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.	中華醫學會血液學分會, 中國醫師協會血液科醫師分會. 中國中性粒細胞缺乏伴發熱患者抗菌藥物臨床應用指南(2016 年版). 中華血液學雜志, 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.	王利軍, 丁潔, 朱成英, 等. FLAG 方案治療難治復發急性髓系白血病的臨床研究. 中國實驗血液學雜志, 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.	章紅濤, 馮雅青, 趙芳, 等. 地西他濱聯合半量 CAG 方案治療復發難治急性髓系白血病效果觀察. 白血病·淋巴瘤, 2018, 27(7): 404-406, 409.
17.	朱成英, 劉世研, 牛建花, 等. 地西他濱聯合改良 CAG 方案治療復發、難治型急性髓系白血病的臨床研究. 中國實驗血液學雜志, 2015, 23(1): 88-93.
18.	高然, 張蕊, 于錦香, 等. 地西他濱聯合半量 CAG 方案治療老年性及復發難治性急性髓細胞白血病的療效分析. 中國醫科大學學報, 2013, 42(6): 515-517.
19.	耿素紅, 王微娜. 地西他濱聯合改良 CAG 方案治療復發、難治性急性髓系白血病的療效觀察. 中國醫院用藥評價與分析, 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, 趙康, 葛繁梅. 去甲基化藥物聯合 CAG 方案治療老年白血病或難治復發性白血病療效觀察及對 VEGF、bFGF 的影響研究. 臨床和實驗醫學雜志, 2018, 17(3): 311-314.
24.	楊柳, 葛健, 夏瑞祥. AML 對柔紅霉素的耐藥性與 TET2 基因突變的相關性. 安徽醫科大學學報, 2018, 53(2): 242-246.
25.	姜艷紅, 陳光意, 盛家和, 等. 外周血原始細胞比例高于骨髓的初治原發 AML 的臨床特征及其與患者第一次完全緩解的關系. 實用醫學雜志, 2018, 34(9): 1545-1549.
26.	蘇龍, 李薇, 崔久巍, 等. 正常核型急性髓系白血病 NPM1、FLT3-ITD 突變與外周血白細胞數及骨髓原始細胞百分比相關性研究. 中國實驗血液學雜志, 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. 中華醫學會血液學分會, 中國醫師協會血液科醫師分會. 中國中性粒細胞缺乏伴發熱患者抗菌藥物臨床應用指南(2016 年版). 中華血液學雜志, 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. 王利軍, 丁潔, 朱成英, 等. FLAG 方案治療難治復發急性髓系白血病的臨床研究. 中國實驗血液學雜志, 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. 章紅濤, 馮雅青, 趙芳, 等. 地西他濱聯合半量 CAG 方案治療復發難治急性髓系白血病效果觀察. 白血病·淋巴瘤, 2018, 27(7): 404-406, 409.
17. 朱成英, 劉世研, 牛建花, 等. 地西他濱聯合改良 CAG 方案治療復發、難治型急性髓系白血病的臨床研究. 中國實驗血液學雜志, 2015, 23(1): 88-93.
18. 高然, 張蕊, 于錦香, 等. 地西他濱聯合半量 CAG 方案治療老年性及復發難治性急性髓細胞白血病的療效分析. 中國醫科大學學報, 2013, 42(6): 515-517.
19. 耿素紅, 王微娜. 地西他濱聯合改良 CAG 方案治療復發、難治性急性髓系白血病的療效觀察. 中國醫院用藥評價與分析, 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, 趙康, 葛繁梅. 去甲基化藥物聯合 CAG 方案治療老年白血病或難治復發性白血病療效觀察及對 VEGF、bFGF 的影響研究. 臨床和實驗醫學雜志, 2018, 17(3): 311-314.
24. 楊柳, 葛健, 夏瑞祥. AML 對柔紅霉素的耐藥性與 TET2 基因突變的相關性. 安徽醫科大學學報, 2018, 53(2): 242-246.
25. 姜艷紅, 陳光意, 盛家和, 等. 外周血原始細胞比例高于骨髓的初治原發 AML 的臨床特征及其與患者第一次完全緩解的關系. 實用醫學雜志, 2018, 34(9): 1545-1549.
26. 蘇龍, 李薇, 崔久巍, 等. 正常核型急性髓系白血病 NPM1、FLT3-ITD 突變與外周血白細胞數及骨髓原始細胞百分比相關性研究. 中國實驗血液學雜志, 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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