甲磺酸伊马替尼与亲缘异基因造血干细胞移植治疗慢性期慢性粒细胞白血病的有效性及安全性差异

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绎骨髓细胞学、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200610。口服甲磺酸伊马替尼400mg／d，每剧复查血常规，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于奂处理，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（JP〉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。亲缘异基因造血十细胞移植组中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。

Efficacy and safety comparison between imatinib mesylate and allogenic hematopoietic stem cell transplantation for treating chronic myelogenous leukemia

BACKGROUND: Allogeneic hematopoietic stem cell transplantation is recognized as the only method of curing chronic myelocytic leukemia (CML). Lmatinib mesylate (STI571) is a competitive inhibitor of the bcr-abl tyrosine kinase, as a represent of synthetic gene-targeting drug in recently, which has been used more and more on the Philadelphia chromosome positive CML patients.OBJECTIVE: To compare the efficacy and safety of STI571 to related allogenic hematopoietic stem cell transplantation in the treatment of CML patients.DESIGN, TIME AND SETTING: A controlled observation between ST1571 treated group and transplantation group was performed in the Department of Hematology, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology between April 2002 and October 2006. PARTICIPANTS: All 90 patients with CML in the chronic phase were selected from Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, and they were diagnosis based on the examinations of bone marrow morphologic, cytogenetics and/or molecular genetics. METHODS: All 90 patients with CML in the chronic phase were divided into two groups. 67 patients received oral STI571 (400 mg/day) in succession at the beginning time from April 2002 to June 2006, and the observation ended until October 2006, Blood routine will be done weekly, and bone marrow morphologic and cytogenetic examination would be done every three months. Other 23 patients selected from Union Hospital from March 1999 to April 2006 accepted allo-HSCT, with BuCy2 or modified BuCy2 as conditioning regimens. Cyclosporin A combining with short-term MTX were used in all patients for prophylaxis of graft-versus-host disease (GVHD). MAIN OUTCOME MEASURES: Hematology responses, eytogenetic response and two years survival in two groups were observed. RESULTS: Complete cytogenetic response was achieved in 60% and 100% of the patient treated with STI571 and transplantation respectively (P < 0.01). But two years survival of ST1571 and transplantation were 83.33% and 77.03% respectively, and no difference was found between the two groups (P > 0.05). No one died or discontinued therapy for adverse effects, and 4 out of 67 (5.97%) had grade 3 or 4 thrombocytopenia and/or leucopenia in the ST1571 group. Moreover, in transplantation group, 7 patients (30.4%) developed grade 2 to 4 acute GVHD, but 4 died of failed treatment. CONCLUTION: Compared with transplantation, patients treated with ST1571 achieved low complete cytogenetic responses and the treatment-related complications were mild and manageable or no need for treatment.