, the data were analyzed by using RevMan 5.3. RESULTS: Twenty-four RCTs were included in the meta-analysis, containing 1 557 patients with intermediate or high-risk MDS and AML, of whom 594 were AML patients and 590 were MDS patients. The patients treated with the DCAG regimen were enrolled in DCAG group, and the patients treated with single-agent decitabine or CAG regimen were enrolled in control group. RESULTS: The results of meta-analysis showed that compared with other therapies, the complete remission rate of DCAG regimen in patients with intermediate or high-risk MDS and AML was high (RR=1.63，95% CI=1.43-1.85，P＜0.000 01), and the overall response rate was also high (RR=1. 35，95% CI=1.24-1.46，P＜0.000 01); Subgroup analysis results showed that DCAG regimen was better than CAG regimen in the complete remission rate (RR=1.71，95% CI=1.49-1.97，P＜0.000 01), and slightly better than single-agent decitabine group (RR=1.43，95% CI=1.08-1.91，P=0.01). In terms of adverse reactions, there was no statistically significant difference in the rates of myelosuppression, pulmonary infection, gastrointestinal reactions, and bleeding events between the 2 groups (P＞0.05). CONCLUSION DCAG regimen has significant efficacy in the treatment of intermediate or high-risk MDS and AML, and is superior to CAG regimen and single-agent dicitabine regimen. As compared with control group, there was no significant difference in adverse events. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above mentioned conclusion.
Aclarubicin ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; Decitabine ; Granulocyte Colony-Stimulating Factor ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Myelodysplastic Syndromes ; drug therapy

The development of multidrug-resistant tumor cell population is a major problem in the chemotherapy of human cancer. These cells are often cross resistant to unrelated drugs and the precise mechanisms of multidrug resistant phenotype of tumor cells has not been fully elucidated. Cisplatin resistant tumor cell (SNU-1/Cis₅) was induced from human stomach cancer cell line (SNU-1) in vitro. Growth profiles of survival cells were observed during 5 days by thiazolyl blue (MTT) assay. To investigate the cross resistance of various anticancer drugs in SNU-1 and SNU-1/Cis5, We compared the value of IC₅₀-drug concentration at 50% survival of control and gained relative resistances (RR). The RR for SNC-1/Cis₅ were as follows; vinblastine, > 43.0; epirubicin, 22.9; dactinomycin, 16.0; etoposide, 15.0; vincristine, 9.2; adriamycin, 5.7; aclarubicin, 5.3. But 5-fluorouracil, methotrexate, daunorubicin have not cross resistance with cisplatin. Resistant inhibition values of 10µM verapamil for SNU-1/Cis₅ were as follows; vincristine, 13.1; epirubicin, 10.0; etoposide, 6.3; vinblastine, 4.4; dactinomycin, 3.6; daunorubicin, 2.4. Membrane proteins of 51,400 and 81,300 daltons were identified by radioiodination with SDS-PAGE, which might represented the drug resistance.
Aclarubicin ; Cell Line ; Cisplatin* ; Dactinomycin ; Daunorubicin ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple* ; Drug Therapy ; Electrophoresis, Polyacrylamide Gel ; Epirubicin ; Etoposide ; Fluorouracil ; Humans* ; In Vitro Techniques ; Membrane Proteins ; Methotrexate ; P-Glycoprotein ; Phenotype ; Stomach Neoplasms* ; Stomach* ; Verapamil* ; Vinblastine ; Vincristine

To evaluate the efficacy and toxicity of low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (G-CSF) protocol for patients with relapsed acute myeloid leukemia (AML). A total of fifty relapsed patients have been enrolled, including 13 early relapsed and 37 late relapsed. 24 patients were male and 26 were female, with age ranging from 15 to 69 (median 47) years. Out of them, 7 patients relapsed after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), 3 patients relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT), 25 patients relapsed after received regimens including high dose cytarabine and 15 patients relapsed after CR or stopping chemical therapy themself in course of consolidatory therapy. 30 relapsed patients received CAG regimen, and 20 patients (control group) received an anthracycline in combination with cytarabine. The results indicated that after one course, the complete remission (CR) rate was 46.7% (14/30), the CR rate after allo-PBSCT was 50% (3/6), the early death rate was 3.3% in CAG group; and CR rate was 30% (6/20) and the early death rate was 15% in control group. Myelosuppression was mild to moderate, and no severe nonhematologic toxicity was observed in two groups. The overall median times in CAG group and control group were 22 and 19 months respectively. In conclusion, CAG regimen as the induction therapy is effective and well tolerable with low side effects for relapsed patients who had received high dose cytarabine, auto-PBSCT or allo-PBSCT.
Aclarubicin ; administration & dosage ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; administration & dosage ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult