Clinical therapeutic efficacy of decitabine contained chemotherapies on 101 patients with relapsed or refractory acute myeloid leukemia_West China Medical Journal

Authors：

ZHANG Nanchen , WANG Huifang , WU Xia , DENG Jili ,  GONG Yuping

Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

GONG Yuping, Email: gongyuping2010@aliyun.com

Keywords：

Decitabine; Acute myeloid leukemia; Complete remission rate; Adverse reaction

DOI：

10.7507/1002-0179.201809138

Video：

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Objective To analyze the clinical efficacy of decitabine contained chemotherapy regimens in the treatment of relapsed or refractory acute myeloid leukemia (AML) patients.Methods A total of 101 patients with relapsed or refractory AML from May 2014 to December 2017 were collected retrospectively. Three schemes with a relatively larger number of users were included: 15 cases were treated with decitabine monotherapy (DAC regime); 37 cases were treated with decitabine, anthracycline antibiotic, and cytarabine (D-DA regime); and 49 cases were treated with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulatingfactor (G-CSF) (D-CAG regimen). The remission rate, blood products support strength, degree and duration of bone marrow suppression, adverse reaction, and survival time were compared.Results The complete remission (CR) rates of DAC, D-DA and D-CAG regimen group were 40.0%, 48.6%, and 71.4%, respectively; the overall respond rates (ORR) were 46.7%, 54.1%, and 79.6%, respectively. The ORR in D-CAG regimen group was higher than those in the other two groups (P<0.017). The dosage of G-CSF in D-CAG regimen group were lower than those in DAC regimen group [ (1 363.0±1 037.9) vs. (2 517.0±1 163.4) μg, P<0.05]; the mean number of erythrocyte transfusion and the dosage of G-CSF were lower than those in D-DA regimen group [(6.7±4.0) vs. (14.8±10.1) U, P<0.05; (1 363.0±1 037.9) vs. (2 786.0±1474.0) μg, P<0.05]; the time to the suppression of hemoglobin and platelet in D-CAG regimen group were later than those in D-DA regimen group [(11.5±2.6) vs. (8.8±2.5) days, P=0.007; (10.9±2.6) vs. (7.6±2.5) days, P=0.002]; the time to the suppression of platelet was later than that in DAC regimen group [(10.9±2.6) vs. (7.6±1.6) days, P=0.003]. There was no statistically significant difference in the incidence of adverse reations among the three group (P>0.05). The median overall survival of D-CAG regimen group was longer than that in DAC regimen group (11.6 vs. 8.8 months, P=0.013).Conclusion Among the three chemotherapy regimens containing decitabine, the CR and ORR of D-CAG regimen are higher, the tolerance is better, and further promotion can be attempted in qualified medical institutions.

Citation： ZHANG Nanchen, WANG Huifang, WU Xia, DENG Jili, GONG Yuping. Clinical therapeutic efficacy of decitabine contained chemotherapies on 101 patients with relapsed or refractory acute myeloid leukemia. West China Medical Journal, 2019, 34(4): 363-369. doi: 10.7507/1002-0179.201809138 Copy

1.	Carella AM, Cascavilla N, Greco MM, et al. Treatment of " poor risk” acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single center study. Leuk Lymphoma, 2001, 40(3-4): 295-303.
2.	Kantarjian H, Ravandi F, O’brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood, 2010, 116(22): 4422-4429.
3.	Quintás-Cardama A, Ravandi F, Liu-Dumlao T, et al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood, 2012, 120(24): 4840-4845.
4.	Ritchie EK, Feldman EJ, Christos PJ, et al. Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia. Leuk Lymphoma, 2013, 54(9): 2003-2007.
5.	Nieto M, Demolis P, Behanzin E, et al. The European medicines agency review of decitabine (dacogen) for the treatment of adult patients with acute myeloid leukemia: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist, 2016, 21(6): 692-700.
6.	Cazzola M. Introduction to a review series: the 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues. Blood, 2016, 127(20): 2361-2364.
7.	Mesa RA, Jamieson C, Bhatia R, et al. NCCN guidelines insights: myeloproliferative neoplasms, version 2. 2018. J Natl Compr Canc Netw, 2017, 15(10): 1193-1207.
8.	中华医学会血液学分会, 中国医师协会血液科医师分会. 中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016 年版). 中华血液学杂志, 2016, 37(5): 353-359.
9.	Veatch JR, Sandhu V, Becker PS, et al. The NCI common toxicity criteria and treatment-associated mortality in acute myeloid leukemia. Blood, 2013, 122(2): 293-294.
10.	Szer J. The prevalent predicament of relapsed acute myeloid leukemia. Hematology, 2012, 2012(1): 43-48.
11.	王利军, 丁洁, 朱成英, 等. FLAG 方案治疗难治复发急性髓系白血病的临床研究. 中国实验血液学杂志, 2016, 24(1): 19-24.
12.	Kantarjian HM, Erba HP, Claxton D, et al. PhaseⅡstudy of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol, 2010, 28(4): 549-555.
13.	Thol F, Schlenk RF, Heuser M, et al. How I treat refractory and early relapsed acute myeloid leukemia. Blood, 2015, 126(3): 319-327.
14.	Qu Y, Siggens L, Cordeddu L, et al. Cancer-specific changes in DNA methylation reveal aberrant silencing and activation of enhancers in leukemia. Blood, 2017, 129(7): e13-e25.
15.	Yang J, Xiao X, Li R, et al. Hypermethylation of CpG sites at the promoter region is associated with deregulation of mitochondrial ATPsyn-β and chemoresistance in acute myeloid leukemia. Cancer Biomark, 2016, 16(1): 81-88.
16.	章红涛, 冯雅青, 赵芳, 等. 地西他滨联合半量 CAG 方案治疗复发难治急性髓系白血病效果观察. 白血病·淋巴瘤, 2018, 27(7): 404-406, 409.
17.	朱成英, 刘世研, 牛建花, 等. 地西他滨联合改良 CAG 方案治疗复发、难治型急性髓系白血病的临床研究. 中国实验血液学杂志, 2015, 23(1): 88-93.
18.	高然, 张蕊, 于锦香, 等. 地西他滨联合半量 CAG 方案治疗老年性及复发难治性急性髓细胞白血病的疗效分析. 中国医科大学学报, 2013, 42(6): 515-517.
19.	耿素红, 王微娜. 地西他滨联合改良 CAG 方案治疗复发、难治性急性髓系白血病的疗效观察. 中国医院用药评价与分析, 2018, 18(4): 509-510, 513.
20.	Schroeder T, Rautenberg C, Haas R, et al. Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation. Int J Hematol, 2018, 107(2): 138-150.
21.	Daver N, Kantarjian H, Ravandi F, et al. A phaseⅡ study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia, 2016, 30(2): 268-273.
22.	Khan N, Hantel A, Knoebel RW, et al. Efficacy of single-agent decitabine in relapsed and refractory acute myeloid leukemia. Leuk Lymphoma, 2017, 58(9): 1-7.
23.	汪梅花, 赵康, 葛繁梅. 去甲基化药物联合 CAG 方案治疗老年白血病或难治复发性白血病疗效观察及对 VEGF、bFGF 的影响研究. 临床和实验医学杂志, 2018, 17(3): 311-314.
24.	杨柳, 葛健, 夏瑞祥. AML 对柔红霉素的耐药性与 TET2 基因突变的相关性. 安徽医科大学学报, 2018, 53(2): 242-246.
25.	姜艳红, 陈光意, 盛家和, 等. 外周血原始细胞比例高于骨髓的初治原发 AML 的临床特征及其与患者第一次完全缓解的关系. 实用医学杂志, 2018, 34(9): 1545-1549.
26.	苏龙, 李薇, 崔久巍, 等. 正常核型急性髓系白血病 NPM1、FLT3-ITD 突变与外周血白细胞数及骨髓原始细胞百分比相关性研究. 中国实验血液学杂志, 2013, 21(3): 571-575.

1. Carella AM, Cascavilla N, Greco MM, et al. Treatment of " poor risk” acute myeloid leukemia with fludarabine, cytarabine and G-CSF (flag regimen): a single center study. Leuk Lymphoma, 2001, 40(3-4): 295-303.
2. Kantarjian H, Ravandi F, O’brien S, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood, 2010, 116(22): 4422-4429.
3. Quintás-Cardama A, Ravandi F, Liu-Dumlao T, et al. Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood, 2012, 120(24): 4840-4845.
4. Ritchie EK, Feldman EJ, Christos PJ, et al. Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia. Leuk Lymphoma, 2013, 54(9): 2003-2007.
5. Nieto M, Demolis P, Behanzin E, et al. The European medicines agency review of decitabine (dacogen) for the treatment of adult patients with acute myeloid leukemia: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist, 2016, 21(6): 692-700.
6. Cazzola M. Introduction to a review series: the 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues. Blood, 2016, 127(20): 2361-2364.
7. Mesa RA, Jamieson C, Bhatia R, et al. NCCN guidelines insights: myeloproliferative neoplasms, version 2. 2018. J Natl Compr Canc Netw, 2017, 15(10): 1193-1207.
8. 中华医学会血液学分会, 中国医师协会血液科医师分会. 中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016 年版). 中华血液学杂志, 2016, 37(5): 353-359.
9. Veatch JR, Sandhu V, Becker PS, et al. The NCI common toxicity criteria and treatment-associated mortality in acute myeloid leukemia. Blood, 2013, 122(2): 293-294.
10. Szer J. The prevalent predicament of relapsed acute myeloid leukemia. Hematology, 2012, 2012(1): 43-48.
11. 王利军, 丁洁, 朱成英, 等. FLAG 方案治疗难治复发急性髓系白血病的临床研究. 中国实验血液学杂志, 2016, 24(1): 19-24.
12. Kantarjian HM, Erba HP, Claxton D, et al. PhaseⅡstudy of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol, 2010, 28(4): 549-555.
13. Thol F, Schlenk RF, Heuser M, et al. How I treat refractory and early relapsed acute myeloid leukemia. Blood, 2015, 126(3): 319-327.
14. Qu Y, Siggens L, Cordeddu L, et al. Cancer-specific changes in DNA methylation reveal aberrant silencing and activation of enhancers in leukemia. Blood, 2017, 129(7): e13-e25.
15. Yang J, Xiao X, Li R, et al. Hypermethylation of CpG sites at the promoter region is associated with deregulation of mitochondrial ATPsyn-β and chemoresistance in acute myeloid leukemia. Cancer Biomark, 2016, 16(1): 81-88.
16. 章红涛, 冯雅青, 赵芳, 等. 地西他滨联合半量 CAG 方案治疗复发难治急性髓系白血病效果观察. 白血病·淋巴瘤, 2018, 27(7): 404-406, 409.
17. 朱成英, 刘世研, 牛建花, 等. 地西他滨联合改良 CAG 方案治疗复发、难治型急性髓系白血病的临床研究. 中国实验血液学杂志, 2015, 23(1): 88-93.
18. 高然, 张蕊, 于锦香, 等. 地西他滨联合半量 CAG 方案治疗老年性及复发难治性急性髓细胞白血病的疗效分析. 中国医科大学学报, 2013, 42(6): 515-517.
19. 耿素红, 王微娜. 地西他滨联合改良 CAG 方案治疗复发、难治性急性髓系白血病的疗效观察. 中国医院用药评价与分析, 2018, 18(4): 509-510, 513.
20. Schroeder T, Rautenberg C, Haas R, et al. Hypomethylating agents for treatment and prevention of relapse after allogeneic blood stem cell transplantation. Int J Hematol, 2018, 107(2): 138-150.
21. Daver N, Kantarjian H, Ravandi F, et al. A phaseⅡ study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia, 2016, 30(2): 268-273.
22. Khan N, Hantel A, Knoebel RW, et al. Efficacy of single-agent decitabine in relapsed and refractory acute myeloid leukemia. Leuk Lymphoma, 2017, 58(9): 1-7.
23. 汪梅花, 赵康, 葛繁梅. 去甲基化药物联合 CAG 方案治疗老年白血病或难治复发性白血病疗效观察及对 VEGF、bFGF 的影响研究. 临床和实验医学杂志, 2018, 17(3): 311-314.
24. 杨柳, 葛健, 夏瑞祥. AML 对柔红霉素的耐药性与 TET2 基因突变的相关性. 安徽医科大学学报, 2018, 53(2): 242-246.
25. 姜艳红, 陈光意, 盛家和, 等. 外周血原始细胞比例高于骨髓的初治原发 AML 的临床特征及其与患者第一次完全缓解的关系. 实用医学杂志, 2018, 34(9): 1545-1549.
26. 苏龙, 李薇, 崔久巍, 等. 正常核型急性髓系白血病 NPM1、FLT3-ITD 突变与外周血白细胞数及骨髓原始细胞百分比相关性研究. 中国实验血液学杂志, 2013, 21(3): 571-575.

West China Medical Journal

Clinical therapeutic efficacy of decitabine contained chemotherapies on 101 patients with relapsed or refractory acute myeloid leukemia

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