1.Clinical research of modified CAG regimen for the treatment of relapsed acute myeloid leukemia.
Jun-Yue CHAI ; Wen-Qi ZHENG ; Na WEI
Journal of Experimental Hematology 2009;17(4):1061-1063
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
2.The comparative study of the effects between modified FLAG and CAG on relapsed or refractory acute myeloid leukemia.
Tao WANG ; Liangming MA ; Qiujuan ZHU ; Rong GONG ; Zhilin GAO ; Weiwei TIAN
Chinese Journal of Hematology 2014;35(11):966-969
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
3.beta-elemene enhances aclarubicin-induced apoptotic effect in HL-60 cells and its mechanism..
Cui-Ping ZHENG ; Xiang-Min TONG ; Hang-Ping YAO ; Jun YANG ; Jie XU ; Xiao-Ping CAI ; Zheng LIU
Chinese Journal of Hematology 2009;30(12):821-824
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
4.Research Advances on Combination Strategies of Demethylating Agents for Elderly Acute Myeloid Leukemia--Review.
Journal of Experimental Hematology 2019;27(4):1339-1343
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
6.The clinical efficacy of the patients of acute myeloid leukemia and myelodysplastic syndromes treated with decitabine alone, combined with half or one couse of CAG regimen.
Su GAO ; Huiying QIU ; Zhengming JIN ; Xiaowen TANG ; Zhengzheng FU ; Xiao MA ; Yue HAN ; Suning CHEN ; Aining SUN ; Depei WU
Chinese Journal of Hematology 2014;35(11):961-965
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
8.Efficacy and Safety of Decitabine Combined with CAG (Cytarabine, Aclarubicin, G-CSF) for Patients with Intermediate or High Risk Myelodysplastic Syndrome and Acute Myeloid Leukemia: a Meta-Analysis.
Jing-Ling ZHANG ; Ying-Ping CAO ; Jing-Gang LI
Journal of Experimental Hematology 2019;27(2):494-503
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
9.Efficacy analysis of CAG priming regimen combined with talidomide, interferon and interleukin 2 as the induction therapy for relapsed refractory acute myeloid leukemia.
Yingling ZU ; Yanli ZHANG ; Jian ZHOU ; Huifang ZHAO ; Ruirui GUI ; Zhen LI ; Mengjuan LI ; Xudong WEI ; Yongping SONG
Chinese Journal of Hematology 2016;37(4):334-336
Aclarubicin
;
therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols
;
therapeutic use
;
Cytarabine
;
therapeutic use
;
Granulocyte Colony-Stimulating Factor
;
therapeutic use
;
Humans
;
Interferons
;
therapeutic use
;
Interleukin-2
;
therapeutic use
;
Leukemia, Myeloid, Acute
;
drug therapy
;
Recurrence
;
Remission Induction
;
Thalidomide
;
therapeutic use
10.Efficacy of HAA regimen in the treatment of 64 patients with refractory/relapsed acute myeloid leukemia.
Cuihua FAN ; Wenjuan YU ; Wenyuan MAI ; Haitao MENG ; Wenbin QIAN ; Hongyan TONG ; Jian HUANG ; Liping MAO ; Shanshan SUO ; Jie JIN
Chinese Journal of Hematology 2016;37(2):100-104
OBJECTIVETo evaluate the efficacy and safety of the HAA regimen (homoharringtonine,cytarabine and aclarubicin)as salvage chemotherapy in the treatment of refractory/relapsed acute myeloid leukemia (AML).
METHODSWe retrospectively analyzed 64 patients with refractory/relapsed AML who received the HAA regimen as salvage chemotherapy. The complete remission (CR)rate was analyzed. Kaplan-Meier method was used to estimate overall survival (OS) and relapse free survival (RFS), and the differences were compared by Log-rank test.
RESULTSThe overall CR rate was 70.1%, and 67.1% of the patients attained CR after the first induction course. The early death rate was 0. The median follow-up time was 61 (range:6-120) months. The estimated 3-year OS rate was 46.8% and the estimated 3-year RFS rate was 42.8%. The CR rates of patients with favorable/intermediate and unfavorable cytogenetics were 76.4% and 33.3%, respectively. The 3-year OS of favorable/intermediate and unfavorable group were 53.7% and 10.0%, respectively. The median survival time of unfavorable group was only 8 months. The side effects associated with the HAA regimen were tolerable, in which the most common toxicities were myelosuppression and infection.
CONCLUSIONHAA regimen is associated with a higher rate of CR and longer-term survival and its toxicity can be tolerated. The regimen is suitable for refractory/relapsed AML patients with favorable or intermediate risk .
Aclarubicin ; analogs & derivatives ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; therapeutic use ; Harringtonines ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Recurrence ; Remission Induction ; Retrospective Studies ; Salvage Therapy ; Survival Rate