Ren X, Zhao T, Wang J, Zhu H H, Jiang H, Jia J S, Yang S M, Jiang B, Wang D B, Huang X J, Jiang Q
Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China.
Zhonghua Xue Ye Xue Za Zhi. 2017 Oct 14;38(10):869-875. doi: 10.3760/cma.j.issn.0253-2727.2017.10.009.
To explore the factors influencing early treatment responses in adult with de novo acute myeloid leukemia (AML) . 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. 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. Female gender, favorable molecular markers or cytogenetics, and standard-dose induction regimen were key factors associated with higher probability of early and deep responses in adults with AML.
探索影响初发急性髓系白血病（AML）成年患者早期治疗反应的因素。对连续新诊断的AML（非急性早幼粒细胞白血病）成年患者的数据进行回顾性分析。为评估诊断时的临床特征和诱导方案对达到形态学无白血病状态（MLFS）的影响，以及达到MLFS时的血细胞计数和微小残留白血病（MRD，阳性MRD定义为RQ-PCR WT1 mRNA≥0.6%和/或流式细胞术检测到任何水平的异常原始细胞群）。本研究纳入739例患者。406例（54.9%）患者为男性，中位年龄42岁（范围18 - 65岁）。在721例可评估患者中，477例（66.2%）患者在首次诱导方案后达到MLFS，592例（82.1%）在两个周期内达到。共有634例（87.9%）患者达到MLFS，其中534例（84.2%）达到完全缓解（CR，定义为MLFS且中性粒细胞绝对值≥1×10⁹/L和血小板≥100×10⁹/L），100例（15.8%）达到CRi（定义为MLFS但中性粒细胞或血小板未完全恢复）。在达到MLFS时检测MRD的566例患者中，260例（45.9%）患者MRD呈阳性。多因素分析显示，女性、SWOG标准的低危风险、IA10以及HAA/HAD作为诱导方案是与早期达到MLFS相关的因素。此外，低骨髓原始细胞比例、血红蛋白≥80 g/L、血小板计数<30×10⁹/L以及NPM1突变而无FLT3-ITD是与首次诱导方案后达到MLFS相关的因素；FLT3-ITD突变阴性是与两个周期内达到MLFS相关的因素。血小板计数≥30×10⁹/L以及IA10、IA8或HAA/HAD作为诱导化疗是与达到CR相关的因素。女性、SWOG标准的低危风险、FLT3-ITD突变阴性、NPM1突变而无FLT3-ITD是与MRD阴性相关的因素。女性、良好的分子标志物或细胞遗传学特征以及标准剂量诱导方案是与AML成年患者早期和深度反应概率较高相关 的关键因素。
