成人急性髓系白血病患者获得早期治疗反应的影响因素分析  

Factors associated with early treatment response in adults with acute myeloid leukemia

作　　者：任欣[1] 赵婷[1] 王婧[1] 主鸿鹄[1] 江浩[1] 贾晋松[1] 杨申淼[1] 江滨[1] 王德炳[1] 黄晓军[1] 江倩[1] 

机构地区：[1]北京大学人民医院、北京大学血液病研究所,100044

出　　处：《中华血液学杂志》2017年第10期869-875,共7页Chinese Journal of Hematology

摘　　要：目的探讨成人急性髓系白血病（AML）患者获得早期治疗反应的影响因素。方法回顾北京大学人民医院收治的成人AML（非急性早幼粒细胞白血病）连续病例，分析诊断时疾病特征和诱导治疗方案对患者化疗后获得形态学无白血病状态（MLFS）、首次获得MLFS时血细胞恢复程度和微小残留病[MRD，阳性定义为实时荧光定量PCR检测WT1 mRNA≥0．6％（本院正常值上限）和（或）流式细胞术发现残留白血病细胞]的影响。结果739例AML患者中，男406例（54．9％），中位年龄42（18—65）岁。在721例可评估患者中，477例（66．2％）第1个疗程诱导治疗后获MLFS，592例（82．1％）≤2个疗程获MLFS，634例（87．9％）最终获MLFS。634例患者中，首次达MLFS时，534例（84．2％）达完全缓解（CR，MLFS伴ANC≥1×10^9／L和PLT≥100×10^9／L），100例（15.8％）达CRi（MLFS伴ANC或PLT未恢复）。在566例获得MLFS并检测了MRD的患者中，260例（45．9％）MRD阳性。多因素分析显示：女性、SWOG危险度为低危、采用IA10或HAA／HAD作为诱导治疗方案是有利于第1个和≤2个疗程诱导化疗后获MLFS的共同因素。此外，骨髓原始细胞比例低、HGB高、PLT低、NPM1^＋ FLT3-ITD^-有利于第1个疗程诱导治疗后获MLFS，FLT3-ITD^-有利于≤2个疗程诱导治疗获MLFS。诊断时PLT高、采用IA10、IA8或HAA／HAD为诱导治疗方案与达CR显著相关；女性、FLT3-ITD^-、NPM1^＋FLT3-ITD^-、SWOG危险度为低危与MRD阴性显著相关。结论对于成人AML患者，女性、良好的分子或细胞遗传学特征和标准剂量诱导治疗方案是有利于早期获得高比例、深层治疗反应的因素。Objective To explore the factors influencing early treatment responses in adult with de novo acute myeloid leukemia （AML）. Methods Data of consecutive newly-diagnosed AML （non-acute promyelocytic leukemia） adults were analyzed retrospectively. To assess the impact of clinical characteristics at diagnosis and induction regimen on achieving morphologic leukemia-free state （MLFS） , blood counts and minimal residual leukemia （MRD, positive MRD defined as RQ-PCR WT1 mRNA ≥ 0.6% and/or any level of abnormal blast population detected by flow cytometry） at the time of achieving MLFS. Results 739 patients were included in this study. 406（54.9%） patients were male, with a median age of 42 years （range, 18-65 years）. In the 721 evaluable patients, MLFS was achieved in 477（66.2%） patients after the first induction regimen and 592 （82.1%） within two cycles. A total of 634 patients （87.9%） achieved MLFS, including 534 （84.2%） achieving a complete remission （CR, defined as MLFS with ANC ≥ 1 ×10^9/L and PLT ≥ 100 ×10^9/L）, 100 （ 15.8% ） achieving a CRi （defined as MLFS with incomplete ANC or PLT recovery）, respectively. 260 （45.9%） patients of 566 （89.3%） who detected MRD at the time of achieving MLFS had positive MRD. Multivariate analyses showed that female gender, favorable-risk of SWOG criteria, IA10 and HAA/HAD as induction regimen were factors associated with achieving early MLFS. In addition, low bone marrow blasts, HGB ≥ 80 g/L, PLT counts 〈 30 ×10^9/L and mutated NPM1 without FLT3-ITD were factors associated with achieving MLFS after the first induction regimen; Negative FLT3-ITD mutation was factor associated with achieving MLFS within two cycles. PLT counts ≥30 ×10^9/L and IA10, IA8 or HAA/HAD as induction chemotherapy were factors associated with achieving CR. Female gender, favorable-risk of SWOG criteria, FLT3-ITD mutation negative, mutated NPM1 without FLT3-ITD were factors associated with negative MRD. Conclusions Female gender, favorable

关 键 词：白血病 髓系 急性 形态学无白血病状态 早期治疗反应 

分 类 号：R733.71[医药卫生—肿瘤]