GHA及新型联合预激化疗方案治疗难治性急性髓系白血病和骨髓增生异常综合征的队列研究  

Cohort Study on GHA and New Combined Priming Chemotherapeutic Regimens in Treatment of Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

作　　者：马肖容[1] 王瑾[1] 张王刚[1] 陈银霞[1] 曹星梅[1] 何爱丽[1] 刘捷[1] 王剑利[1] 古流芳[1] 雷博[1] 张鹏宇[1] 赵万红[1] 杨云[1] 王芳侠[1] 徐燕[1] 

机构地区：[1]西安交通大学第二附属医院血液内科,陕西西安710004

出　　处：《中国实验血液学杂志》2015年第2期369-374,共6页Journal of Experimental Hematology

基　　金：2013年陕西省科学技术研究发展计划项目(2013K12-06-03)

摘　　要：目的:本文探讨GHA(G-CSF+高三尖杉酯碱+小剂量阿糖胞苷)及GHAA和GHTA等新型联合预激化疗方案治疗难治性急性髓系白血病(AML)和骨髓增生异常综合征(MDS)的临床疗效和不良反应,寻求高效低毒的新型化疗方案,并探索其与共刺激分子B7.1的关系。方法:应用GHA标准预激化疗方案,即G-CSF 100μg/(m2·d)皮下注射,d 0-14;高三尖杉酯碱1.0 mg/(m2·d)静脉点滴,d 1-14;阿糖胞苷(Ara-C)7.5-10 mg/(m2·d)皮下注射,q12h,d 1-14,以及GHAA、GHTA等联合预激化疗(联合阿柔比星20 mg d 1-7或吡柔比星20 mg d 1-7)治疗74例难治性急性髓系白血病和46例骨髓增生异常综合征(RAEB和RAEBT),与常规化疗组(MA、TAE方案)56例比较,分别观察不同方案的临床疗效,不良反应,治疗相关死亡率并随访生存;同时应用免疫荧光法检测各组肿瘤细胞上共刺激分子B7.1的表达并与临床疗效比较。结果:1预激化疗组治疗难治性AML缓解率67.56%(CR率54.05%,PR率13.51%),疗效显著优于常规化疗组(P<0.05),其中AML-M2组、AML-M5组CR率(65.51%,61.90%)显著高于其它AML亚型(P<0.05),最长持续缓解已4年,2治疗MDS缓解率60.87%(CR率45.65%,PR率15.22%),预激化疗组疗效也显著优于常规化疗组(P<0.05)。3与GHA标准预激化疗相比,无论难治性AML还是MDS,新型联合预激化疗缓解率较高,其中AML缓解率为85.18%,MDS缓解率为81.25%,均有显著性差异(P<0.05)。4化疗后出现粒细胞缺乏及血小板减少、贫血等,平均持续时间7-14 d,重症感染发生率1%,无严重出血、消化道反应和心、肝、肾功能损害,治疗相关死亡率为零。预激化疗组主要观察指标与常规化疗组相比,Ⅲ/Ⅳ毒副作用明显减轻,安全性好,具有统计学差异(P<0.05)。5AML和MDS以及不同类型B7.1表达阳性率差异较大,AML-M2组、AML-M5组明显高于其它AML组(P<0.05)。同一病例B7.1表达与预激化疗疗效呈正相关,即化疗有效病例B7.1表达往往阳性,而B7.1表达阴性者的�Objective： To explore the clinical efficacy and adverse effects of GHA（ G-CSF ＋ homoharringtonin ＋ cytarabine C） and new combined priming chemotherapeutic regimens（GHAA/GHTA） with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia（AML） and myelodysplastic syndrome（ MDS）, and toanalyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7. 1. Methods： Standard GHA regimen consisting of G-CSF： 100 μg/（ m2· d） subcutaneous injection, d 0 - 14; homoharringtonine： 1.0 mg/（m2 · d） intravenous drip, d 1 - 14 ; Ara-C： 7.5 - 10 mg/（m2 · d） subcutaneous injection, ql2h, d 1 - 14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1 - 7, or pirarubicin 20 mg d 1 - 7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy （MA/TAE） respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored. Results： （1） for AML patients treated with priming chemotherapy, the total remission was 67.56% （CR 54.05%, PR 13.51% ）, which was much higher than that of patients received routine chemotherapy （ P 〈 0.05 ）. The CR rate of AML-M2 and AML-M5 group （65.51%, 61.90% respectively） was much higher than that of AML other subtypes （P 〈 0.05 ）, and the longest remission period lasted for 4 years; （2） for MDS patients treated with priming chemotherapy, the total remission was 60. 87% （ CR 45.65% ,PR 15.22% ）, which was also significantly higher than that of patients received routine chemo- therapy （P 〈 0.05 ） ; （3） in comparison with patients received standard GHA priming regimen, the remission rate of com- bined priming c

关 键 词：预激化疗 急性髓系白血病 骨髓增生异常综合征 B7.1共刺激分子 

分 类 号：R733.71[医药卫生—肿瘤]