地西他滨联合低剂量阿糖胞苷治疗老年复发/难治性急性髓系白血病患者的疗效、预后及安全性分析
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摘要
目的:探讨地西他滨联合低剂量CAG化疗方案治疗老年复发/难治性急性髓系白血病(acute myeloid leukemia,AML)患者的疗效、预后及安全性。方法:回顾性分析本院在2014年1月至2016年8月收治的40例老年复发/难治性AML患者(69-85岁)的临床资料,根据治疗方案不同分为联合治疗组和对照组,各20例。联合治疗组采用地西他滨联合低剂量CAG方案(地西他滨,15 mg/m~2,d 1;阿克拉霉素,10 mg/m~2,d 3-6;注射用阿糖胞苷,10 mg/m~2,d 1-14;注射用重组人粒细胞巨噬细胞集落刺激因子(G-CSF),200μg/(m~2·d),d 1-14)。对照组采用标准CAG方案(阿克拉霉素20 mg/m~2,d 1-4;注射用阿糖胞苷,15 mg/m~2,d 1-14;G-CSF400μg/(m~2·d),d 1-14)。2周1疗程,连续用药2个疗程。比较2组患者的完全缓解率(CR)、总缓解率(ORR),总生存时间(overall survival,OS)、1年生存率,血红蛋白、白细胞、血小板的改善,不良反应发生率。结果:联合治疗组CR 55.00%(11/20),OR 85.00%(17/20)(P <0.05);CAG组CR 30.00%(6/20),OR50.00%(10/20)。截止至2018年2月,40例患者中17例存活,20例死亡,3例失访,中位随访时间12(2-35)个月。联合治疗组中位生存时间13(2-35)个月,1年OS率为70.00%;CAG组中位生存时间10(2-31)个月,1年OS率为50.00%,差异无统计学意义(P> 0.05)。治疗后联合治疗组外周血WBC、Plt数高于CAG组,Hb水平低于CAG组,差异具有统计学意义(P<0.05)。联合治疗组肺部感染、恶心呕吐发生率高于CAG组(65.00%vs 25.00%,50.00%vs 20.00%),差异具有统计学意义(P <0.05)。结论:地西他滨联合低剂量CAG方案治疗老年复发/难治性AML近期疗效显著,远期疗效并无差异,但不良反应增加,在临床在治疗过程中要及时给予预防性处理。
Objective: To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 40 elderly patients with relapsed/refractory AML(69-85 years old) admitted to our hospital from January 2014 to August2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG(decitabine, 15 mg/m~2, d 1; aclarithromycin, 10 mg/m~2, d 3-6; Cytidine, 10 mg/m~2, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor(G-CSF) for injection, 200 μg/(m~2·d), d 1-14).20 patients of CAG group were treated by the standard CAG protocol(acralmycin 20 mg/m~2, d 1-4; cytarabine for injection, 15 mg/m~2, d 1-14; G-CSF 400 μg/(m~2·d), d 1-14). One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate(CR), overall remission rate(ORR), overall survival(OS), 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared. Results: In combination therapy group the CR was 55.00%(11/20), OR was 85.00%(17/20), but in the CAG group CR was 30.00%(6/20), and OR was 50.00%(10/20). Till to February 2018, out of 40 patients17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12(2 to 35) months; the median survival time in the comtination therapy group was 13(2-35) months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10(2-31) months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups(P >0.05). After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference(P <0.05). In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group(65.00% vs 25.00%, 50.00% vs 20.00%), with statistically significant difference(P <0.05). Conclusion: Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.
Objective: To investigate the efficacy, prognosis and safety of decitabine combined with low-dose CAG regimen in the treatment of elderly patients with acute myeloid leukemia(AML). Methods: The clinical data of 40 elderly patients with relapsed/refractory AML(69-85 years old) admitted to our hospital from January 2014 to August2016 were analyzed retrospectively. 40 patients were divided into combination therapy group and CAG group according to different treatment methods. 20 patients of the combination therepy group were treated with decitabine combined with low-dose CAG(decitabine, 15 mg/m~2, d 1; aclarithromycin, 10 mg/m~2, d 3-6; Cytidine, 10 mg/m~2, d 1-14; recombinant human granulocyte macrophage colony-stimulating factor(G-CSF) for injection, 200 μg/(m~2·d), d 1-14).20 patients of CAG group were treated by the standard CAG protocol(acralmycin 20 mg/m~2, d 1-4; cytarabine for injection, 15 mg/m~2, d 1-14; G-CSF 400 μg/(m~2·d), d 1-14). One course of treatment lasted for 2 weeks, after 2 courses of continuous medication, the complete remission rate(CR), overall remission rate(ORR), overall survival(OS), 1-year survival rate, hemoglobin, white blood cells, platelets improvement, and incidence of adverse reactions were compared. Results: In combination therapy group the CR was 55.00%(11/20), OR was 85.00%(17/20), but in the CAG group CR was 30.00%(6/20), and OR was 50.00%(10/20). Till to February 2018, out of 40 patients17 survived, 20 died, and 3 failed to be followed-up. The median follow-up time was 12(2 to 35) months; the median survival time in the comtination therapy group was 13(2-35) months, and the 1-year OS rate was 70.00%, and the median survival time of the CAG group was 10(2-31) months, and the 1-year OS rate was 50.00%, without staistical significance between the 2 groups(P >0.05). After treatment, the WBC and Plt counts in the combination therapy group were higher than those in the CAG group, but the Hb level was lower than that in the CAG group with statistically significant difference(P <0.05). In the combination therapy group, the incidence of lung infection, nausea and vomiting was higher than that of the CAG group(65.00% vs 25.00%, 50.00% vs 20.00%), with statistically significant difference(P <0.05). Conclusion: Decitabine combined with low-dose CAG regimen is effective for the treatment of relapsed/refractory AML in the elderly. Compared with the standard CAG regimen, the long-term efficacy of this regimen is not different significantly, but its adverse reactions are increase, thus the preventive treatment should be given in time.
引文
1刘晓,秦兰,李巍,等. CAG方案联合地西他滨治疗老年急性髓系白血病40例应用分析.肿瘤学杂志, 2017; 23(2):150-153.
2 周宏伟,周敏航,王志红,等.地西他滨单药或联合以阿糖胞苷为基础的低剂量化疗方案治疗老年急性髓系白血病的临床分析.中国实验血液学杂志, 2018; 26(1):91-96.
3 Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia.N Engl J Med, 2015; 373(12):1136-1152.
4 Hassan C, Afshinnekoo E, Li S, et al. Genetic and epigenetic heterogeneity and the impact on cancer relapse. Exp Hematol, 2017;54:26-30.
5 张之南,沈悌.血液病诊断及疗效标准.第3版.北京:科学出版社, 2007; 106-116.
6 Stahl M, Lu BY, Kim TK, et al. Novel therapies for acute myeloid leukemia:are we finally breaking the deadlock? Target Oncol,2017; 12(4):413-447.
7 O'Donnell MR, Tallman MS, Abboud CN, et al. Acute myeloid leukemia, version 3. 2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2017; 15(7):926-957.
8 赵彩芳,胡慧仙,骆超,等。地西他滨联合CAG方案治疗MDS-RAEB及难治性急性髓系白血病的疗效与安全性观察.药物流行病学杂志, 2016; 25(7):422-425.
9 陆惠娜,丁-懿,修冰,等.地西他滨联合CAG方案治疗老年急性髓系白血病疗效观察.同济大学学报(医学版), 2 016;37(3):71-75.
10 蔡艳青.地西他滨联合CAG方案治疗老年急性髓系白血病临床疗效观察.山东医药, 2016; 56(5):90-91.
11 Chen C, Xu W, Yang J. Low-dose homohar ringtonine and cytarabine in combination with granulocyte colony-stimulating factor for elderly patients with de novo acute myeloid leukemia.Leuk Lymphoma, 2015; 56(1):141-146.
12 Heiblig M, Elhamri M, Tigaud I, et al. Treatment with low-dose cytarabine in elderly patients(age 70 years or older)with acute myeloid leukemia:a single institution experience. Mediterr J Hematol Infect Dis, 2016; 8(1):e2016009.
13 Taylor J, Xiao W, Abdel-Wahab O. Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood, 2017;130(4):410-423.
14 康思静,王婷婷,高然,等.地西他滨联合小剂量CAG治疗老年急性髓系白血病疗效研究.中国实用内科杂志, 2016; 36(5):406-407.
15 刘强,费小明.地西他滨联合CAG方案治疗AML1-ETO+AML的临床效果.中国实验血液学杂志, 2016; 24(5):1334-1338.
16 Li J,Chen Y,Zhu Y,et al. Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia.Oncotarget. 2015; 6(8):6448-6458.
17 Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults:2017 ELN recommendations from an international expert panel. Blood, 2017; 129(4):424-447.
18 张红霞,吴广胜,王燕.,等.地西他滨联合半量CAG方案治疗老年急性髓系白血病的临床疗效.中国老年学杂志,2016; 10(20):5058-5060.
19 Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med, 2016; 374(23):2209-2221.
20 Zhu CY, Liu SY, Niu JH, et al. Clinical research of decitabine combined with modified CAG regimen for treatment of relapsed or refractory acute myeloid leukemia.中国实验血液学杂志, 2015;23(1):88-93.
21 陈丽,郝云良.地西他滨联合CAG方案治疗老年急性髓系白血病的疗效观察.临床血液学杂志, 2015; 28(3):233-236.
2 周宏伟,周敏航,王志红,等.地西他滨单药或联合以阿糖胞苷为基础的低剂量化疗方案治疗老年急性髓系白血病的临床分析.中国实验血液学杂志, 2018; 26(1):91-96.
3 Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia.N Engl J Med, 2015; 373(12):1136-1152.
4 Hassan C, Afshinnekoo E, Li S, et al. Genetic and epigenetic heterogeneity and the impact on cancer relapse. Exp Hematol, 2017;54:26-30.
5 张之南,沈悌.血液病诊断及疗效标准.第3版.北京:科学出版社, 2007; 106-116.
6 Stahl M, Lu BY, Kim TK, et al. Novel therapies for acute myeloid leukemia:are we finally breaking the deadlock? Target Oncol,2017; 12(4):413-447.
7 O'Donnell MR, Tallman MS, Abboud CN, et al. Acute myeloid leukemia, version 3. 2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw, 2017; 15(7):926-957.
8 赵彩芳,胡慧仙,骆超,等。地西他滨联合CAG方案治疗MDS-RAEB及难治性急性髓系白血病的疗效与安全性观察.药物流行病学杂志, 2016; 25(7):422-425.
9 陆惠娜,丁-懿,修冰,等.地西他滨联合CAG方案治疗老年急性髓系白血病疗效观察.同济大学学报(医学版), 2 016;37(3):71-75.
10 蔡艳青.地西他滨联合CAG方案治疗老年急性髓系白血病临床疗效观察.山东医药, 2016; 56(5):90-91.
11 Chen C, Xu W, Yang J. Low-dose homohar ringtonine and cytarabine in combination with granulocyte colony-stimulating factor for elderly patients with de novo acute myeloid leukemia.Leuk Lymphoma, 2015; 56(1):141-146.
12 Heiblig M, Elhamri M, Tigaud I, et al. Treatment with low-dose cytarabine in elderly patients(age 70 years or older)with acute myeloid leukemia:a single institution experience. Mediterr J Hematol Infect Dis, 2016; 8(1):e2016009.
13 Taylor J, Xiao W, Abdel-Wahab O. Diagnosis and classification of hematologic malignancies on the basis of genetics. Blood, 2017;130(4):410-423.
14 康思静,王婷婷,高然,等.地西他滨联合小剂量CAG治疗老年急性髓系白血病疗效研究.中国实用内科杂志, 2016; 36(5):406-407.
15 刘强,费小明.地西他滨联合CAG方案治疗AML1-ETO+AML的临床效果.中国实验血液学杂志, 2016; 24(5):1334-1338.
16 Li J,Chen Y,Zhu Y,et al. Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia.Oncotarget. 2015; 6(8):6448-6458.
17 Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults:2017 ELN recommendations from an international expert panel. Blood, 2017; 129(4):424-447.
18 张红霞,吴广胜,王燕.,等.地西他滨联合半量CAG方案治疗老年急性髓系白血病的临床疗效.中国老年学杂志,2016; 10(20):5058-5060.
19 Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med, 2016; 374(23):2209-2221.
20 Zhu CY, Liu SY, Niu JH, et al. Clinical research of decitabine combined with modified CAG regimen for treatment of relapsed or refractory acute myeloid leukemia.中国实验血液学杂志, 2015;23(1):88-93.
21 陈丽,郝云良.地西他滨联合CAG方案治疗老年急性髓系白血病的疗效观察.临床血液学杂志, 2015; 28(3):233-236.