Efficacy and Safety of Decitabine Combined with Modified CAG Regimen in Patients Aged ≥ 70 Years with Newly Diagnosed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical efficacy and safety of decitabine combined with modified CAG regimen (D-CAG regimen) in patients aged ≥70 years with newly diagnosed acute myeloid leukemia (AML).@*METHODS@#The clinical data of 59 AML patients (≥70 years old) who were newly diagnosed and treated in the Hematology Department of the First Affiliated Hospital of Nanjing Medical University from November 2010 to June 2021 were retrospectively analyzed.@*RESULTS@#Among the 59 AML patients, 28 were males and 31 were females, with a median age of 74 (70-86) years. The complete remission (CR) rate was 69.4% (34/49), and the median duration of CR was 10.7 (0.6-125.4) months after 2 courses of D-CAG treatment. According to the British Medical Research Council (MRC) classification, there was only one patient in the favorable-risk group, and the CR rate was 71.8% (28/39) in the intermediate-risk group, and 55.6% (5/9) in the adverse-risk group, respectively. There was no statistical difference in the CR rate between the intermediate-risk and adverse-risk group. Referring to ELN 2017 genetic risk classification, CR rate was 88.2% (15/17) in the favorable-risk group, 45.5% (5/11) in the intermediate-risk group, and 66.7% (14/21) in the adverse-risk group. There was no significant difference in CR rate between the favorable-risk and adverse-risk categories, but both were significantly higher than that in the intermediate-risk group (P <0.05). Next-generation sequencing (NGS) analysis showed that 11 gene mutations with a frequency of more than 10%, including TET2 mutation (35.6%), ASXL1 mutation (30.5%), NPM1 mutation (28.8%), FLT3-ITD mutation (27.1%), DNMT3A mutation (22.0%), IDH1 mutation (15.3%), CEBPA single mutation (13.6%), TP53 mutation (13.6%), IDH2 mutation (11.9%), RUNX1 mutation (11.9%), and NRAS mutation (10.2%). There were no statistical differences in mutation frequency of these 11 genes between CR group and non-CR group. Compared with normal karyotypes, patients with complex karyotypes were more likely to develop TP53 mutations (P <0.001), while FLT3-ITD and DNMT3A mutations were more likely to occur in patients with normal karyotypes (P =0.04, P =0.047). The median follow-up, overall survival (OS), and event-free survival (EFS) of all the patients was 11.7 (1.5-128.2) months, 12.3 (1.5-128.2) months, and 8.5 (1.5-128.2) months, respectively. The median OS and EFS of CR patients were 19.8 and 13.3 months, respectively, which were significantly longer than 6.4 and 5.7 months in patients experiencing treatment failure (P < 0.001, P =0.009). In regard to genes with mutation frequency >10%, there were no statistical differences in CR rate, median OS, and median EFS between mutated and wild-type patients by Chi-square test and survival analysis. Univariate analysis showed that age, hemoglobin, lactate dehydrogenase, cytogenetics and CR were factors affecting prognosis, while multivariate analysis showed that only CR failure was an independent adverse prognostic factor for OS. The major adverse reactions to D-CAG regimen were grade 3-4 myelosuppression, pulmonary infection, and fever (infection focus was not identified).@*CONCLUSION@#D-CAG regimen is safe and effective in the treatment of AML patients ≥70 years old, and can partially improve the prognosis of elderly and high-risk patients.

Clinical efficacy of low-dose decitabine and homoharringtonine combined with CAG regimen in treatment of acute myeloid leukemia / 白血病·淋巴瘤

Objective To evaluate the efficacy and safety of low-dose decitabine and homoharringtonine combined with CAG regimen (cytarabine, aclarubicin and recombinant human granulocyte colony-stimulating factor) (DHCAG regimen) in treatment of acute myeloid leukemia (AML). Methods Nineteen patients who were treated with DHCAG regimen in the 920th Hospital of Joint Logistics Support Force from July 2017 to June 2018 were retrospectively analyzed. Among them, 13 cases were newly diagnosed, 6 cases were ineffective or relapsed; 2 cases were elderly (≥60 years old); 15 cases had pulmonary infection before chemotherapy, and 4 cases had no lesions in the lungs when admitted to hospital. The remission rate and chemotherapy-related adverse reactions were analyzed. Results After 19 patients received one course of DHCAG regimen, 16 patients had complete remission, 1 patient had partial remission, 2 patients had no remission, and the overall response rate was 89.5% (17/19). Four patients with undetected lung disease before chemotherapy had no infection in the lungs after treatment. Among 15 patients with pulmonary infection before treatment, 1 patient died of pulmonary infection progress, the remaining 14 cases were grade 1-2 infection. 7 cases had bleeding, and 3 cases had nausea and vomiting, all of which were grade 1-2. Conclusion The remission rate of DHCAG regimen in treatment of AML is high, and its adverse reactions are tolerable.

Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC / 中华血液学杂志

Objective@#To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen.@*Methods@#A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m2 q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m2 for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m2 q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT).@*Results@#Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ2=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ2=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ2=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ2=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction.@*Conclusion@#The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.

Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC / 中华血液学杂志

Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.

Clinical analysis of low-dose decitabine combined with CAG regimen in treatment of elderly patients with acute myeloid leukemia and myelodysplastic syndromes patients with intermediate- or high-risk / 白血病·淋巴瘤

Objective To investigate the clinical value of low-dose decitabine (DAC) in elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients with intermediate-or high-risk. Methods Low-dose DAC (10 mg/d, 7 days) combined with CAG regimen were given to 19 elderly patients with AML and intermediate- or high-risk MDS patients. The efficacy and adverse reactions were evaluated after a course of treatment, and the patients were followed up for survival. Results After a course of treatment, 8 patients achieved complete remission (CR), 7 patients achieved partial remission (PR). After 4 courses of treatment, 68.4 % (13/19) of patients achieved CR, the overall response rate reached 78.9% (15/19). Fewer side effects were seen associated with chemotherapy. After 42 months of follow-up, there were 12 survival cases, the median survival time was 13.5 months (3-42 months). Conclusion Low-dose DAC combined with CAG regimen have a better efficacy, higher safety, and lower economic burden for elderly AML patients and intermediate- or high-risk MDS patients, which is beneficial to greatly improve patients' compliance.

Clinical outcome of decitabine combined with CAG regimen for treatment of acute myeloid leukemia ineligible for conventional chemotherapy / 白血病·淋巴瘤

Objective To investigate the safety and efficacy of decitabine combined with CAG regimen in treatment of acute myeloid leukemia (AML) ineligible for conventional chemotherapy. Methods The data of 20 cases with AML ineligible for conventional chemotherapy from January 2013 to May 2015 were retrospectively analyzed. Decitabine combined with CAG regimen was used during induction therapy. The primary induction regimen was used 26 times after remission, the standard 3+7 regimen were used 7 times, and intermediate-dose cytarabine were used 3 times. The total course of treatment included 2-8 cycles. Results All of the 20 patients completed the first cycle of induction therapy, including 11 cases of complete remission (CR), 5 cases of partial remission and no response in 4 cases, and the overall response rate (ORR) was 80 % (16/20). ORR was 69.2 % (9/13) and 100.0 % (7/7) in high-risk group and middle-low risk group respectively. ORR was 60.0%(6/10) in AML evolving from MDS. 8 patients were infected during the induction therapy and the infection rate was 40.0% (8/20). 2 patients were died of pulmonary infection. The median number of suspended red blood cell and platelet infused were (9.1±5.7) U and (57.5±51.9) U respectively. Neutrophil recovery time was (8.7±5.6) days during induction therapy. All patients were followed up for at least 1 year, and 12 cases were dead. Overall survival rate was 85.0%at 3 months, 80.0%at 6 months, and 40.0%at 1 year. While in 12 CR patients relapse-free survival rate was 75.0%at 3 months, 75.0%at 6 months,and 65.6%at 1 year respectively. Conclusion Decitabine combined with CAG regimen with high remission rate and well tolerance, can be used as a first therapy for AML ineligible for conventional chemotherapy.

Clinical Efficacy of CAG Regimen Used in 35 Cases of Newly Diagnosed Acute Myeloid Leukemia in Elder-ly Patients / 中国药师

To study the efficacy of CAG regimen used in 35 cases of newly diagnosed acute myeloid leukemia in elder-ly patients. Methods:Totally 35 cases of elderly patients with acute myeloid leukemia were randomly divided into two groups. The pa-tients in the control group (15 cases) were treated with standard chemotherapy treatment, while the CAG regimen group (20 cases) was treated with CAG regimen (cytarabine, aclarubicin and granulocyte colony-stimulating factor). After one treatment course, the chemotherapy efficacy was observed, and the neutrophil and platelet recovery time and the incidence of adverse reactions in the two groups were compared. Results:The treatment efficacy of the CAG regimen group was 90%, which was higher than that of the control group (60%, P<0. 05). The neutrophil and platelet recovery time of the CAG regimen group was significantly shorter than that of the control group (P<0. 05). The incidence of adverse reactions in CAG regimen group was much lower than that of the control group(P<0. 05). Conclusion:The efficacy of CAG regimen used in the 35 cases of newly diagnosed acute myeloid leukemia in elderly pa-tients is promising, which can effectively control the progression of the disease and accelerate blood cell recovery with high safety.

Clinical analysis of decitabine combine with different regimens in the treatment of elderly patients with acute myeloid leukemia / 白血病·淋巴瘤

Objective To investigate the therapeutic effects and adverse reactions of decitabine combined with IA or CAG regimen in the treatment of elderly patients with acute myeloid leukemia.Methods A retrospective analysis was made to observe the therapeutic effects and adverse reactions of 47 elderly patients with acute myeloid leukemia,who were divided into DAC+IA group (17 cases) and DAC+CAG group (28 cases) according to the different chemotherapy.Results In DAC+IA group,the rate of complete remission was 29.4 ％ (5/17),the rate of partial remission was 35.3 ％ (6/17),the effective rate was 64.7 ％ (11/17).In DAC+CAG group,the rate of complete remission was 26.7 ％ (8/30),the rate of partial remission was 30.0 ％ (9/30),the effective rate was 56.7 ％ (17/30),the difference between the two groups was not statistically significant (x2 =0.227,P =0.716).In DAC+IA group the median remission time and the median suvival time were 4.0 and 8.1 months,respectively.And they were 4.0 and 8.1 months,respectively,in DAC+CAG group.No significant difference was showed between the two groups (P value was 0.835,0.266,respectively).Conclusions Compared with decitabine combined with CAG regimen,decitabine combined with IA regimen has similar effect and can be well tolerated.Accordingly,decitabine combined with IA regimen can be used as first-line treatment for elderly patients with acute myeloid leukemia.

An evaluation of therapeutic effect of idarubicin combined with CAG regimen on previously untreated elderly patients with acute myeloid leukemia / 中国中西医结合急救杂志

10.3969/j.issn.1008-9691.2013.03.017

Outcomes and survival analysis of patients with AML and high risk MDS treated by CAG regimen / 上海交通大学学报（医学版）

Objective To evaluate the clinical efficacy and adverse effects of CAG regimen in treatment of primary, refractory and relapsed acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS), and analyse the factors influencing long-term survival. Methods Sixty-one patients with AML ( primary, n = 27; refractory, n = 18; relapsed, n = 16) and 9 patients with MDS were treated with CAG regimen. Examinations on liver and renal function, electrocardiogram and bone marrow cytology were performed before and after treatment, and adverse effects of CAG were observed. Short-term efficacy was evaluated based on clinical manifestation, peripheral blood and bone marrow cytologic examinations. Patients were followed up, overall survival ( OS) and disease free survival ( DFS) were analysed, and long-term efficacy of CAG regimen was evaluated. The factors influencing long-term survival were analysed by Log-rank test of survival curve. Results After a course of treatment by CAG regimen, the total effective rate was 71% , and 34 patients (49%) experienced complete remission. The median time of follow up was 45 months, the median OS was 28 months, and the median DFS was 23 months. Age, level of lactate dehydrogenase (LDH), remission condition after a course of treatment by CAG regimen and adoption of HD-Ara-C regimen as consolidation treatment were influencing factors for OS and DFS. The dominant clinical adverse effects were bone marrow depression, with 13 d as the median duration of agranulocytosis ( neutrophil <0.5 ×10~9/L) and 9 d as the median duration of thrombocytopenia (platelet <20 ×10~9/L). Conclusion CAG regimen may lead to favourable therapeutic effects in treatment of primary, refractory and relapsed AML and high risk MDS, and may yield less adverse effects and better long-term therapeutic effects. Age, level of LDH, remission condition after a course of treatment and adoption of HD-Ara-C regimen as consolidation treatment are dominant influencing factors for survival.