国产甲磺酸伊马替尼治疗初诊慢性粒细胞白血病慢性期临床观察

Single-center clinical trial of 43 cases patients with chronic phase of chronic myelogenous leukemia treated with generic imatinib

目的甲磺酸伊马替尼作为治疗慢性粒细胞白血病(chronic myelogenous leukemia,CML)-慢性期(chronic phase,CP)患者的一线治疗药物,国产药物应用的安全性和有效性尚缺乏系统评价参考。本研究探讨国产甲磺酸伊马替尼治疗初诊CML-CP患者的早期血液学、细胞遗传学、分子学反应与安全性。方法收集2014-03-01-2015-10-31就诊于新疆自治区人民医院血液科的43例初诊CML-CP患者,给予国产甲磺酸伊马替尼(昕维○R)400mg/d口服,治疗3、6、12个月时进行骨髓细胞学、染色体、FISH与骨髓BCR-ABL融合基因转录本水平评估,观察评估患者血液学反应、细胞遗传学反应和分子学反应及安全性。结果 43例患者治疗满3个月时,42例(97.7%)达完全血液学反应(complete hematologic response,CHR);35例(81.4%)达主要细胞遗传学反应(major cytogenetic response,MCyR),其中11例(25.6%)达完全细胞遗传学反应(complete cytogenetic response,CCyR);30例(69.8%)达国际标准化BCR-ABL转录本水平(BCR-ABL^(IS))≤10%,4例(9.3%)达BCR-ABLIS≤0.1%。17例患者治疗满6个月时,均达CHR(100.0%);11例(64.7%)达CCyR;12例(70.6%)达BCR-ABLIS≤1%,其中4例(23.5%)达BCR-ABLIS≤0.1%。5例患者治疗满12个月,4例达CCyR;2例BCR-ABLIS≤1%,2例BCR-ABLIS≤0.1%,1例BCR-ABLIS>10%。血液学不良反应:3/4级白细胞减少、血小板减少和贫血发生率分别为20.9%、23.3%和16.3%。非血液学不良反应发生率分别为水肿76.7%,恶心呕吐51.2%,骨关节肌肉酸痛39.5%),皮疹20.9%,发热11.6%,腹泻11.6%,肝功能损害2.3%。无4/4级血液学与非血液学不良反应。结论国产甲磺酸伊马替尼治疗初诊CML-CP患者的近期疗效肯定,不良反应可耐受,但仍需长期观察研究。

OBJECTIVE Imatinib is the first-line agent in patients with chronic phase of chronic myelogenous leuke- mia in chronic phase（CML-CP）, however, the safety and efficacy of generic imatinib is still not clear. This study was to e- valuate the early hematologic, cytogenetic, molecular response and safety in newly diagnosed patients with CML-CP and initially treated with a generic imatinib （Xinwei）. METHODS Totally 43 newly diagnosed patients of CML-CP,were se- lected from the Department of Hematology, the Xinjiang Uygur Autonomous Region people, s Hospital from March 1, 2014 to October 31,2015 ,who had never received any tyrosine kinase inhibitor （TKI） and they were treated with Xinwei 400 mg PO. The hematologic,cytogenetic and molecular responses were assessed at 3,6 and 12 month, and the adverse effects were evaluated throughout the study. RESULTS Totally 43 patients were treated with Xinwei for 3 months,the complete hematologic responses （CHR） rate were 97.7% （42/43） ; 81.4%（35/43） patients achieved major cytogenetic re- sponse （MCyR）. 68 % （11/43） patients had complete cytogenetic response （CCyR） ;BCR-ABLIS was 410 % in 69.8 % patients （30/43）, 4 of them （9.3 % ） achieved major molecular response（MMR, BCR-ABLIS was ≤0.1% ）. At 6 month, the complete hematologic responses （CHR） rate were 100.0% （17/17） ; 64. 7% （11/17） patients had complete cytogeneticresponse （CCyR） ; BCR-ABLIs was 41% in 70.6% patients （12/17）,and 4 of them （23.5%） achieved major molecular response （MMR,BCR-ABLis was 40.1%）. Five patients were treated with Xinwei for 12 months,4 of them had com- plete cytogenetic response （CCyR） ; BCR-ABLIS was ≤ 1% in 2 patients, BCR-ABLIS was ≤0.1% in 2 patients, and BCR- ABLIS was ≤10% in 1 patients. The grade N- IV leukopenia,thrombocytopenia and anemia rates were 20.9% ,23.3% and 16.3 %, respectively. No grade IV--IV hematologic toxicity occurred. The common non-hematologic toxicities were e- dema （76.7%）,nausea （51.2%）,bone pain （39.5%） ,rash （20.9%） ,diarrhea （11.6%） ,fever （11.6%） and impaired liver function （2.3 %）. CONCLUSION The excellent early haematology,cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP,but it still needs a long term study.