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背景:异基因造血干细胞移植是目前公认的惟一可以治愈慢性粒细胞白血病的方法,但存在供体来源少,移植相关并发症较多等问题。甲磺酸伊马替尼作为近年来人工合成的基因产物靶向药物的代表,被越来越多地运用于Ph染色体阳性慢性粒细胞白血病患者的治疗中。目的:与亲缘异基因造血干细胞移植的历史资料对照,评价酪氨酸激酶抑制剂甲磺酸伊马替尼治疗慢性粒细胞白血病的有效性及安全性。设计、时间及地点:非随机化同系对照,于2002-04/2006-10在华中科技大学同济医学院附属协和医院血液病研究所完成。对象:选择华中科技大学同济医学院附属协和医院收治的慢性期慢性粒细胞白血病患者90例,所有患者在治疗前均经骨髓细胞学、细胞遗传学和/或分子遗传学检查确诊。方法:将90例慢性粒细胞白血病慢性期患者根据治疗方案分为两组。甲磺酸伊马替尼组67例,2002-04/2006-06陆续开始应用甲磺酸伊马替尼,观察截止时间为2006-10。口服甲磺酸伊马替尼400mg/d,每周复查血常规,每3个月进行骨髓象及细胞遗传学检查,根据血象和骨髓象调整剂量。亲缘异基因造血干细胞移植组23例,于1999-03/2006-04收治,均采用经典或改良白消安联合环磷酰胺方案预处理,短程甲氨蝶呤联合环孢素A方案预防移植物抗宿主病。主要观察指标:细胞遗传学反应以及两组患者的2年生存情况。结果:观察截止时,甲磺酸伊马替尼组患者的细胞遗传学完全缓解率显著低于亲缘异基因造血干细胞移植组(60%,100%,P<0.01)。亲缘异基因造血干细胞移植组和甲磺酸伊马替尼组患者的2年生存率分别为83.33%和77.03%,差异无显著性意义(P>0.05)。甲磺酸伊马替尼组治疗期间没有患者因药物副作用而停药、死亡,4例(5.97%)发生Ⅲ/Ⅳ级白细胞和/或血小板减少。亲缘异基因造血干细胞移植组中7例患者(30.4%)发生Ⅱ~Ⅳ度急性移植物抗宿主病,4例治疗无效死亡。结论:与亲缘异基因造血干细胞移植相比,甲磺酸伊马替尼治疗慢性粒细胞白血病患者2年生存率无差别,治疗相关并发症较少,但获得细胞遗传学完全缓解率较低。
BACKGROUND: Allogeneic hematopoietic stem cell transplantation is the only accepted method that can cure chronic myeloid leukemia. However, there are many problems such as fewer donor sources and more graft-related complications. Imatinib mesylate, as a representative of targeted synthetic drugs in recent years, has been increasingly used in the treatment of patients with Ph chromosome-positive chronic myeloid leukemia. OBJECTIVE: To evaluate the efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate in the treatment of chronic myelogenous leukemia in comparison with historical data of allogeneic hematopoietic stem cell transplantation. DESIGN, TIME AND SETTING: A nonrandomized homologous control was performed at the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from April 2002 to October 2006. PARTICIPANTS: Ninety patients with chronic myeloid leukemia who were treated at Tongji Medical College Affiliated Union Hospital of Huazhong University of Science and Technology were selected. All patients were confirmed by myelocytology, cytogenetics and / or molecular genetics before treatment. Methods: Ninety chronic patients with chronic myeloid leukemia were divided into two groups according to the treatment plan. 67 cases of imatinib mesylate group, imatinib mesylate since 2002-04 / 2006-06 began to apply, the observation deadline for the 2006-10. Oral imatinib mesylate 400mg / d, weekly review of blood routine, bone marrow biopsy and cytogenetic examination every 3 months, according to blood and bone marrow like dose adjustment. Allogeneic hematopoietic stem cell transplantation group, 23 cases, were treated from 1999-03 / 2006-04, were treated with classic or modified busulfan plus cyclophosphamide pretreatment, short-course methotrexate combined with cyclosporin A to prevent graft Anti-host disease. MAIN OUTCOME MEASURES: Cytogenetic response and 2-year survival in both groups. Results: At the end of the study, cytogenetic complete remission rates in the imatinib mesylate group were significantly lower than those in the allogeneic hematopoietic stem cell transplantation group (60%, 100%, P <0.01). The 2-year survival rates of allogeneic hematopoietic stem cell transplantation and imatinib mesylate groups were 83.33% and 77.03%, respectively, with no significant difference (P> 0.05). None of the patients in the imatinib mesylate group were discontinued due to drug side effects during the treatment period, and 4 (5.97%) patients had stage III / IV leukocytes and / or thrombocytopenia. Seven patients (30.4%) in the allogeneic allogeneic hematopoietic stem cell transplantation group had grade Ⅱ ~ Ⅳ acute graft-versus-host disease, and 4 cases died of treatment ineffectiveness. CONCLUSION: Compared with kinship allogeneic hematopoietic stem cell transplantation, the 2-year survival rate of patients with chronic myeloid leukemia treated with imatinib mesylate is indistinctive, and there are fewer treatment-related complications. However, the complete cytogenetic remission rate is lower.