国产甲磺酸伊马替尼治疗初诊慢性髓系白血病慢性期的临床研究

Clinical study of domestic imatinib mesylate in the treatment of newly diagnosed chronic myeloid in chronic phase

目的:评价国产甲磺酸伊马替尼治疗初诊慢性髓系白血病慢性期(CML-CP)的疗效和安全性。方法:94例初诊的CML-CP患者接受口服国产甲磺酸伊马替尼治疗,400mg/次,每日1次,评价治疗3、6、12个月时的血液学、细胞遗传学和分子学反应以及安全性。结果:94例CML-CP患者均治疗≥3个月,其中治疗≥6个月者87例,治疗≥12个月者78例。治疗满3个月时,88例(93.6%)获得完全血液学反应(CHR)。51例患者进行了细胞遗传学检查,18例(35.3%)获得主要细胞遗传学反应(MCyR),其中7例(13.7%)获得完全细胞遗传学反应(CCyR)。94例患者均进行BCR-ABL融合基因转录本水平检测,其中BCR-ABL≤10%的患者有68例(72.3%),达到主要分子学反应(MMR:BCR-ABL≤0.1%)的患者有9例(9.6%)。治疗满6个月时,85例(97.7%)获得CHR。48例患者进行了细胞遗传学检查,34例(70.8%)获得MCyR,其中17例(35.4%)获得CCyR。87例患者均进行BCR-ABL融合基因转录本水平检测,BCR-ABL≤1%的患者有44例(50.6%),达到MMR的患者15例(17.2%)。治疗满12个月时,所有患者(100%)获得CHR。60例患者进行了细胞遗传学检查,49例(81.7%)获得MCyR,其中41例(68.3%)获得CCyR。78例患者进行BCR-ABL融合基因转录本水平检测,达到MMR的患者22例(28.2%)。Ⅲ级白细胞减少、血小板减少以及贫血的发生率分别为8.5%、2.1%、4.3%,无Ⅳ级血液学不良反应发生。非血液学不良反应依次为恶心(51.1%)、呕吐(30.9%)、疲劳(7.4%)、皮疹(23.4%)、发热(12.8%)、头痛(14.9%)、腹泻腹痛(37.2%)、周围浮肿(51.1%)、肝功能异常(6.4%),多为Ⅰ～Ⅱ级,Ⅲ级非血液学不良反应极少见,仅5例(5.3%)患者发生Ⅲ级皮疹,无一例患者出现Ⅳ级非血液学不良反应。结论:国产甲磺酸伊马替尼治疗初诊CML-CP的早期疗效肯定,安全性良好。

Objective:To evaluate the early clinical efficacy and safety in newly diagnosed patients with chronic myelogenous leukemia in chronic phase(CML-CP)and initially treated with domestic imatinib mesylate.Method:A total of 94 newly diagnosed patients of CML-CP were treated with domestic imatinib mesylate 400 mg/qd po.The hematologic,cytogenetic and molecular responses were assessed at 3,6 and 12 month and adverse events were evaluated.Result:The 94 patients were treated with domestic imatinib mesylate≥3 months,87 of them were treated≥6 months and 78 of them were treated≥12 months.At the 3 rd month,the complete hematologic responses(CHR)rate was 93.6%,meanwhile 18/51(35.3%)patients had major cytogenetic response(MCyR)and 7/51(13.7%)patients had complete cytogenetic response(CCyR);BCR-ABLIS was≤10%in 68/94 patients(72.3%),moreover,9 of them(9.6%)had major molecular response(MMR:BCR-ABLIS was≤0.1%).At the 6 th month,the CHR rate was 97.7%(85/87);34/48 patients(70.8%)had MCyR;17/48 patients(35.4%)had CCyR;BCRABLIS was≤1%in 44/87 patients(50.6%),and 15 of them(17.2%)had MMR.At the 12 th month,the CHR rate was 100%(94/94);49/60 patients(81.7%)had MCyR;41/60 patients(68.3%)had CCyR;22/78 patients(28.2%)had MMR.The adverse event rate in grade Ⅲ with leucopenia,thrombocytopenia and anemia was 8.5%,2.1% and 4.3%,respectively.There was no hematology adverse events in grade Ⅳ.The non-hematologic adverse events were nausea(51.1%),emesis(30.9%),fatigue(7.4%),rash(23.4%),fever(12.8%),headache(14.9%),abdominal pain of diarrhoea(37.2%),peripheral edema(51.1%),and impaired liver function(6.4%),mostly gradeⅠ-Ⅱ.Grade Ⅲ non-hematological adverse events were rare,only 5 cases(5.3%)had gradeⅢrash.No patient experienced gradeⅣ non-hematologic adverse events.Conclusion:The study reveals the excellent early clinical efficacy and safety in CML-CP treated with domestic imatinib mesylate in the early stage.