阿糖胞苷联合伊马替尼治疗慢性粒细胞白血病的疗效观察
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摘要
目的探究阿糖胞苷联合伊马替尼治疗慢性粒细胞白血病的临床疗效。方法选取2014年2月—2017年1月石家庄市第一医院收治的慢性粒细胞白血病老年患者84例,随机分为对照组和治疗组,每组各42例。对照组患者口服甲磺酸伊马替尼片,400～600 mg/d,1次/d,根据病情可适当调整剂量。治疗组在对照组基础上静脉滴注注射用盐酸阿糖胞苷,20 mg/m2,6 h滴完,1次/d,每月持续输注10 d,若白细胞(WBC)<2.03109/L停止输注。两组患者连续治疗12个月。观察两组患者临床疗效,同时比较治疗前后两组患者骨髓细胞遗传学和血液学缓解率、外周血象变化、ABL1激酶突变率和预后情况。结果治疗后,治疗组患者主要骨髓细胞遗传学缓解率和完全血液学缓解率分别为35.70%、85.72%,均显著高于对照组患者的21.42%、64.28%,两组比较差异具有统计学意义(P<0.05)。治疗后,治疗组患者外周血幼稚细胞完全消失时间和血液学完全缓解时间均显著短于对照组,两组比较差异具有统计学意义(P<0.05)。治疗组患者ABL1基因突变率为21.42%,对照组患者突变率为35.71%,两组比较差异具有统计学意义(P<0.05)。随访12个月,治疗组患者原发耐药、复发和死亡发生率分别为7.14%、4.76%、0.00%,均显著低于对照组患者的21.42%、14.28%、9.52%,两组比较差异具有统计学意义(P<0.05)。结论阿糖胞苷联合伊马替尼治疗慢性粒细胞白血病老年患者能够有效提高骨髓细胞遗传学缓解率和完全血液学缓解率,降低ABL1激酶突变率,降低患者原发耐药、复发和死亡发生率,且不良反应低,具有一定的临床推广应用价值。
Objective To investigate the clinical efficacy of cytarabine combined with imatinib in treatment of chronic myeloid leukemia. Methods Patients(84 cases) with chronic myeloid leukemia in Shijiazhuang First Hospital from February 2014 to January2017 were randomly divided into control and treatment groups, and each group had 42 cases. Patients in the control group were po administered with Imatinib Mesylate Tablets, 400 — 600 mg/d, once daily, and adjusted the dosage appropriately according to the patient's condition. Patients in the treatment group were iv administered with Cytarabine Hydrochloride for injection on the basis of the control group, 20 mg/m2 for 6 h, once daily, monthly continuous infusion for 10 d, stopped infusion when WBC < 2.0× 109/L. Patients in two groups were treated for 12 months. After treatment, the clinical efficacy was evaluated, and the bone marrow cytogenetic remission rate and hematological remission rate, the changes of peripheral blood image, mutation rate of ABL1 kinase, prognosis in two groups before and after treatment were compared. Results After treatment, the bone marrow cytogenetic remission rate and hematological remission rate in the treatment group were 35.70% and 85.72%, which were significantly lower than 21.42% and 64.28% in the treatment group, respectively, and there were differences between two groups(P < 0.05). After treatment, the completely disappeared time of peripheral blood immature cells and the complete remission time of hematology in the treatment group was significantly lower than that in the control group, with significant difference between two groups(P < 0.05). After treatment, the mutation rate of ABL1 in the treatment group was 21.42%, which was significantly lower than 35.71% in the control group, with significant difference between two groups(P < 0.05). Follow-up for 12 months, the primary drug resistance, incidence of recurrence and death in the treatment group was 7.14%, 4.76%, and 0.00%, which was significantly lower than 21.42%, 14.28%, and 9.52% in the control group,respectively, and there were differences between two groups(P < 0.05). Conclusion Cytarabine combined with imatinib in treatment of chronic myeloid leukemia can effectively improve the bone marrow cytogenetic remission rate and hematological remission rate, reduce the mutation rate of ABL1 kinase, the primary drug resistance and incidence of recurrence and death, which has a certain clinical application value.
Objective To investigate the clinical efficacy of cytarabine combined with imatinib in treatment of chronic myeloid leukemia. Methods Patients(84 cases) with chronic myeloid leukemia in Shijiazhuang First Hospital from February 2014 to January2017 were randomly divided into control and treatment groups, and each group had 42 cases. Patients in the control group were po administered with Imatinib Mesylate Tablets, 400 — 600 mg/d, once daily, and adjusted the dosage appropriately according to the patient's condition. Patients in the treatment group were iv administered with Cytarabine Hydrochloride for injection on the basis of the control group, 20 mg/m2 for 6 h, once daily, monthly continuous infusion for 10 d, stopped infusion when WBC < 2.0× 109/L. Patients in two groups were treated for 12 months. After treatment, the clinical efficacy was evaluated, and the bone marrow cytogenetic remission rate and hematological remission rate, the changes of peripheral blood image, mutation rate of ABL1 kinase, prognosis in two groups before and after treatment were compared. Results After treatment, the bone marrow cytogenetic remission rate and hematological remission rate in the treatment group were 35.70% and 85.72%, which were significantly lower than 21.42% and 64.28% in the treatment group, respectively, and there were differences between two groups(P < 0.05). After treatment, the completely disappeared time of peripheral blood immature cells and the complete remission time of hematology in the treatment group was significantly lower than that in the control group, with significant difference between two groups(P < 0.05). After treatment, the mutation rate of ABL1 in the treatment group was 21.42%, which was significantly lower than 35.71% in the control group, with significant difference between two groups(P < 0.05). Follow-up for 12 months, the primary drug resistance, incidence of recurrence and death in the treatment group was 7.14%, 4.76%, and 0.00%, which was significantly lower than 21.42%, 14.28%, and 9.52% in the control group,respectively, and there were differences between two groups(P < 0.05). Conclusion Cytarabine combined with imatinib in treatment of chronic myeloid leukemia can effectively improve the bone marrow cytogenetic remission rate and hematological remission rate, reduce the mutation rate of ABL1 kinase, the primary drug resistance and incidence of recurrence and death, which has a certain clinical application value.
引文
[1]武英伟,张志华,张茉莉,等.复杂变异易位的慢性粒细胞白血病遗传学检查特点及预后分析[J].广东医学,2016,37(7):1021-1023.
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[8]徐卫,朱华渊,吴雨洁,等.慢性淋巴细胞白血病的诊断、预后与治疗[C].中华医学会第十一次全国血液学学术会议论文集.2010:90-111.
[9]陈莹.慢性粒细胞白血病与类白血病的临床病理学分析[J].医药前沿,2018,8(10):46-47.
[10]Breccia M,Alimena G.Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach[J].Expert Rev Hematol,2015,8(1):5-7.
[11]Shimoni A,Volchek Y,Koren-Michowitz M,et al.Phase 1/2study of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia[J].Cancer,2015,121(6):863-871.
[12]Celik S,Akcora D,Ozkan T,et al.Methylation analysis of the DAPK1 gene in imatinib-resistant chronic myeloid leukemia patients[J].Oncol Lett,2015,9(1):399-404.
[13]Ohm L,Lundqvist A,Dickman P,et al.Real-world cost-effectiveness in chronic myeloid leukemia:the price of success during four decades of development from non-targeted treatment to imatinib[J].Leuk Lymphoma,2015,56(5):1385-1391.
[14]黄林,石庆之.老年慢性粒细胞白血病慢性期患者酪氨酸激酶抑制剂治疗进展[J].中国老年学杂志,2016,36(17):4382-4384.
[15]范宗兄,石玉,刘日,等.第二代Bcr/Abl酪氨酸激酶抑制剂巴氟替尼[J].现代药物与临床,2012,27(3):268-271.
[16]余霞.CAG方案治疗老年急性髓细胞白血病的临床效果分析[C].2015临床急重症经验交流高峰论坛论文集.2015:714-715.
[2]杨丹,徐燕丽.不典型慢性粒细胞白血病诊断及治疗进展[J].白血病·淋巴瘤,2018,27(6):368-372.
[3]Radujkovic A,Guglielmi C,G Bergantini S,et al.Donor lymphocyte infusions for chronic myeloid leukemia relapsing after allogeneic stem cell transplantation:may we predict graft-versus-leukemia without graft-versushost disease[J].Biol Blood Marrow Transplant,2015,21(7):1230-1236.
[4]张琎,刘成林,赵平,等.伊马替尼治疗慢性粒细胞白血病的药物经济学定性系统评价[J].南昌大学学报:医学版,2017,57(5):29-32,61.
[5]Czader M,Orazi A.Acute myeloid leukemia and other types of disease progression in myeloproliferative neoplasms[J].Am J Clin Pathol,2015,144(2):188-206.
[6]刘宝文.慢性粒细胞白血病的诊断及治疗现状[C].中华中医药学会血液专业委员会第二届第六次血液学学术会议论文集.2006:43-50.
[7]丁慧芳.形态学、免疫学、细胞遗传学联合检测诊断急性白血病的临床意义[J].山东医药,2003,43(17):7-9.
[8]徐卫,朱华渊,吴雨洁,等.慢性淋巴细胞白血病的诊断、预后与治疗[C].中华医学会第十一次全国血液学学术会议论文集.2010:90-111.
[9]陈莹.慢性粒细胞白血病与类白血病的临床病理学分析[J].医药前沿,2018,8(10):46-47.
[10]Breccia M,Alimena G.Firstline treatment for chronic phase chronic myeloid leukemia patients should be based on a holistic approach[J].Expert Rev Hematol,2015,8(1):5-7.
[11]Shimoni A,Volchek Y,Koren-Michowitz M,et al.Phase 1/2study of nilotinib prophylaxis after allogeneic stem cell transplantation in patients with advanced chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia[J].Cancer,2015,121(6):863-871.
[12]Celik S,Akcora D,Ozkan T,et al.Methylation analysis of the DAPK1 gene in imatinib-resistant chronic myeloid leukemia patients[J].Oncol Lett,2015,9(1):399-404.
[13]Ohm L,Lundqvist A,Dickman P,et al.Real-world cost-effectiveness in chronic myeloid leukemia:the price of success during four decades of development from non-targeted treatment to imatinib[J].Leuk Lymphoma,2015,56(5):1385-1391.
[14]黄林,石庆之.老年慢性粒细胞白血病慢性期患者酪氨酸激酶抑制剂治疗进展[J].中国老年学杂志,2016,36(17):4382-4384.
[15]范宗兄,石玉,刘日,等.第二代Bcr/Abl酪氨酸激酶抑制剂巴氟替尼[J].现代药物与临床,2012,27(3):268-271.
[16]余霞.CAG方案治疗老年急性髓细胞白血病的临床效果分析[C].2015临床急重症经验交流高峰论坛论文集.2015:714-715.
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